Genomic Alterations of Signaling and DNA Damage Repair Pathways in Non-Muscle Invasive Bladder Cancer.

The aim of the study was to demonstrate the most common genetic alterations and evaluate possible targets involving phosphatidylinositol-3-OH kinase (PIK3)/AKT/mammalian target of rapamycin (mTOR) signaling and DNA damage repair (DDR) pathways for personalized treatment in patients with non-muscle invasive bladder cancer (NMIBC). Alterations of these pathways were observed in 89.5% and 100% of patients, respectively. Among them, BARD1 was more frequently altered in low/intermediate-risk cases, but PARP4 was more frequently affected in intermediate/high-risk patients. The possible target feasibility of BARD1 and PARP4 alterations should be evaluated for personalized treatment using PARP-inhibitors in NMIBC. It is important to detect high tumor mutation burden (TMB) in patients in terms of immunotherapy.

A candidate antineoplastic herbal agent for bladder cancer: Ankaferd Blood Stopper.

BACKGROUND AND AIMS: Ankaferd Blood Stopper (ABS) was used for in vitro studies of osteosarcoma and colon carcinoma cancer cell lines to reveal the apoptotic and antineoplastic effects. The aim of this study is to evaluate the antineoplastic effect of ABS on bladder cancer cell cultures. METHODS: We prospectively collected minimum 0.5 cm parts of fresh frozen tumour samples from patients with bladder tumour from 2015 to 2017. Primary bladder cancer cultures were produced from the frozen tumour samples. Two different doses of ABS were used on cancer cell cultures. Viability tests of each cell cultures were performed. Flow cytometry was used for the determination of apoptosis and necroptosis. We also checked the effect of ABS on different stages, grade and variant histology of bladder cancer cells. The results of all cancer cell cultures were compared with their own controls. RESULTS: This study included 24 patients. Mean age of patients was 66.2 ± 11.7 years (34-83 years), where 19 of them (79.5%) were males and five (20.5%) were females. When we compared the data, we found decreased cancer cell viability ratio in each ABS group compared with their own controls. Necroptosis was observed in the great majority of ABS groups, and necroptosis and apoptosis were observed in some cell cultures. CONCLUSIONS: In this study, we demonstrated the cytotoxic effect of ABS on bladder cancer cells. The results of this study suggests planning of animal model of bladder cancer for ABS with intravesical application as an antineoplastic agent. In the future, ABS may be a candidate intravesical treatment agent for bladder cancer.

Anna Karenina principle in personalized treatment of bladder cancer according to oncogram: which drug for which patient?

Aim: To evaluate the ex vivo efficacy of chemotherapy, immunotherapy and targeted agents with the oncogram method in patients with bladder cancer and determine the most appropriate personalized treatment agent using immune markers. Materials & methods: Bladder cancer tissues were obtained from each patient. After cultivation, cell cultures were divided into 12 groups for each patient and 11 drugs were administered. Cell viability and immunohistochemistry expression were examined. Results: A good response rate was determined to be a 23% viability drop. The nivolumab good response rate was slightly better in PD-L1-positive patients and the ipilimumab good response rate was slightly better in tumoral CTLA-4-positive cases. Interestingly, the cetuximab response was worse in EGFR-positive cases. Conclusion: Although good responses of drug groups after their ex vivo application by using oncogram were found to be higher than control group, this outcome differed on a per patient basis.

Bladder cancer primary cell cultures were shown to be effective for drug sensitivity and also able to be used ex vivo in the process of determining personalized treatment. The ex vivo efficacy of 11 different agents was evaluated with oncogram in bladder cancer cell cultures obtained from patients. Together with clinicopathological features, evaluation of drug responses detected by oncogram can provide important information for pretreatment drug selection when deciding on individualized treatment.

The giant calculus within the prostatic urethra.

The giant calculus within the prostatic urethra is a rare clinical entity in the young population. Most of the calculi within the urethra migrate from the urinary bladder and obliterate the urethra. These stones are often composed of calcium phosphate or calcium oxalate. The decision of treatment strategy is affected by the size, shape and position of the calculus and by the status of the urethra. If the stone is large and immovable, it may be extracted via the perineal or the suprapubic approach. In most cases, the giant calculi were extracted via the transvesical approach and external urethrotomy. Our case is the biggest prostatic calculus, known in the literature so far, which was treated endoscopically by the combination of laser and the pneumatic lithotriptor.

