Assessment of different continence definitions in the context of the randomized multicenter prospective LAP-01 trial-Does the best definition change over time?

BACKGROUND: A uniform definition of continence is urgently needed to allow the comparison of study results and to estimate patient outcomes after radical prostatectomy (RP). To identify a practical definition that includes both objective and subjective aspects in a tangible way, we assessed different continence definitions and evaluated which best reflects the patients' subjective perception of continence. METHODS: Our analyses included 718 patients that underwent either robot-assisted radical prostatectomy (RARP) or laparoscopic radical prostatectomy (LRP) in a multicenter randomized patient-blinded trial. Continence was assessed through patient questionnaires prior to and at 3, 6 and 12 months after surgery which included the number of pads used per day, the ICIQ-SF and the question "Do you suffer from incontinence? (yes/no)" to assess subjective continence. We used Krippendorff's Alpha to calculate the agreement of different continence definitions with the subjective perception. RESULTS: At 3 months, the "0/safety pad" definition shows the highest agreement by alpha = 0.70 (vs. 0.63 for "0 pads" and 0.37 for "0-1 pad"). At 6 and 12 months "0 pads" is the better match, with alpha values of 0.69 (vs. 0.62 and 0.31) after 6 months and 0.70 (vs. 0.65 and 0.32) after 12 months. The ICIQ-SF score shows good correlation with the subjective continence at 3 months (alpha = - 0.79), the coefficient then decreasing to - 0.69 and - 0.59 at 6 and 12 months. CONCLUSION: The best continence definition according to the patients' perspective changes over time, "0 pads" being the superior criterion in the long-term. We recommend using the 0-pad definition for standardized continence reporting, as it is simple yet as accurate as possible given the inevitably high subjectivity of continence perception. Trial registration The LAP-01 trial was registered with the U.S. National Library of Medicine clinical trial registry (clinicaltrials.gov), NCT number: NCT03682146, and with the German Clinical Trial registry (Deutsches Register Klinischer Studien), DRKS ID number: DRKS00007138.

Quality of life after robotic-assisted and laparoscopic radical prostatectomy: Results of a multicenter randomized controlled trial (LAP-01).

BACKGROUND: To explore cross-sectional and longitudinal differences in general health-related and prostate cancer-specific quality of life (QoL) after robotic-assisted (RARP) and laparoscopic (LRP) radical prostatectomy and to analyze predictive variables for QoL outcomes. METHODS: In this multicenter, randomized controlled trial, prostate cancer patients were randomly assigned 3:1 to undergo either RARP or LRP. Patient-reported outcomes were prospectively collected before and 1, 3, 6, 12 months after radical prostatectomy and included QoL as a secondary outcome. Validated questionnaires were used to assess general health-related (EORTC QLQ-C30) and prostate cancer-specific (QLQ-PR25) QoL. Cross-sectional and longitudinal contrasts were analyzed through linear mixed models. Predictive variables for QoL outcomes were identified by general linear modeling. RESULTS: Of 782 randomized patients, QoL was evaluable in 681 patients. In terms of general QoL, the cross-sectional analysis showed only small differences between study arms, whereas longitudinal comparison indicated an advantage of RARP on recovery: RARP patients reported an earlier return to baseline in global health status (3 vs. 6 months) and social functioning (6 vs. 12 months). In role functioning, only the RARP arm regained baseline scores. Regarding prostate-specific QoL, LRP patients experienced more urinary symptoms and reported 3.2 points (95% confidence interval 0.4-6, p = 0.024) higher mean scores at 1-month follow-up and in mean 2.9 points (0.1-5, p = 0.042) higher urinary symptoms scores at 3-month follow-up than RARP patients. There were no other significant differences between treatment groups. Urinary symptoms, sexual activity, and sexual function remained significantly worse compared with baseline at all time points in both arms. CONCLUSIONS: Compared with LRP, the robotic approach led to an earlier return to baseline in several domains of general health-related QoL and better short-term recovery of urinary symptoms. Predictive variables such as the scale-specific baseline status and bilateral nerve-sparing were confirmed.

Age-stratified outcomes after radical prostatectomy in a randomized setting (LAP-01): do younger patients have more to lose?

