Grainyhead-Like 3 Influences Migration and Invasion of Urothelial Carcinoma Cells.

Invasive urothelial carcinomas of the bladder (UCB) characteristically show a loss of differentiation markers. The transcription factor Grainyhead-like 3 (GRHL3) plays an important role in the development and differentiation of normal urothelium. The contribution to UCB progression is still elusive. Differential expression of GRHL3 was assessed in normal human urothelium and in non-invasive and invasive bladder cancer cell lines. The contribution of GRHL3 to cell proliferation, viability and invasion in UCB cell lines was determined by gain- and loss-of-function assays in vitro and in an organ culture model using de-epithelialized porcine bladders. GRHL3 expression was detectable in normal human urothelial cells and showed significantly higher mRNA and protein levels in well-differentiated, non-invasive RT4 urothelial carcinoma cells compared to moderately differentiated RT112 cells. GRHL3 expression was absent in anaplastic and invasive T24 cells. Ectopic de novo expression of GRHL3 in T24 cells significantly impaired their migration and invasion properties in vitro and in organ culture. Its downregulation improved the invasive capacity of RT4 cells. The results indicate that GRHL3 may play a role in progression and metastasis in UCB. In addition, this work demonstrates that de-epithelialized porcine bladder organ culture can be a useful, standardized tool to assess the invasive capacity of cancer cells.

Defining the target prior to prostate fusion biopsy: the effect of MRI reporting on cancer detection.

PURPOSE: Definition of targets in multiparametric MRI (mpMRI) prior to MRI/TRUS fusion prostate biopsy either by urologist or radiologist, as a prose report or by illustration is crucial for accurate targeted biopsies (TB). The objective was to analyze the effect of MRI reporting on target definition and cancer detection. METHODS: 202 patients underwent MRI/TRUS fusion biopsy with Artemis™ (Eigen, USA). mpMRI results were submitted in written form to urologists, who marked the targets in the proprietary software. An expert uroradiologist reviewed and marked mpMRI targets blinded to biopsy data. We compared number, localization and volume of targets between the observers and analyzed whether variations impaired TB results by bivariate and logistic regression models. RESULTS: Interobserver variability was moderate regarding number and low regarding localization of targets. Urologists overestimated target volumes significantly compared to radiologists (p = 0.045) and matching target volume between both observers was only 43.9%. Overall cancer detection rate was 69.8 and 52.0% by TB. A higher matching target volume was a significant predictor of cancer in TB (p < 0.001). Logistic regression revealed prostate volume and PI-RADS as independent predictors. Defining targets in incorrect T2w slices in the cranio-caudal axis are one presumable reason for missing cancer in TB. CONCLUSIONS: A high concordance of the target definition between radiologist and urologist is mandatory for accurate TB. Optimized ROI definition is recommended to improve TB results, preferably as contouring in MRI sequences by the radiologist or, if not feasible, by precise MRI reports including specific localization in sequence and slice as well as an illustration. High prostate volume and low PI-RADS score have to be considered as limiting factors for target definition.

Prediction of Locally Advanced Urothelial Carcinoma of the Bladder Using Clinical Parameters before Radical Cystectomy--A Prospective Multicenter Study.

INTRODUCTION: We aimed at developing and validating a pre-cystectomy nomogram for the prediction of locally advanced urothelial carcinoma of the bladder (UCB) using clinicopathological parameters. MATERIALS AND METHODS: Multicenter data from 337 patients who underwent radical cystectomy (RC) for UCB were prospectively collected and eligible for final analysis. Univariate and multivariate logistic regression models were applied to identify significant predictors of locally advanced tumor stage (pT3/4 and/or pN+) at RC. Internal validation was performed by bootstrapping. The decision curve analysis (DCA) was done to evaluate the clinical value. RESULTS: The distribution of tumor stages pT3/4, pN+ and pT3/4 and/or pN+ at RC was 44.2, 27.6 and 50.4%, respectively. Age (odds ratio (OR) 0.980; p < 0.001), advanced clinical tumor stage (cT3 vs. cTa, cTis, cT1; OR 3.367; p < 0.001), presence of hydronephrosis (OR 1.844; p = 0.043) and advanced tumor stage T3 and/or N+ at CT imaging (OR 4.378; p < 0.001) were independent predictors for pT3/4 and/or pN+ tumor stage. The predictive accuracy of our nomogram for pT3/4 and/or pN+ at RC was 77.5%. DCA for predicting pT3/4 and/or pN+ at RC showed a clinical net benefit across all probability thresholds. CONCLUSION: We developed a nomogram for the prediction of locally advanced tumor stage pT3/4 and/or pN+ before RC using established clinicopathological parameters.

