Quality of Life in Patients with High-grade Non-muscle-invasive Bladder Cancer Undergoing Standard Versus Reduced Frequency of Bacillus Calmette-Guérin Instillations: The EAU-RF NIMBUS Trial.

Background: Adverse events induced by intravesical bacillus Calmette-Guérin (BCG) to treat high-grade non-muscle-invasive bladder cancer (NMIBC) often lead to treatment discontinuation. The EAU-RF NIMBUS trial found a reduced number of standard-dose BCG instillations to be inferior with the standard regimen. Nonetheless, it remains important to evaluate whether patients in the reduced BCG treatment arm had better quality of life (QoL) due to a possible reduction in toxicity or burden. Objective: To evaluate whether patients in the EAU-RF NIMBUS trial experienced better QoL after a reduced BCG instillation frequency. Design setting and participants: A total of 359 patients from 51 European sites were randomized to one of two treatment arms between December 2013 and July 2019. The standard frequency arm (n = 182) was 6 weeks of BCG induction followed by 3 weeks of maintenance at months 3, 6, and 12. The reduced frequency arm (n = 177) was BCG induction at weeks 1, 2, and 6, followed by maintenance instillations at weeks 1 and 3 of months 3, 6, and 12. Outcome measurements and statistical analysis: Analyses were performed using an intention-to-treat analysis and a per-protocol analysis. QoL was measured using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 version 3.0 (QLQ-C30 v.03) prior to the first and last instillations of each BCG cycle. Group differences were determined using linear regression corrected for QoL at baseline. Differences in QoL over time were tested for significance using a linear mixed model. Side effects were recorded by the treating physician using a standardized form. Chi-square tests were used to compare the side-effect frequency between the arms. Results and limitations: There were no significant differences in the means of each QoL scale between the two arms. There were also no significant changes over time in all QoL domains for both arms. However, differences in the incidence of general malaise at T1 (before the last induction instillation), frequency, urgency, and dysuria at T7 (before the last maintenance instillation) were detected in favor of the reduced frequency arm. Conclusions: Reducing the BCG instillation frequency does not improve the QoL in NMIBC patients despite lower storage symptoms. Patient summary: In this study, we evaluated whether a reduction in the number of received bacillus Calmette-Guérin instillations led to better quality of life in patients with high-grade non-muscle-invasive bladder cancer. We found no difference in the quality of life between the standard and the reduced bacillus Calmette-Guérin instillation frequency. We conclude that reducing the number of instillations does not lead to better quality of life in patients with high-grade non-muscle-invasive bladder cancer.

Treatment of High-grade Non-muscle-invasive Bladder Carcinoma by Standard Number and Dose of BCG Instillations Versus Reduced Number and Standard Dose of BCG Instillations: Results of the European Association of Urology Research Foundation Randomised Phase III Clinical Trial "NIMBUS".