Assessment of ex-vivo efficacy (oncogram) of immunotherapeutic and chemotherapeutic agents in bladder cancer: A pilot study of personalized treatment.

PURPOSE: To investigate the ex-vivo efficacy of immunotherapeutics and chemotherapeutics in bladder cancer primary cell cultures, to assess the applicability of the method according to the results and to evaluate suitability of the oncogram method for personalized treatment of bladder cancer. METHODS: After receiving ethics committee approval, tumor tissue was obtained from patients with transurethral resection performed due to bladder tumor from 2015 to 2017. Primary culture was produced from the obtained fresh tissue. Each culture was divided into 6 groups. The control group had only medium applied, while the other groups had Bacillus Calmette Guerin (BCG), Interferon-α (IFN-α), Gemcitabine, BCG+IFN-α and BCG+Gemcitabine, respectively. Viability tests in the 24th hour were performed on each culture. The results of all cases were compared with their own controls. Also, results of each case were compared between the cases with similar pathologic results. RESULTS: The study assessed 24 bladder cancer cases. Mean patient age was 66.2±11.7 years (34-83), with 19 male (79.5%) and 5 female patients (20.5%). When data were compared between the groups, viability percentages were 31.2%, 30.9%, 27.7%, 32.1% and 29.4% in the BCG, IFN-α, Gemcitabine, BCG+IFN-α and BCG+Gemcitabine groups compared with their own controls (73.1%), respectively (p<0.001). In addition, we found that viability results were not similar in all cases. CONCLUSIONS: Cell cultures produced from bladder cancer tissue might help to determine sensitivity to treatment. This ex-vivo method (oncogram) is a simple and applicable method that can be used for personalized treatment before intravesical or systemic therapy.

Partial nephrectomy vs. radical nephrectomy for stage I renal cell carcinoma in the presence of predisposing systemic diseases for chronic kidney disease.

Aim of this study is to compare the effects of partial nephrectomy (PN) and radical nephrectomy (RN) for stage I renal cell carcinoma (RCC) on renal functions in patients with diabetes mellitus (DM) and/or hypertension (HT). Charts of patients who underwent surgery for stage I RCC in our department were retrospectively reviewed and patients with DM and/or HT were enrolled. Preoperative and postoperative estimated glomerular filtration rates (eGFR) were calculated according to the Modification of Diet in Renal Disease (MDRD) formulation for both RN and PN groups. Groups were compared for patient demographics, preoperative eGFR, postoperative eGFR and ΔeGFR [(preoperative eGFR) - (postoperative eGFR)] which reflects the renal functional loss. There were 85 patients in the RN and 33 patients in the PN groups. Demographic data were similar but the patients in the PN group had smaller tumor size compared to RN group (32.2 ± 11.8 mm vs 47.1 ± 15.2 mm, p < 0.001). Preoperative eGFR did not differ between groups (75 ± 28.4 mL/min/1.73 m2 vs 75.5 ± 23.8 mL/min/1.73 m2 in RN and PN groups, p = 0.929). However, there were significant differences between groups in terms of postoperative eGFR (57.5 ± 21.7 mL/min/1.73 m2 vs 74 ± 27.5 mL/min/1.73 m2 in RN and PN groups, p < 0.001) and ΔeGFR (17.5 ± 4.2 mL/min/1.73 m2 vs 1.5 ± 0.4 mL/min/1.73 m2 in RN and PN groups, p < 0.001). Our findings favor the use of PN over RN for stage I RCC whenever feasible in patients with predisposing systemic diseases for chronic kidney disease for better preservation of renal functions.

Analysis of NKX3.1 expression in prostate cancer tissues and correlation with clinicopathologic features.