OBJECTIVE: Age is known to have an impact on outcomes after radical prostatectomy (RP). However, age differences can be investigated from a cross-sectional as well as from a longitudinal perspective. This study combines both perspectives. MATERIALS AND METHODS: LAP-01 is the first multicenter randomized patient blinded trial comparing outcomes after robotic-assisted and laparoscopic RP. This study stratified the entire population that received nerve-sparing surgery and was potent at baseline by the following ages: ≤ 60 years, 61-65 years, and > 65 years. Potency was assessed using the IIEF-5. The EORTC QLQ-C30 was used for global health perception and the EORTC QLQ-PR25 for urinary symptoms. Continence was assessed by the number of pads used. Longitudinal change was assessed using either validated anchor-based criteria or the 1 or 0.5-standard-deviation criterion. Worsening of continence was measured by increasing numbers of pads. RESULTS: 310 patients were included into this study. Older patients had a significantly higher risk for worsening of continence at 3 and 6 months (OR 2.21, 95% CI [1.22, 4.02], p = 0.009 and OR 2.00, 95% CI [1.16, 3.46], p = 0.013, respectively); at 12 months, the odds of worsening did not differ significantly between age groups. Potency scores were better in younger patients from a cross-sectional perspective, but longitudinal change did not differ between the age groups. In contrast, global health perception was better in older patients from a cross-sectional perspective and longitudinal decreases were significantly more common among the youngest patients, at 12 months (36.9% vs. 24.4%, p = 0.038). CONCLUSION: From a cross-sectional perspective, function scores were better in younger patients, but from a longitudinal perspective, age differences were found in continence only. In contrast, global health scores were better in older patients from a cross-sectional and longitudinal perspective. TRIAL REGISTRATION: The LAP-01 trial was registered with the U.S. National Library of Medicine clinical trial registry (clinicaltrials.gov), NCT number: NCT03682146, and with the German Clinical Trial registry (Deutsches Register Klinischer Studien), DRKS ID number: DRKS00007138.

Robotic-assisted Versus Laparoscopic Radical Prostatectomy: 12-month Outcomes of the Multicentre Randomised Controlled LAP-01 Trial.

BACKGROUND: Recently, our LAP-01 trial demonstrated superiority of robotic-assisted laparoscopic radical prostatectomy (RARP) over conventional laparoscopic radical prostatectomy (LRP) with respect to continence at 3 mo. OBJECTIVE: To compare the continence, potency, and oncological outcomes between RARP and LRP in the 12-mo follow-up. DESIGN, SETTING, AND PARTICIPANTS: In this multicentre, randomised, patient-blinded controlled trial, patients referred for radical prostatectomy to four hospitals in Germany were randomly assigned (3:1) to undergo either RARP or LRP. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Continence was assessed as a patient-reported outcome through validated questionnaires. Secondary endpoints included potency and oncological outcomes. Data were statistically analysed by bivariate tests and multivariable models. RESULTS AND LIMITATIONS: At 12 mo, follow-up data were available for 701 of 782 patients. Continence at 6 and 12 mo after surgery was better in RARP patients, however no longer statistically significant (p = 0.068 and 0.38, respectively). Patients who were potent at baseline and underwent nerve-sparing surgery reported significantly higher potency after RARP, as defined by the capability to maintain an erection sufficient for intercourse at 3 (p = 0.005), 6 (p = 0.018), and 12 mo (p = 0.013). There were no statistically significant differences in oncological outcomes at 12 mo. It is a limitation that the influence of different anastomotic techniques was not investigated in this study. CONCLUSIONS: Both LRP and RARP offer a high standard of therapy for prostate cancer patients. However, robotic assistance offers better functional outcomes in specific areas such as potency and early continence in patients who are eligible for nerve-sparing RP. PATIENT SUMMARY: We compared outcomes 12 mo after radical prostatectomy between robotic-assisted and conventional laparoscopy. Both methods were equivalent with respect to oncological outcomes. Better recovery of continence in patients with robotic-assisted surgery, which was observed at 3 mo, blurred up to 12 mo. A benefit of robotic-assisted surgery was also observed in potency.

Robotic-assisted Versus Laparoscopic Surgery: Outcomes from the First Multicentre, Randomised, Patient-blinded Controlled Trial in Radical Prostatectomy (LAP-01).