BACKGROUND: Intravesical instillation of bacillus Calmette-Guérin (BCG) is an accepted strategy to prevent recurrence of non-muscle-invasive bladder cancer (NMIBC) but associated with significant toxicity. OBJECTIVE: NIMBUS assessed whether a reduced number of standard-dose BCG instillations are noninferior to the standard number and dose in patients with high-grade NMIBC. DESIGN, SETTING, AND PARTICIPANTS: A total of 345 patients from 51 sites were randomised between December 2013 and July 2019. We report results after a data review and safety analysis by the Independent Data Monitoring Committee based on the cut-off date of July 1, 2019. INTERVENTION: The standard BCG schedule was 6 wk of induction followed by 3 wk of maintenance at 3, 6, and 12 mo (15 instillations). The reduced frequency BCG schedule was induction at wks 1, 2, and 6 followed by 2 wk (wks 1 and 3) of maintenance at 3, 6, and 12 mo (nine instillations). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was time to first recurrence. Secondary endpoints included progression to ≥ T2 and toxicity. RESULTS AND LIMITATIONS: In total, 170 patients were randomised to reduced frequency and 175 to standard BCG. Prognostic factors at initial resection were as follows: Ta/T1: 46/54%; primary/recurrent: 92/8%; single/multiple: 57/43%; and concomitant carcinoma in situ: 27%. After 12 mo of median follow-up, the intention-to-treat analysis showed a safety-relevant difference in recurrences between treatment arms: 46/170 (reduced frequency) versus 21/175 patients (standard). Additional safety analyses showed a hazard ratio of 0.40 with the upper part of the one-sided 97.5% confidence interval of 0.68, meeting a predefined stopping criterion for inferiority. CONCLUSIONS: The reduced frequency schedule was inferior to the standard schedule regarding the time to first recurrence. Further recruitment of patients was stopped immediately to avoid harm in the reduced frequency BCG arm. PATIENT SUMMARY: After surgical removal of the tumour, patients with high-grade non-muscle-invasive bladder cancer are treated with bacillus Calmette-Guérin to prevent recurrence and progression. This is associated with significant side effects. We report the results of a clinical trial showing a reduction in the number of instillations (from 15 to nine in total) being inferior to the standard protocol. From today's perspective, complete tumour resection and a standard number of instillations remain the standard of care.

International and Multi-institutional Assessment of Factors Associated With Performance and Quality of Lymph Node Dissection During Radical Nephrectomy.

OBJECTIVE: To determine factors associated with performance and quality of lymph node dissection during radical nephrectomy. MATERIALS AND METHODS: Using an International Data Registry, we performed multilevel logistic regression to determine the association of surgical approach (open surgery vs minimally invasive surgery), institutional experience (low, moderate, and high tertiles), and institutional preference (minimally invasive surgery, balanced, and open surgery tertiles) with the performance of lymph node dissection in subgroups by clinical stage and nodal status. RESULTS: Among 1,742 patients undergoing radical nephrectomy, 312 (18%) underwent lymph node dissection, which was associated with stage (28% for ≥cT2 vs 9.3% for cT1), and nodal status (68% for ≥cN1 vs 13% for cN0). Open surgery was significantly associated with performing lymph node dissection in all subgroups. Institutional experience and institutional preference had no association with performing lymph node dissection in the ≥cN1 group. The number of nodes removed was greater for open surgery (mean 5.9) vs minimally invasive surgery (mean 3.4); this held true even when stratified by stage and nodal status. CONCLUSION: In this large dataset, open surgical radical nephrectomy is associated with more frequent performance and higher quality of lymph node dissection, which may owe to selection bias but also could reflect technical concerns. In the patient population in whom lymph node dissection is recommended (≥cN1), this is not explained by institutional experience or preference. Lymph node dissection may be under-utilized for ≥cN1 disease and over-utilized for cN0 disease, at least according to practice guidelines.

Ischemia modified albumin: does it change during pneumoperitoneum in robotic prostatectomies?

BACKGROUND: The unique positioning of the patient at steep Trendelenburg with prolonged and increased intra-abdominal pressure (IAP) during robotic radical prostatectomy may increase the risk of splanchnic ischemia. We aimed to investigate the acute effects of IAP and steep Trendelenburg position on the level of ischemia modified albumin (IMA) and to test if serum IMA levels might be used as a surrogate marker for possible covert ischemia during robotic radical prostatectomies. PATIENTS AND METHODS: Fifty ASA I-II patients scheduled for elective robotic radical prostatectomy were included in this investigation. EXCLUSION CRITERIA: The patients were excluded from the study when an arterial cannulation could not be accomplished, if the case had to be converted to open surgery or if the calculated intraoperative bleeding exceeded 300ml. All the patients were placed in steep (45 degrees) Trendelenburg position following trocar placement. Throughout the operation the IAP was maintained between 11-14mmHg. Mean arterial blood pressure (MAP), cardiac output (CO) were continuously monitored before the induction and throughout the surgery. Blood gases, electrolytes, urea, creatinine, alanine transferase (ALT), aspartate transferase (AST) were recorded. Additionally, IMA levels were measured before, during and after surgery. RESULTS: (1) MAP, CO, lactate and hemoglobin (Hb) did not significantly change in any period of surgery (p>0.05); (2) sodium (p<0.01), potassium (p<0.05) and urea (p<0.05) levels decreased at postoperative period, and no significant changes at creatinine, AST, ALT levels were observed in these patients; (3) At the end of surgery (180 min) pCO2, pO2, HCO3 and BE did not change compared to after induction values (p>0.05) but mild acidosis was present in these patients (p<0.01 vs. after induction); (4) IMA levels were found to be comparable before induction (0.34±0.04), after induction (0.31±0.06) and at the end of surgery (0.29±0.05) as well. CONCLUSION: We did not demonstrate any significant mesenteric-splanchnic ischemia which could be detected by serum IMA levels during robotic radical prostatectomies performed under steep Trendelenburg position and when IAP is maintained in between 11-14 mmHg.