This study aimed to analyze NKX3.1 expression in tissue samples of benign prostate hyperplasia (BPH) and in three different prostate cancer categories. The correlation of NKX3.1 expression with clinical and pathologic features of patients having undergone radical prostatectomy also was investigated. NKX3.1 expression was determined in tissue samples obtained from four different histopathological categories: (1) from patients treated with transurethral prostatectomy for BPH (n = 26), (2) localized prostate cancer patients subjected to radical prostatectomy (n = 38), (3) biopsy samples from prostate cancer patients who were metastatic at the initial admission (n = 10), and (4) tissue samples of prostate cancer patients administered antiandrogens, but who had undergone transurethral prostatectomy for infravesical obstruction (n = 11). Standard immunohistochemical staining was performed using an antiserum raised against recombinant human NKX3.1. Staining was seen in all categories of prostatic tissues. Immunohistochemistry staining scores were lower in prostate cancer patients. The staining scores were significantly higher in patients with BPH compared to metastatic or localized prostate cancer patients. Staining scores of patients with BPH and of those under antiandrogen therapy were similar. No significant correlation was found between NKX3.1 expression and tumor volume, Gleason sum scores, the presence of extraprostatic extension, tumor stage, or serum PSA. NKX3.1 expression is significantly decreased in prostate cancer patients when compared to BPH. However, the decline of NKX3.1 expression was not correlated with prostate cancer progression and was not associated with advanced stage. Thus, NKX3.1 expression is not a clinically valuable prognostic factor.

Clinical Behavior of Bladder Urothelial Carcinoma in Young Patients: A Single Center Experience.

Background. There is not enough evidence about clinical behavior of bladder cancer in younger patients. Objective. We aimed to evaluate the clinical characteristics and prognosis of bladder urothelial carcinoma patients under the age of 40 years. Methods. Medical records of patients listed in our cancer database were retrospectively reviewed. A total of 40 patients who were initially diagnosed with bladder urothelial carcinoma at the age less than 40 years were included in the study. Patients' records were reviewed for recurrence and progression rates, demographic data, medical history, and treatment modalities. Results. Pathological results revealed 33 (82.5%) Ta low-grade, 6 (15%) T1 high-grade, and 1 (2.5%) T2 high-grade urothelial carcinomas. Recurrence was detected in 14/39 (35.9%) patients but progression was not observed in any patients. The mean age of recurrent patients was significantly higher than nonrecurrent patients (34.8 versus 28.5 years; p < 0.05). Besides, recurrence was detected in only 1 patient with the age under 30 years (6.2%) and 13 patients (54.1%) between 30 and 40 years old, respectively (p < 0.05). Conclusion. Bladder urothelial carcinoma diagnosed at young age tends to be a low pathologic stage, with relatively low rate of recurrence and progression.

Vascular endothelial growth factor expression in untreated and androgen-deprived patients with prostate cancer.

The aim of the study was to investigate immunohistochemically the expression of vascular endothelial growth factor (VEGF) in untreated and androgen-deprived patients with prostate cancer. The study included 20 patients with prostate cancer who had undergone transurethral prostatectomy due to infravesical obstruction. All patients had been receiving androgen deprivation therapy for at least 3 months. Transurethral prostatectomy specimens were examined for VEGF expression after androgen deprivation, and the biopsy samples of the same patients were used for the evaluation of VEGF expression before androgen deprivation. VEGF expression was analyzed using immunohistochemistry. Staining patterns determined by the staining scores were compared before and after treatment. The correlation of VEGF expression with PSA, Gleason score, and the percent change in PSA after treatment was also investigated. Eligible biopsy specimens were available in 15 of the 20 patients, allowing for the evaluation of VEGF expression before treatment. All prostate cancer specimens were positive. VEGF was localized mainly in the cytoplasm or on the membrane of carcinoma cells. Staining was strong in 86.7% of patients before androgen deprivation. Heterogeneous staining (strong in 25%, moderate in 35%, and weak in 40%) was observed after treatment. Staining scores were significantly higher in patients before androgen deprivation and showed a significant decrease after androgen deprivation (p = 0.007). Tumor staining correlated with Gleason score. No significant correlation was determined between VEGF expression and pre-treatment PSA and percent change of PSA after treatment. Immunohistochemical results indicate that VEGF expression is downregulated by androgen deprivation therapy. VEGF may be a potential target for therapeutic intervention in prostate cancer.