Optimizing outcome reporting after radical cystectomy for organ-confined urothelial carcinoma of the bladder using oncological trifecta and pentafecta.

UNLABELLED: Radical cystectomy (RC) for urothelial carcinoma of the bladder (UCB) is associated with heterogeneous functional and oncological outcomes. The aim of this study was to generate trifecta and pentafecta criteria to optimize outcome reporting after RC. METHODS: We interviewed 50 experts to consider a virtual group of patients (age ≤ 75 years, ASA score ≤ 3) undergoing RC for a cT2 UCB and a final histology of ≤pT3pN0M0. A ranking was generated for the three and five criteria with the highest sum score. The criteria were applied to the Prospective Multicenter Radical Cystectomy Series 2011. Multivariable binary logistic regression analyses were used to evaluate the impact of clinical and histopathological parameters on meeting the top selected criteria. RESULTS: The criteria with the highest sum score were negative soft tissue surgical margin, lymph node (LN) dissection of at least 16 LNs, no complications according to Clavien-Dindo grade 3-5 within 90 days after RC, treatment-free time between TUR-BT with detection of muscle-invasive UCB and RC <3 months and the absence of local UCB-recurrence in the pelvis ≤12 months. The first three criteria formed trifecta, and all five criteria pentafecta. A total of 334 patients qualified for final analysis, whereas 35.3 and 29 % met trifecta and pentafecta criteria, respectively. Multivariable analyses showed that the relative probability of meeting trifecta and pentafecta decreases with higher age (3.2 %, p = 0.043 and 3.3 %, p = 0.042) per year, respectively. CONCLUSIONS: Trifecta and pentafecta incorporate essential criteria in terms of outcome reporting and might be considered for the improvement of standardized quality assessment after RC for UCB.

Impact of the use of bowel for urinary diversion on perioperative complications and 90-day mortality in patients aged 75 years or older.

OBJECTIVE: A potential strategy to decrease the high complication rate of radical cystectomy (RC) in the elderly is to avoid the use of bowel for urinary diversion. The aim of this study was to address this issue in a multicentre study of patients aged ≥ 75 years. PATIENTS AND METHODS: We performed a retrospective, multicentre study of a consecutive series of patients aged ≥ 75 years who underwent RC for muscle-invasive bladder cancer between 2006 and 2010. Medical, surgical and wound complications were graded according to the modified Clavien-Dindo classification. RESULTS: A total of 256 patients (68% men, mean age 79.6 years) were analysed. 204 (80%) patients received a urinary diversion with use of bowel and 52 (20%) a ureterocutaneostomy (UC). Patients with UC were older (82.0 vs. 78.9 years, p < 0.001) and had a higher ASA score (2.6 vs. 2.3, p = 0.007), while the mean Charlson score was lower (4.2 vs. 5.6, p < 0.001). Patients with UC had a shorter operating time (279 vs. 311 min, p = 0.002) and a shorter period in the intensive care unit (0.9 vs. 2.2 days). The overall rate of severe complications graded as Clavien III-V was significantly lower in the UC group (11.5%) as compared to patients receiving bowel for urinary diversion (25.0%) (p = 0.003). Severe (Clavien grade III-V) medical (3.9 vs. 10.3%) and surgical (2.1 vs. 14.1%) complications were all less frequent in the UC group. Inpatient, 30- and 90-day mortality was 5.8, 7.7 and 17.3% in the UC group as compared to 3.9, 5.9 and 6.9% in the bowel cohort, respectively. CONCLUSION: UC following RC is associated with a lower complication rate in geriatric patients. The constantly increasing cohort of geriatric, multimorbid patients requiring cystectomy might justify reconsideration of this form of diversion.