Simple Renal Cysts: Prevalence, Associated Risk Factors and Follow-Up in a Health Screening Cohort.

PURPOSE: To investigate the prevalence of simple renal cysts in an adult health-screening cohort, and to evaluate clinical characteristics, associated risk factors and the natural course. MATERIALS AND METHODS: Between April and November 2008, a thousand individuals diagnosed with simple renal cyst by ultrasonography in a check-up program were chart-reviewed for demographic-clinical characteristics and cyst features. Follow-up was done via electronic patient records. Univariate and multivariate analyses to evaluate the relationship of outcomes and correlation analysis were done to measure the degree of association between parameters. RESULTS: The prevalence was 7.7%. There were 123 cysts in 77 patients, followed for 3.5 years (mean). Individuals with cysts were older (P < .01). Prevalence rates were 2.7% in individuals younger than 40 years and 23.9% in older than 60. The cysts were predominantly (94.8%) detected in males and most (63.6%) were solitary. No relation with Body Mass Index and total cholesterol levels was found but serum creatinine values were significantly increased in individuals with cysts (P < .01). There was no difference in the diagnosis of hypertension and microscopic hematuria in patients with renal cysts, however diabetes/hyperglycemia were more common and increasing age correlated with higher number of cysts (all P < .05). Follow-up revealed that the number of cysts were increased and/or the same in 86.5%; the sizes of cysts were larger and/or the same in 78.4% of patients, while in 14% of patients the cyst disappeared. CONCLUSION: In a cohort of adults undergoing a health-screening, the prevalence of simple renal cyst was found 7.7% by ultrasonography. Renal cysts were more common in males and elders, and associated with increased levels of serum creatinine and diabetes.

EAU Guidelines on Urethral Trauma.

CONTEXT: These guidelines were prepared on behalf of the European Association of Urology (EAU) to assist urologists in the management of traumatic urethral injuries. OBJECTIVE: To determine the optimal evaluation and management of urethral injuries by review of the world's literature on the subject. EVIDENCE ACQUISITION: A working group of experts on Urological Trauma was convened to review and summarize the literature concerning the diagnosis and treatment of genitourinary trauma, including urethral trauma. The Urological Trauma guidelines have been based on a review of the literature identified using on-line searches of MEDLINE and other source documents published before 2009. A critical assessment of the findings was made, not involving a formal appraisal of the data. There were few high-powered, randomized, controlled trials in this area and considerable available data was provided by retrospective studies. The Working Group recognizes this limitation. EVIDENCE SYNTHESIS: The full text of these guidelines is available through the EAU Central Office and the EAU website (www.uroweb.org). This article comprises the abridged version of a section of the Urological Trauma guidelines. CONCLUSIONS: Updated and critically reviewed Guidelines on Urethral Trauma are presented. The aim of these guidelines is to provide support to the practicing urologist since urethral injuries carry substantial morbidity. The diversity of urethral injuries, associated injuries, the timing and availability of treatment options as well as their relative rarity contribute to the controversies in the management of urethral trauma.