The value of PSA, free-to-total PSA ratio and PSA density in the prediction of pathologic stage for clinically localized prostate cancer.

OBJECTIVE: The ability of prostate-specific antigen (PSA), free/total PSA and PSA density to predict the pathologic stage in prostate cancer has not been clear yet. In this study, we evaluated the value of PSA subgroups in the prediction of pathologic stage after radical prostatectomy. METHODS: A total of 42 subjects 55-78-years-old who underwent radical retropubic prostatectomy were included in the study. Preoperative PSA, free/total PSA and PSA density (PSAD) values were compared according to the pathologic stages of radical prostatectomy specimens. Receiver operating characteristics (ROC) curves were measured for each parameter. RESULTS: The clinical stage that was estimated for all patients was between T1N0M0 and T2bN0M0. Pathologic examination revealed organ-confined disease in 18 patients. The area under curve (AUC) for organ confinement was 0.553 for PSA, 0.446 for free/total PSA ratio and 0.706 for PSAD. Cut-off values providing the best sensitivity and specificity in ROC analysis for PSA, free/total PSA and PSAD were 7.1, 0.15, and 0.17, respectively (likelihood ratio: 0.9, 1 and 2). The positive predictive values at these cut-off values were 0.54, 0.56, and 0.70, respectively. Only PSAD cut-off values was found statistically borderline significant for predicting organ-confined disease. CONCLUSION: While PSAD is more helpful than PSA and free/total PSA ratio for prediction of organ-confined disease, none of these parameters are significant predictor of pathologic stage for clinically localized prostate cancer.

Evaluation of computed tomography findings for success prediction after extracorporeal shock wave lithotripsy for urinary tract stone disease.

PURPOSE: Currently, the most widely used method of treatment of urinary tract stones is extracorporeal shock wave lithotripsy (SWL). Patient and stone characteristics are important for SWL success. We evaluated noncontrast computed tomography (NCCT) characteristics of urinary tract stones for the prediction of SWL success. METHODS: Records of patients who underwent NCCT before SWL treatment between January 2008 and June 2012 were retrospectively evaluated. Demographic data were recruited from patient files. Hounsfield units (HU), stone size and skin-to-stone distance (SSD) were measured on NCCT. After serial measurements of the highest HU value (HUmax) and lowest HU value (HUmin), HU value was calculated as the average of these two values (HUave). These parameters were compared between successful [stone-free (SF) group] and unsuccessful [residual fragment (RF) group] cases after SWL. RESULTS: A total of 254 patients, 113 kidney stones and 141 ureteral stones, were evaluated. Mean age was 51.0±14.6 (18-87) years, and mean stone size was 10.9±3.7 mm. Stone diameter, HUmax, HUmin and HUave were significantly lower in SF group when compared with RF group for both kidney and ureteral stones (p<0.05). We also found that SSD for kidney stones was predictive for SWL success. CONCLUSIONS: We suggest that HUmax, HUmin and HUave values are significant predictors of SWL success for both kidney and ureteral stones. They might be used in daily clinical practice for patient counselling.

Ascites following prostatectomy: a rare presentation of comorbid disease.

We report a rare case of ascites developing in the early post-prostatectomy period due to a mass originating from the head of the pancreas. Comorbid diseases that are not documented preoperatively may emerge with signs mimicking the complication of prostate surgery.

Increased expression of NKX3.1 in benign prostatic hyperplasia.