Prostate cancer at the peripheral end of prostate biopsy specimen predicts increased risk of positive resection margin after radical prostatectomy: results of a prospective multi-institutional study.

PURPOSE: To test a novel technique of processing prostate biopsy specimen by marking the peripheral end (PE) as a predictive tool for positive resection margin after radical prostatectomy (RP) or for locally advanced carcinoma of the prostate (PC). METHODS: Prospective, multi-institutional study of a consecutive cohort of men who underwent prostate biopsy with marking the peripheral biopsy end and subsequent RP at the same institution. RESULTS: The study cohort comprised 445 men with a mean age of 63 years (40-77 years). Overall, PE-positive cores were found in 174 men (39.1 %) and R1 status was diagnosed in 132 men after RP (29.7 %). In the multivariate analysis, the presence of at least one PE-positive core was correlated with an increased risk of R1 status (OR 2.29, 95 % CI 1.31-4.00, p = 0.003) and was the strongest predictor followed by Gleason score, PSA and percentage of positive cores. Including all predictive parameters, a nomogram with a concordance index of 72.1 % was calculated. In the pT3/pT4 subgroup, PE positivity was the only predictive factor for R1 status (OR 3.03, 95 % CI 1.36-6.75, p = 0.006). In pT2 stage, no single factor was predictive for R1 status. PE-positive biopsies were not predictive for pT3/pT4 stages. CONCLUSIONS: PC at the peripheral end of prostate biopsy specimen predicts an increased risk of R1 status in subsequent RP. This simple and cheap technique may contribute to an increased accuracy of risk stratification for curative treatment for PC.

Perioperative complications and 90-day mortality of radical cystectomy in the elderly (75+): a retrospective, multicentre study.

OBJECTIVE: To assess perioperative complications and 90-day mortality of radical cystectomy (RC) in elderly patients with muscle-invasive bladder cancer (MIBC). MATERIALS AND METHODS: This is a retrospective, multicentre (n = 11) study of a consecutive series of patients ≥75 years who underwent RC for MIBC between 2006 and 2010. Medical, surgical and wound complications were graded according to the modified Clavien-Dindo classification. RESULTS: A total of 256 patients with a mean age of 79.6 years (range 75.0-86.6) were analysed. Urinary diversion with the use of bowel was performed in 79.5% and ureterocutaneostomy in 20.5%, with a higher proportion in the ≥80 cohort (32.2 vs. 14%; p = 0.001). 41.4% of patients had an uneventful postoperative course (Clavien grade 0) and 26.6% developed severe complications (Clavien grade III-V). In a multivariable regression analysis, the Charlson comorbidity index (odds ratio 1.5 per unit increase; p < 0.001) and the body mass index (odds ratio 1.13 per kg/m(2) increase; p = 0.015) were predictors for the development of complications. The 90-day mortality rate was 9% and the independent correlates thereof were the development of severe medical complications (p = 0.004), the American Society of Anesthesiologists (ASA) score (p = 0.03) and age (p = 0.005). CONCLUSIONS: Morbidity and 90-day mortality of RC in the elderly remain substantial. The interrelation between comorbidity, complication rate and 90-day mortality underlines the need for a comprehensive geriatric assessment of elderly patients with MIBC in whom RC is indicated.

The Charlson comorbidity index predicts survival after disease recurrence in patients following radical cystectomy for urothelial carcinoma of the bladder.

OBJECTIVE: To identify prognostic clinical and histopathological parameters, including comorbidity indices at the time of radical cystectomy (RC), for overall survival (OS) after recurrence following RC for urothelial carcinoma of the bladder (UCB). MATERIALS AND METHODS: A retrospective multicenter study was carried out in 555 unselected consecutive patients who underwent RC with pelvic lymph node dissection for UCB from 2000 to 2010. A total of 227 patients with recurrence comprised our study group. Cox proportional hazards regression models were calculated with established variables to assess their independent influence on OS after recurrence. RESULTS: The median time from RC to recurrence and the median OS after recurrence was 10.9 and 5.4 months, respectively. Neither the time to recurrence nor the type of recurrence (systematic vs. local) was predictive of the OS. In contrast, age (hazard ratio (HR) 1.53, p = 0.011), lymph node metastasis (HR 1.56, p = 0.007), and positive surgical margins (HR 1.53, p = 0.046) significantly affected the OS after disease recurrence. In addition, the dichotomized Charlson comorbidity index (CCI; dichotomized into >2 vs. 0-2) was the only comorbidity score with an independent prediction of OS (HR 1.41, p = 0.033). We observed a significant gain in the base model's predictive accuracy, i.e. from 68.4 to 70.3% (p < 0.001), after inclusion of the dichotomized CCI. CONCLUSIONS: We present the first outcome study of comorbidity indices used as predictors of OS after disease recurrence in patients undergoing RC for UCB. The CCI at the time of RC had no significant influence on the time to recurrence but represented an independent predictor of OS after disease recurrence.