Complexed prostate specific antigen: better test in the diagnosis of prostate cancer for the clinically relevant 2.5-4 ng/ml total PSA range.

BACKGROUND: Data on utilizing complexed prostate specific antigen (cPSA) offering increased diagnostic performance over other available clinical parameters in diagnosis of prostate cancer is still controversial. Our objective was to determine diagnostic performance of cPSA compared to total prostate specific antigen (tPSA) and corresponding ratios for possible routine application. METHODS: In a prospective study including overall 315 consecutive men, 177 patients with suspicious digital rectal examination, and/or tPSA value > 2.5 ng/ml underwent prostate biopsy. Serum samples for tPSA, cPSA and free PSA were analyzed using automated chemiluminometric technology. RESULTS: Area under the curve (AUC) for cPSA, although greater, was not statistically different compared to that of tPSA (p = 0.253). AUCs of f/c, f/t and c/t ratios were all found significantly inferior. At clinically relevant 2.37 ng/ml threshold, cPSA performed with 85% sensitivity and significantly higher specificity of 63.1%, compared to same sensitivity and specificity of 57.2% at a 3.00 ng/ml cut off for tPSA. CONCLUSIONS: Utilizing automated assay systems at predetermined cut off value for cPSA we would be able to save 27.1% of the biopsies while missing 13.4% of the cancers. Therefore, results of this study indicate higher discriminatory power of cPSA in diagnosis of prostate cancer for clinically relevant 2.5-4 ng/ml tPSA range.

Erectile dysfunction following radiotherapy and brachytherapy for prostate cancer: pathophysiology, prevention and treatment.

OBJECTIVES: Although detrimental impact on sexual function following radiotherapy (RT) and brachytherapy decreases the quality of life of prostate cancer survivors, the etiology, pathophysiology, prophylaxis and treatment of this condition has not yet been fully clarified. We reviewed the published literature in terms of etiology, treatment and possible prevention of erectile dysfunction (ED) following RT and/or brachytherapy. METHOD: We have reviewed the literature through a MEDLINE search. Prostate cancer, erectile dysfunction, radiotherapy, brachytherapy, treatment and quality of life were used as keywords. CONCLUSION: Both RT and brachytherapy result in high rates of ED. Although arterial damage seems to be the main cause of ED after RT, exposure of neurovascular bundle to high levels of radiation dose has been also implicated in some studies with brachytherapy. The radiation dose received by the corpora cavernosa at the crurae of the penis may also be important in the etiology of ED. The most important predictive factor of ED following RT is the treatment modality. Intensity-modulated radiotherapy and vessel-sparing prostate radiotherapy are new techniques but those treatments may not guarantee complete preservation of the erectile function. Patients need to be correctly informed on the possible sequela of radiation-based treatments on their sexual well-being while planning their treatment. Patients should also be informed about the possible treatment modalities for ED, which may develop in due course.

The inhibitory effect of vitamin E on cigarette smoke-induced oxidative damage to the rat urothelium: can it prevent transitional cell carcinoma?

INTRODUCTION: We aimed to detect reactive oxygen species (ROS) and assess subsequent carcinogenesis in terms of cellular proliferation in the bladder and kidney epithelial tissues of rats exposed to cigarette smoke (CS), and to investigate the changes following vitamin E treatment. MATERIALS AND METHODS: Twenty-four male Sprague-Dawley rats were divided into 3 groups: group 1 was kept intact; group 2 was subjected to CS exposure for 8 weeks, and group 3 received intraperitoneal vitamin E injections (200 mg/kg/week) for 8 weeks in addition to CS exposure. Histological examination and Ki67 antigen expression measurements were made from bladder and renal pelvic tissue sections. Luminol-amplified chemiluminescence was used to measure ROS levels. All results were compared using a one-way ANOVA test. RESULTS: In CS-exposed rats, light microscopy of renal and bladder tissues revealed nonspecific epithelial changes; however, Ki67 expression was significantly increased in bladder tissues compared to other groups (17.5 +/- 4.7, 35 +/- 2.9 and 18.7 +/- 5.1% in groups 1, 2 and 3, respectively, p < 0.05). Chemiluminescence levels in bladder and renal tissues were also significantly higher in the CS-exposed animals (78.1 +/- 11.4, 148 +/- 13.3, 97.8 +/- 6.1 rlu/mg for the bladder, and 99.8 +/- 12.2, 176.1 +/- 27.9, 67.1 +/- 9 rlu/mg, for renal pelvic tissues, respectively, p < 0.05). CONCLUSIONS: Vitamin E can alleviate CS-induced oxidative damage in rat bladder and kidney epithelium suggesting a potential role for vitamin E in the prevention of CS-mediated carcinogenesis.