OBJECTIVES: To establish the role of the NKX3.1 gene in the development of benign prostatic hyperplasia by comparing the expression of NKX3.1 in messenger ribonucleic acid (mRNA) and protein levels in young adult prostate and BPH tissues. METHODS: Normal prostate tissue samples (n = 4) were obtained from prostate biopsies of patients less than 40 years of age who underwent diagnostic cystoscopy for microscopic hematuria. Benign prostatic hyperplasia tissues (n = 12) were obtained from patients who underwent transurethral prostate resection for bladder outlet obstruction. The RNAs isolated from these tissue samples were analyzed with quantitative reverse transcriptase polymerase chain reaction; the proteins were analyzed with Western blotting and immunohistochemistry. RESULTS: The mean NKX3.1 mRNA transcript expression was 19.17 +/- 3.05 vs 1.24 +/- 1.32 in BPH and normal tissues, respectively, and NKX3.1 protein expression of BPH was approximately 2.4-fold higher than in normal prostate tissue. Reverse transcriptase polymerase chain reaction and Western blot analyses revealed that NKX3.1 gene expression in BPH patient tissues were higher compared with normal prostate tissues. Immunohistochemistry results indicated that most of the BPH tissues stained diffusely, and there was no BPH tissue that lacked NKX3.1 expression. CONCLUSIONS: NKX3.1 expression is elevated in BPH tissues when compared with normal tissues, which may be important in the development of BPH.

Relation between acute urinary retention, chronic prostatic inflammation and accompanying elevated prostate-specific antigen.

OBJECTIVE: To determine if there is a relationship between acute urinary retention (AUR), the prostate-specific antigen (PSA) level and chronic inflammation of the prostate. We therefore studied patients with benign prostatic obstruction (BPO) with (n = 64) or without (n = 168) acute urinary retention (AUR) who underwent transurethral resection of the prostate (TURP) in a retrospective case control study. MATERIAL AND METHODS: Between 2001 and 2004, a total of 232 patients underwent TURP due to BPO with or without AUR. The mean values of age, prostate volume, weight of resected prostate and PSA level and the histopathologic results of patients with and without AUR were compared. Chi(2) analysis was used to examine the relationship between prostatic inflammation and AUR. The contribution of each variable to AUR was assessed by means of multiple linear regression. RESULTS: A total of 64 patients (28%) were operated on for AUR due to BPO. There were no statistical differences between patients with or without AUR with respect to the mean values of PSA, percent free PSA, prostate size or weight of the resected prostate tissue. Elevated PSA values (>or=4.0 ng/ml) were detected in 64% and 38% of the patients in the AUR and non-AUR groups, respectively (p = 0.01). Histopathological re-evaluation demonstrated that chronic prostatic inflammation was present in 56% and 37% of the specimens in the AUR and non-AUR groups, respectively (p = 0.014). In the AUR group, the mean PSA level was significantly higher in patients with than without prostatic inflammation (7.75+/-5.26 vs 5.07+/-3.21 ng/ml; p = 0.022). The odds ratio of AUR for patients with chronic prostatic inflammation and elevated PSA was determined as 4.14 (95% CI 1.65-10.41). Multiple linear regression revealed that prostatic inflammation made a significant contribution to AUR. CONCLUSIONS: Chronic prostatic inflammation may be histopathological evidence of both elevated PSA level and AUR; hence it may play a role in the pathophysiology of AUR.

Diclofenac suppository administration in conjunction with lidocaine gel during transrectal ultrasound-guided prostate biopsy: prospective, randomized, placebo-controlled study.

OBJECTIVES: To evaluate the additional analgesic efficacy of the rectal administration of diclofenac suppository compared with placebo in patients undergoing transrectal ultrasound-guided prostate biopsy. METHODS: A total of 40 consecutive men undergoing biopsy were enrolled in this study. Patients were randomized equally into two treatment groups. In group 1, patients received an intrarectal 100-mg diclofenac suppository 1 hour before biopsy. In group 2, patients received a glycerin suppository as a placebo intrarectally 1 hour before biopsy. All patients received 10 mL of 2% lidocaine gel intrarectally 10 minutes before biopsy. A self-administrated visual analog scale was used to measure the pain scores at the end of the biopsy and 2 hours and 1 day after the biopsy. RESULTS: The mean patient age was 63.3 +/- 6.8 years and 61.6 +/- 6.7 years in groups 1 and 2, respectively. The mean pain score in groups 1 and 2 was 3.4 +/- 1.3 versus 5.9 +/- 1.7 (P < 0.0001), respectively, at the end of the biopsy. The mean pain score at 2 hours and 1 day after the procedure was 1.2 +/- 1.0 versus 3.6 +/- 1.4 (P < 0.0001) and 0.5 +/- 0.9 versus 1.4 +/- 1.3 (P = 0.017) in groups 1 and 2, respectively. CONCLUSIONS: Intrarectal diclofenac suppository administration is a simple, safe, and effective procedure to reduce pain and improve patients' tolerance of transrectal ultrasound-guided prostate biopsy. We recommend intrarectal diclofenac suppository administration, together with intrarectally administered lidocaine gel, in men undergoing transrectal ultrasound-guided prostate biopsy.