Assessing the invasive potential of bladder cancer: development and validation of a new preclinical assay.

PURPOSE: We developed and validated an electrophysiological method for standardized preclinical assessment of the invasive potential of urothelial carcinoma of the bladder. MATERIALS AND METHODS: Human UMUC-3, RT-112, HT-1197 and T24/83 bladder urothelial carcinoma cells, and UROtsa benign urothelial cells were co-cultivated with high resistance MDCK-C7 cells seeded below a 0.4 µm pore membrane of an insert to avoid physical contact and cellular migration. Transepithelial electrical resistance in Ω cm(2) across the MDCK-C7 monolayer was measured longitudinally. Invasive potential coefficients were calculated based on the secretion of proteolytic factors by invading cells. RESULTS: Consistent transepithelial electrical resistance breakdown patterns were reproduced in 14 or more independent samples of each cell line. Coefficients of invasive potential were significantly higher in bladder urothelial carcinoma than UROtsa cells, including a mean ± SD of 1.5 ± 0.32 vs 9.9 ± 4.97 in UMUC-3, 12.5 ± 6.61 in T24/83, 20.5 ± 4.24 in RT-112 and 21.0 ± 5.15 in HT-1197 cells (p <0.001). No correlation was found between the secretion patterns of matrix metalloproteinase-1, 2 and 9, and invasive potential. Stimulation of UROtsa cells with recombinant human epidermal growth factor up-regulated matrix metalloproteinase-9 secretion and significantly increased invasive potential a mean of 1.3 ± 0.22 vs 14.6 ± 3.28 after stimulation with 10 ng/ml epidermal growth factor (p <0.001). CONCLUSIONS: We developed a highly sensitive translational tool to study the initial process of metastatic spread of urothelial carcinoma of the bladder. The presented electrophysiological invasion assay enables reliable quantification of the invasive potential of bladder urothelial carcinoma cells before physical transmigration. It can be used to identify key molecules for bladder urothelial carcinoma invasion and develop new therapeutic strategies.

Do differences in clinical symptoms and referral patterns contribute to the gender gap in bladder cancer?

UNLABELLED: WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: Urothelial carcinoma of the bladder (UCB) is more prevalent in men than women; however, in women the tumour stage is generally more advanced at the time of the diagnosis and the prognosis is worse. Possible explanations include anatomical, genetic and socio-economic factors. The study shows that clinical symptoms before the first-time diagnosis of UCB did not differ between the sexes, while primary care and referral patterns did. Women were more likely to receive symptomatic treatment or therapies for alleged UTIs without further investigation or referral to urological evaluation. The study highlights the fact that there may be a diagnostic delay in women which could contribute to the gender-dependent disparities in stage distribution and prognosis of UCB. OBJECTIVE: To evaluate gender-dependent disparities regarding clinical symptoms, referral patterns or treatments before diagnosis of urothelial carcinoma of the bladder (UCB). PATIENTS AND METHODS: A consecutive series of patients with newly diagnosed UCB completed a questionnaire at the time of admission for elective transurethral resection of a bladder tumour (TURBT). The questionnaire surveyed the presence of haematuria, dysuria, urgency and bladder pain as well as the number of consultations and treatments before urological evaluation. Tumour characteristics, clinical symptoms, treatments and referrals were compared between men and women in the patient series. RESULTS: In men (n = 130) the distribution of tumour stages was pTa 62.3%, pT1 23.1% and pT ≥ 2 12.3%. The respective percentages in women (n = 38) were pTa 57.9%, pT1 23.7% and pT ≥ 2 18.4% (P > 0.05). The prevalence of clinical symptoms in men vs women was as follows: gross haematuria 65 vs 68%, dysuria 32 vs 44%, urgency 61 vs 47%, and nocturia 57 vs 66%, respectively (P > 0.05). A total of 78% of men vs 55% of women directly consulted a urologist (P < 0.05). Symptomatic treatment for voiding disorders/pain was given without further evaluation to 19% of men vs 47% of women 1 year before the diagnosis of UCB (P < 0.05). A total of 3.8% of men vs 15.8% of women received three or more treatments for urinary tract infections (UTIs) within the same time period (P < 0.05). CONCLUSIONS: In the present study there were no gender-related differences in clinical symptoms of UCB, but women were more likely to be treated for voiding complaints or alleged UTIs without further evaluation or referral to urology than men. Gender-dependent disparities in referral patterns exist and might delay definitive diagnosis of UCB in women.