Large Cystitis glandularis: a very rare cause of severe obstructive urinary symptoms in an adult.

Cystitis glandularis is a very rare proliferative disorder of the mucus-producing glands within the mucosa and submucosa of urinary bladder epithelium. We report such a case of glandular cystitis with intestinal metaplasia masquerading as a bladder tumor in a young male patient who presented with severe obstructive urinary symptoms. Cystoscopy revealed a tumor well circumscribed, measuring 5 x 4 cm on the trigone. Transurethral resection of the mass was carried out and the histopathology suggested cystitis glandularis. The literature regarding this entity has been reviewed and the differential diagnosis was discussed. Short-term follow-up of the patient with sonography and cystoscopy showed no recurrence.

A new suture technique for anastomosis in radical retropubic prostatectomy and early removal of urethral catheter.

INTRODUCTION: A modified suture technique for urethro-vesical anastomosis during radical retropubic prostatectomy was developed and utilized in a cohort of patients. Comparative analysis of postoperative outcome was performed with a previous group of patients who had an anastomosis with the conventional technique. MATERIAL AND METHODS: A consecutive group of patients who underwent radical retropubic prostatectomy in our department with the diagnosis of localized prostate cancer was included in this retrospective study. Urethro-vesical anastomosis was performed either with the new or conventional method (CM). Outcome data of these two different patient sets were compared. RESULTS: One-hundred and one consecutive patients (mean age of 61.9 years) who were operated by either one of the two anastomotic suture techniques composed our study group. The mean follow-up period was 18 months (min: 12-max: 24). Urethro-vesical "U" (UVU) suture was performed in 51 patients, and CM in 50 patients. Foley catheter was removed at postoperative fourth day in 33 (64.7%) and 18 (36%) patients in UVU and CM groups, respectively (p < 0.01). Incontinence rate was significantly lower in the UVU group at postoperative first year (p < 0.0005). Anastomotic strictures were observed in only 1.9% of the cases in UVU group, compared to 4% in CM group. CONCLUSION: Outcome data from our patient group indicate that UVU suture may allow a high quality urethro-vesical anastomosis with a very favorable outcome in terms of early catheter removal, high continence and low stricture formation rates in patients undergoing radical retropubic prostatectomy. Further validation of these results requires a prospective randomized trial.

A new approach for the surgery of large renal masses: abdominal wall flap incision.

INTRODUCTION: The type of skin incision affects the course of surgery during radical nephrectomy. We investigated the efficacy of a new type of incision for the surgical approach to large renal masses. PATIENTS AND METHODS: Fourty patients (23 males and 17 females, mean age 63 years) who underwent radical nephrectomy in our department between 2002 and 2004 were evaluated. The outcomes in the groups with chevron incision and abdominal wall flap incision (AFI) were compared in terms of greatest tumor diameter, operation duration, perioperative blood loss, postoperative complications, and duration of hospitalization. Statistical analysis was made by independent-samples t test. RESULTS: Chevron incision was used in the first 15 patients, while subsequent 25 patients were operated via AFI. The operation duration was slightly longer in the AFI group (3.78 vs. 3 h); however, the mean largest tumor diameter was significantly greater in patients operated via AFI (11.3 vs. 7.4 cm, p < 0.05). The mean blood losses were 1,100 and 590 ml in the chevron incision and AFI groups, respectively (p < 0.05). There was no significant difference in terms of duration of hospitalization and postoperative morbidity. CONCLUSION: In our experience, AFI provides the best exposure and improved control of renal vessels and vena cava during radical nephrectomy and enables a safe dissection even in very large tumors with minimal blood loss.