Echo contrast-enhanced power Doppler ultrasonography for assessment of angiogenesis in renal cell carcinoma.

OBJECTIVE: Tumoral growth is an angiogenesis-dependent event. Although there are studies about the importance of histopathologic angiogenesis in various malignancies, the assessment of the angiogenesis by radiologic techniques is not well established. The aim of this study was to investigate the efficacy of echo contrast-enhanced power Doppler ultrasonography (PDUS) in determining the angiogenic status of renal cell carcinoma (RCC). METHODS: Power Doppler ultrasonography was performed before and after intravenous administration of an echo contrast agent in 42 patients with renal masses. Twenty-one of these renal masses were diagnosed as RCC histopathologically, and these 21 patients were reevaluated retrospectively. The color pixel ratios of selected images were calculated as the ratio of the number of pixels showing power Doppler signals to the total number of pixels within the lesion. The results were compared with the histopathologic microvessel density (MVD). RESULTS: A significant correlation was found between color pixel ratio and MVD values in both PDUS techniques. The use of the echo contrast agent improved this correlation and P values (Spearman rho from 0.436 to 0.551; P from .048 to .01). CONCLUSIONS: Color pixel ratio values reflect the MVD in RCC. Therefore, these results suggest that preoperative quantification of angiogenesis can be possible with the help of PDUS in RCC.

Development of vesical calculi following tension-free vaginal tape procedure.

We present a case of a bladder stone that had formed around the intravesical portion of tension-free vaginal tape (TVT) material following unnoticed bladder perforation during the procedure. Endoscopic lithotripsy of the bladder calculi was performed and the TVT sling material was removed by an endoscopic approach. High clinical suspicion of bladder complications is necessary when evaluating patients presenting with urinary symptoms after a TVT procedure.

Thrombosis and priapism in a patient with Henoch-Schonlein purpura.

Henoch-Schönlein purpura (HSP) belongs to the category of systemic small-vessel vasculitis. Although long-term outcome is generally good, serious complications may occur. Thrombosis and priapism have been reported only as extremely rare complications of HSP. We describe a 37-year-old man who developed recurrent thrombotic events shortly after he had been diagnosed as having HSP. Although he had additional risk factors for thrombosis, such as prothrombin G20210A mutation and use of celecoxib before the last episode, temporal relation of the thrombotic attacks to the onset of HSP suggest that the disease itself may lead to a prothrombotic state. This case is the first adult HSP patient with priapism, which probably developed secondary to thrombosis of the dorsal penile vein.

Early catheter removal following transurethral prostatectomy: overnight catheterization.

OBJECTIVE: Our aim was to determine the safety and feasibility of catheter removal on the first morning after transurethral prostatectomy. METHODS: Fifty-four patients who underwent transurethral prostatectomy were included in a prospective study. The decision to remove the catheters on the first morning after surgery was based on the color of the catheter effluent, absence of clots, normal vital signs and adequate urine output. Patients who voided successfully were discharged on the same day as catheter removal. RESULTS: Catheters were removed in 43 (79.6%) patients on postoperative day 1. Of these patients 40 (93%) voided successfully, however 3 of them required recatheterization due to bleeding or urinary retention. The criteria for catheter removal were not met in 11 patients and their catheters were removed on postoperative day 2 in 2 and on postoperative day 3 in 9. The mean length of hospital stay after surgery was 1.74 days for the entire group and 1.41 days for those in whom the catheter was removed on postoperative day 1. CONCLUSION: Overnight catheterization after transurethral prostatectomy seems to be a feasible approach without leading to significant morbidity in selected patients.