Comparison of radical cystectomy with conservative treatment in geriatric (≥80) patients with muscle-invasive bladder cancer.

INTRODUCTION: The aim of this study was to compare overall survival in elderly patients (≥ 80 years) with muscle-invasive bladder cancer (MIBC) undergoing either radical cystectomy (RC) or conservative treatment. MATERIAL AND METHODS: We performed a retrospective, comparative analysis of overall- and cancer-specific survival in octagenarians with MIBC (≥ pT2) submitted to RC or conservative treatment. Uni- and multivariable Cox regression analysis were performed to assess predictors of overall survival. Cumulative hospital stay was also analyzed for all patients. RESULTS: The RC-group consisted of 33 patients with a mean age of 82.3 years (IQR 80.4-85.4 years) and the bladder preservation a cohort of 35 patients aged 83.8 years (IQR 81.8-88.2 years). No difference was detectable for overall survival (15.9 months versus 9.5 months; p = 0.18) and cancer-specific survival (23.5 months versus 19.5 months p = 0.71) or 90-day mortality (6.1% versus 14.3%; p = 0.43) between the two groups. Patients who received conservative treatment had a shorter cumulative length of hospital stay (p = 0.001). Age at the time of transurethral resection of the bladder (TUR-B) was an independent predictor of the overall survival (p = 0.004). CONCLUSIONS: In this retrospective study, no clear survival benefit was observed for patients ≥80 years submitted either to radical cystectomy or conservative treatment. There was however a trend favoring radical cystectomy but this did not approach statistical significance. Octagenarians that underwent RC however spent more of their remaining lifetime in the hospital than those treated conservatively.

Predictive capacity of four comorbidity indices estimating perioperative mortality after radical cystectomy for urothelial carcinoma of the bladder.

UNLABELLED: What's known on the subject? and What does the study add? The degree of comorbidity significantly affects the course of patients with bladder cancer undergoing radical cystectomy (RC). To our knowledge this is the first study comparing four different comorbidity indices in patients undergoing RC for urothelial carcinoma to assess the best clinical predictors for 90-day perioperative mortality. We concluded that the ASA score should be the method of choice, as it showed a predictive ability superior to that of ECOG and CCI, and is much easier to generate than the ACE-27. OBJECTIVE: To evaluate which of the following among the Adult Comorbidity Evaluation-27 (ACE-27), the Charlson Comorbidity Index (CCI), the Eastern Cooperative Oncology Group performance status (ECOG) and the American Society of Anesthesiologists (ASA) comorbidity scores correlate best with perioperative mortality after radical cystectomy (RC) for urothelial carcinoma (UC) of the bladder. PATIENTS AND METHODS: A study was carried out on 555 unselected consecutive patients without neoadjuvant chemotherapy who underwent RC for UC of the bladder from 2000 to 2010 at one of two institutions. Patients' medical records were reviewed retrospectively. We established a defined binary linear progression model based on clinical variables to predict perioperative mortality <90 days after RC (90PM). To this model we added, individually, the comorbidity indices ACE-27, CCI, ECOG, and ASA to assess their predictive capacity regarding 90PM. RESULTS: The overall 90PM was 7.9%. Age (P = 0.01) and clinical distant metastatic tumour stage (P = 0.002) were independent predictors for 90PM in the multivariate analysis. Each of the four investigated comorbidity indices was able to significantly increase the predictive capacity of the basic model: ECOG +13.5%, (odds ratio [OR]: 1.61, P = 0.036; area under the curve [AUC] 74.7), ASA Score +28.3% (OR: 2.19, P = 0.004; AUC 76.1), Charlson Index +12.3% (OR: 1.31, P = 0.047; AUC 73.8) and ACE-27 + 29.8% (OR: 1.72, P = 0.004; AUC 76.1). CONCLUSIONS: ASA and ACE-27 show a nearly identical clinical predictive value for perioperative mortality. Both scores could be considered for clinical practice. With regard to ease of generation and availability, the ASA score can be regarded as the best instrument.