Proximal type epithelioid sarcoma of the scrotum: a source of diagnostic confusion that needs immediate attention.

Epithelioid sarcoma is a rare soft-tissue sarcoma which classically presents as a subcutaneous or deep dermal mass in distal extremities of adolescents and young adults. A more aggressive "proximal" or "large-cell" type has been described in rare cases to occur as a deep soft-tissue mass at proximal body sites which tends to recur and metastasize earlier than the conventional epithelioid sarcoma. The correct diagnosis of this type is essential since these lesions can easily be misdiagnosed as other epithelioid lesions. Its prognostic factors also have not yet been fully investigated. We herein report a case of metastatic proximal-type epithelioid sarcoma arising from the scrotum of a 50-year-old man managed by radical surgery and adjuvant chemotherapy.

Comparison of microvessel densities in rat prostate tissues treated with finasteride, bicalutamide and surgical castration: a preliminary study.

BACKGROUND: A group of anti-androgens with different mechanisms of action and adverse effects have been investigated in patients with gross hematuria related to benign prostate hyperplasia; however, there is not yet any consensus about the standard management of these patients. The present study aims to identify if any one type of the hormonal intervention is superior in terms of the suppression of microvessel formation in the prostate. MATERIALS AND METHODS: A total of 28 mature, healthy male Sprague-Dawley rats (300 +/- 50 g) were used in this study. The rats were randomly assigned to one of four groups (n = 7 per group). The effects of three different hormonal therapies on angiogenesis and microvascularity in rat ventral prostate were compared. Groups 1 and 2 were treated for 28 days with finasteride and bicalutamide, respectively, and rats from Group 3 underwent surgical castration. Following treatment, all rats included in the study underwent dissection of the ventral prostate and immunohistochemical analysis of microvessel density by factor VIII-related antigen. RESULTS: The mean number of microvessels in the finasteride and bicalutamide groups was 24.5 (+/-8.44 SE) and 27 (+/-9.89 SE) respectively. In contrast, the castration and control groups had microvessel numbers of 12.9 (+/-5.35 SE) and 40.3 (+/-5.03 SE) respectively. Differences were statistically significant between all three treatment groups and the controls (P < 0.005); the number of microvessels in rat prostate tissues of the control group was significantly higher than the treatment groups. Mean microvessel densities in the bicalutamide and finasteride groups were significantly higher than microvessel densities in the castration group (P < 0.005). There was no statistically significant difference between mean microvessel number in rat prostate tissue treated with finasteride or bicalutamide (P > 0.05). CONCLUSIONS: Even though finasteride was not as effective as castration in reducing microvessel number, its effect was equal to that of bicalutamide in terms of suppressing the angiogenesis in prostatic tissue. Based on the findings of the present study, finasteride might offer a viable option in the management of macroscopic hematuria by inhibition of microvessel formation within the prostatic tissue. Further clinical studies are warranted.

Cervical lymph node enlargement on the right side as the initial manifestation of metastatic prostate cancer.

OBJECTIVES: Cervical lymph node enlargement (LAP) due to metastatic spread is an uncommon manifestation of prostatic adenocarcinoma. In case of non-regional lymphatic spread, left supraclavicular region was found to be the most common site (1,2,3) whereas right sided metastatic lymph node involvement has been extremely uncommon. METHODS: We here in describe a case of a 75 year-old man who had an enlarged cervical lymph node for a year which subsequently proved to be involved by metastatic adenocarcinoma of the prostate. CONCLUSIONS: Although, prostate cancer rarely metastasize to the cervical lymph node chain it should always be considered in the differential diagnosis of metastatic lymph node enlargement in the cervical area of elderly men.