Accurate risk assessment of patients with asymptomatic hematuria for the presence of bladder cancer.

PURPOSE: Bladder cancer is frequently diagnosed during a workup for hematuria. However, most patients with microscopic hematuria and many with gross hematuria are not appropriately referred to urologists. We hypothesized that in patients presenting with asymptomatic hematuria the risk of having bladder cancer can be predicted with high accuracy. Toward this end, we analyzed risk factors in patients with asymptomatic hematuria and developed a nomogram for the prediction of bladder cancer presence. METHODS: Data from 1,182 consecutive subjects without a history of bladder cancer undergoing initial evaluation for asymptomatic hematuria were collected at three centers. Clinical risk factors including age, gender, smoking status, and degree of hematuria were recorded. All subjects underwent standard workup including voided cytology, upper tract imaging, and cystourethroscopy. Factors associated with the presence of bladder cancer were evaluated by univariable and multivariable logistic regression analyses. The multivariable analysis was used to construct a nomogram. Internal validation was performed using 200 bootstrap samples. RESULTS: Of the 1,182 subjects who presented with asymptomatic hematuria, 245 (20.7 %) had bladder cancer. Increasing age (OR = 1.03, p < 0.0001), smoking history (OR = 3.72, p < 0.0001), gross hematuria (OR = 1.71, p = 0.002), and positive cytology (OR = 14.71, p < 0.0001) were independent predictors of bladder cancer presence. The multivariable model achieved 83.1 % accuracy for predicting the presence of bladder cancer. CONCLUSIONS: Bladder cancer presence can be predicted with high accuracy in patients who present with asymptomatic hematuria. We developed a nomogram to help optimize referral patterns (i.e., timing and prioritization) of patients with asymptomatic hematuria.

A comparison of hexaminolevulinate (Hexvix(®)) fluorescence cystoscopy and white-light cystoscopy for detection of bladder cancer: results of the HeRo observational study.

BACKGROUND: To date, no study has presented results of photodynamic diagnosis (PDD) cystoscopy compared with white-light cystoscopy (WLC) in daily practice. The aim of the present study is to evaluate the diagnostic accuracy of hexylaminolevulinate hydrochloride (Hexvix(®)) PDD cystoscopy compared with standard WLC used in daily practice. METHODS: An observational, open-label, comparative, controlled (within patient), multicenter study was carried out on 96 consecutive patients with suspected or confirmed bladder cancer. All patients had standard WLC followed by blue-light cystoscopy (BLC). Positive lesions detected using WLC and BLC were recorded. Biopsies/resection of each positive lesion were taken after the bladder was inspected. Sensitivity, specificity, positive predictive value, and negative predictive value with each method were calculated. RESULTS: Overall, 234 suspicious lesions were detected; 108 (46.2%) were histologically confirmed to be bladder tumors/carcinoma in situ (CIS). The sensitivity of BLC biopsies was significantly higher than for WLC technique (99.1 vs 76.8%; p < 0.00001). The relative sensitivity of BLC versus WLC was 1.289, showing superiority of BLC of 28.9%. The specificity of BLC biopsies was not significantly different compared with WLC (36.5 vs 30.2%). Positive predictive value for BLC- and WLC-guided biopsies was 54.9 and 50.9%, respectively. Negative predictive value per biopsy for BLC- and WLC-guided biopsies was 97.4 and 64.8%, respectively. BLC and WLC reached the correct diagnosis in 97.9 and 88.5% of patients, respectively. This difference was statistically significant (p = 0.0265). The lack of a random biopsy protocol was the major limitation of the study. CONCLUSIONS: Hexvix(®) PDD cystoscopy used in daily practice enhances the diagnostic accuracy of standard cystoscopy with higher negative predictive value, potentially permitting an improvement in patient prognosis.

Different patients, different preferences: A multicenter assessment of patients' personality traits and anxiety in shared decision making.

OBJECTIVE: Patient-centered care and shared decision making (SDM) are generally recognized as the gold standard for medical consultations, especially for preference-sensitive decisions. However, little is known about psychological patient characteristics that influence patient-reported preferences. We set out to explore the role of personality and anxiety for a preference-sensitive decision in bladder cancer patients (choice of urinary diversion, UD) and to determine if anxiety predicts patients' participation preferences. METHODS: We recruited a sample of bladder cancer patients (N = 180, primarily male, retired) who awaited a medical consultation on radical cystectomy and their choice of UD. We asked patients to fill in a set of self-report questionnaires before this consultation, including measures of treatment preference, personality (BFI-10), anxiety (STAI), and participation preference (API and API-Uro), as well as sociodemographic characteristics. RESULTS: Most patients (79%) indicated a clear preference for one of the treatment options (44% continent UD, 34% incontinent UD). Patients who reported more conscientiousness were more likely to prefer more complex methods (continent UD). The majority (62%) preferred to delegate decision making to healthcare professionals. A substantial number of patients reported elevated anxiety (32%), and more anxiety was predictive of higher participation preference, specifically for uro-oncological decisions (ß = 0.207, p < 0.01). CONCLUSIONS: Our findings provide insight into the role of psychological patient characteristics for SDM. Aspects of personality such as conscientiousness influence treatment preferences. Anxiety contributes to patients' motivation to be involved in pertinent decisions. Thus, personality and negative affect should be considered to improve SDM.

Impact of sacral neuromodulation on female sexual function and his correlation with clinical outcome and quality of life indexes: a monocentric experience.

INTRODUCTION: Lower urinary tract symptoms (LUTS) have a profound impact on physical, social, and sexual well-being. Sacral neuromodulation (SNM) may have a positive effect on sexuality, though few studies have so far evaluated its impact on female sexual function. AIM: To prospectively assess changes in sexual function, clinical outcome and quality of life after SNM in female patients with overactive bladder (OAB) and their possible correlation with improvement in urinary symptoms and quality of life indexes. MAIN OUTCOME MEASURES: Correlations between differences in Female Sexual Function Index (FSFI) scores and in clinical outcome and correlations between differences in FSFI, SF36, and IQoL scores were evaluated by Spearman's coefficient. Comparison between preoperative, midterm follow-up (MFU), and last follow-up (FFU) visits were performed by generalized linear model (GLM) for repeated measurements. METHODS: Between May 2003 and December 2008, 30 consecutive female patients (median age 53 years, range 35-79) with OAB underwent the two-stage procedure of SNM. Only 16 (53%) patients were considered eligible; these completed a bladder diary, the FSFI, the Status of Health questionnaire (SF36) and the Incontinence Quality of Life Index (IQoL) before implantation and on follow-up examinations. RESULTS: The results were analyzed before implantation, on MFU (median MFU 22.5 months) and on FFU (median FFU period 36.3 months). Regarding sexuality, the mean improvement in the total FSFI score was 27.9% on MFU and 29.3% on FFU. Only four patients (25%) showed a >50% improvement in global FSFI score on MFU, and 3 (25%) on FFU. A significant correlation was found between clinical improvement and improvement in sexual function. No significant correlation was found between differences in FSFI and quality of life indexes (IQoL and SF36). CONCLUSION: Our results demonstrate that improvement in the quality of sexual function in female patients with OAB correlates with improvement in urinary symptoms.

POFUT1 mRNA expression as an independent prognostic parameter in muscle-invasive bladder cancer.

Muscle-invasive bladder cancer (MIBC) is characterized by high recurrence and rapid progression. Progression is linked to changes in glycan structures and altered levels of glycosyltransferases. The relationship of mRNA expression by glycosyltransferase genes B4GALT1, EXT1, MGAT5B, and POFUT1 to the probability of surviving MIBC after radical cystectomy has not yet been investigated. mRNA expression was analyzed using qRT-PCR in formalin-fixed and paraffin-embedded tumor samples (n = 105; 74% male patients and 26% female patients; median age = 72 years), correlated with histopathological variables, and evaluated by means of multivariable Cox regression analysis regarding to overall survival (OS), cancer-specific survival (CSS), and disease-free survival (DFS). Multivariable Cox regression analysis identified POFUT1 mRNA expression as superior prognostic marker, compared with currently used histological tumor stage methods, for CSS by MIBC patients following radical cystectomy. Thus, the patients with low POFUT1 mRNA were at a 4.9-fold greater risk for cancer-specific death according to the multivariable analysis (p = 0.0001). Low mRNA levels predicted poor survival according to the Kaplan-Meier analysis ((POFUT1:OS p = 0.0014; CSS p = 0.0007; DFS p = 0.0088); (EXT1:OS p = 0.0150; CSS p = 0.0130; DFS p = 0.0286); (B4GALT1:CSS p = 0.0134; DFS p = 0.0493)). A subgroup analysis of patients without lymph node metastasis (pN-; n = 73) indicated that low expression of POFUT1 predicted reduced OS (p = 0.0073), CSS (p = 0.0058,) and DSS (p = 0.0079). Low levels of POFUT1 mRNA are an independent prognostic indicator for OS and CSS in MIBC patients following radical cystectomy. This finding demonstrates the importance of altered glycosylation for the progress of MIBC.

[The impact of radical cystectomy on health-related quality of life and potential for optimisation]. / Einfluss der radikalen Zystektomie auf die Lebensqualität und Strategien für deren Erhalt.

Radical cystectomy may have a major impact on the lives of affected patients. Older patients often have a reduced life expectancy after radical cystectomy. Therefore, aspects of health-related quality of life (HRQOL) have to be balanced against a solely tumour-directed therapy. In this narrative review, factors influencing the HRQOL of affected patients were identified and discussed by selective literature search.Besides strategies to minimise perioperative morbidity, these include a patient-oriented and individualised treatment plan taking into account factors such as age, comorbidities, choice of urinary diversion and age-specific conditions, in particular frailty. Patient-reported outcome measures (PROMs) are crucial instruments to assess HRQOL outcomes and should be further implemented into routine clinical use.

Correction: Excess hepsin proteolytic activity limits oncogenic signaling and induces ER stress and autophagy in prostate cancer cells.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Novel electromagnetic lithotriptor for upper tract stones with and without a ureteral stent.

PURPOSE: We compared the treatment efficacy and safety of the novel Lithoskop electromagnetic extracorporeal shock wave lithotriptor for upper urinary tract stones with and without prior ureteral stent placement. MATERIALS AND METHODS: A total of 665 consecutive patients harboring single renal or ureteral stones underwent shock wave lithotripsy between August 2006 and July 2008. In 75 and 46 patients with renal and ureteral stones, respectively, stents were placed before the first shock wave lithotripsy session. Treatment outcome was assessed in relation to stent placement. All data were derived from a prospectively maintained database. RESULTS: The mean size of nonstented vs stented renal and ureteral stones was 8.6 vs 12.5 mm (p <0.0001) and 7.1 vs 7.3 mm (p = 0.6), respectively. The stone-free rate in nonstented vs stented renal and ureteral stone cases was 76.3% vs 77.3% and 91.4% vs 93.5%, respectively (each p >0.99). The total energy applied per stone was 110 +/- 83 vs 150 +/- 89 J (p <0.0001) and 183 +/- 131 vs 209 +/- 125 J (p = 0.1), respectively. Auxiliary measures were required after shock wave lithotripsy for renal and ureteral stones in 5.4% and 10.8% of nonstented, and in 1.3% and 4.3% of stented cases, respectively. No complications were detected in stented renal and ureteral stone cases compared to 2.9% and 6.9% in nonstented cases, respectively. CONCLUSIONS: A high success rate and a low complication rate were achieved in renal and ureteral stone cases with and without prior ureteral stent placement. Total energy needed to achieve a stone-free state did not differ between stented and nonstented ureteral cases, suggesting the absence of a significant influence of the stent. Overall stents decreased complications necessitating hospitalization and auxiliary invasive measures.