BACKGROUND: The LAP-01 trial was designed to address the lack of high-quality literature comparing robotic-assisted (RARP) and laparoscopic (LRP) radical prostatectomy. OBJECTIVE: To compare the functional and oncological outcomes between RARP and LRP at 3 mo of follow-up. DESIGN, SETTING, AND PARTICIPANTS: In this multicentre, randomised, patient-blinded controlled trial, patients referred for radical prostatectomy to four hospitals in Germany were randomly assigned (3:1) to undergo either RARP or LRP. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was time to continence recovery at 3 mo based on the patient's pad diary. Secondary outcomes included continence and potency as well as quality of life in addition to oncological outcomes for up to 3 yr of follow-up. Time to continence was analysed by log-rank test and depicted by the Kaplan-Meier method. Continuous measurements were analysed by means of linear mixed models. RESULTS AND LIMITATIONS: A total of 782 patients were randomised. The primary endpoint was evaluable in 718 patients (547 RARPs; full analysis set). At 3 mo, the difference in continence rates was 8.7% in favour of RARP (54% vs 46%, p = 0.027). RARP remained superior to LRP even after adjustment for the randomisation stratum nerve sparing and age >65 yr (hazard ratio = 1.40 [1.09-1.81], p = 0.008). A significant benefit in early potency recovery was also identified, while similar oncological and morbidity outcomes were documented. It is a limitation that the influence of different anastomotic techniques was not investigated in this study. CONCLUSIONS: RARP resulted in significantly better continence recovery at 3 mo. PATIENT SUMMARY: In this randomised trial, we looked at the outcomes following radical prostate surgery in a large German population. We conclude that patients undergoing robotic prostatectomy had better continence than those undergoing laparoscopic surgery when assessed at 3 mo following surgery. Age and the nerve-sparing technique further affected continence restoration.

To defer or not to defer? A German longitudinal multicentric assessment of clinical practice in urology during the COVID-19 pandemic.

INTRODUCTION: After the outbreak of COVID-19 unprecedented changes in the healthcare systems worldwide were necessary resulting in a reduction of urological capacities with postponements of consultations and surgeries. MATERIAL AND METHODS: An email was sent to 66 urological hospitals with focus on robotic surgery (RS) including a link to a questionnaire (e.g. bed/staff capacity, surgical caseload, protection measures during RS) that covered three time points: a representative baseline week prior to COVID-19, the week of March 16th-22nd and April 20th-26th 2020. The results were evaluated using descriptive analyses. RESULTS: 27 out of 66 questionnaires were analyzed (response rate: 41%). We found a decrease of 11% in hospital beds and 25% in OR capacity with equal reductions for endourological, open and robotic procedures. Primary surgical treatment of urolithiasis and benign prostate syndrome (BPS) but also of testicular and penile cancer dropped by at least 50% while the decrease of surgeries for prostate, renal and urothelial cancer (TUR-B and cystectomies) ranged from 15 to 37%. The use of personal protection equipment (PPE), screening of staff and patients and protection during RS was unevenly distributed in the different centers-however, the number of COVID-19 patients and urologists did not reach double digits. CONCLUSION: The German urological landscape has changed since the outbreak of COVID-19 with a significant shift of high priority surgeries but also continuation of elective surgical treatments. While screening and staff protection is employed heterogeneously, the number of infected German urologists stays low.

Comparison of various continence definitions in a large group of patients undergoing radical prostatectomy: a multicentre, prospective study.

BACKGROUND: Due to the usage of various measurement methods and definitions, comparing continence rates after radical prostatectomy is a challenging task. This study compares continence rates based on different methods and aims to identify the definition for continence which agrees best with the patients' subjective assessment of continence. Additionally, continence was controlled for multiple influencing factors. METHODS: This prospective multicentre study was carried out in seven hospitals throughout Germany. Before and at 3, 6, and 12 months after surgery self-reporting questionnaires were completed and returned by 329 (84.4%) of 390 eligible patients. The questionnaires were independently evaluated and analysed by a third party. Association of continence with demographic, operative, and tumour factors in an ongoing comprehensive prostate cancer database was evaluated. RESULTS: The continence rate drops substantially for patients undergoing radical prostatectomy but increases again with time. Concrete numbers vary considerably depending on definition - 44% at 3 months and 68% at 12 months after surgery (0 pads) vs. 71 and 90% (0-1 pads). Significant confounding variables regarding continence rate are nerve-sparing procedure, categorized Gleason score, rehabilitative cure treatment, and pelvic floor training. The definition of 0 pads for continence coincides greater than 0-1 pads with the patients' self-assessment of being continent. CONCLUSION: A standardized definition for continence would be desirable, as it is one of the most important preconditions to guarantee sound comparison of continence rates. Since there are enough other factors that make comparison difficult, we suggest using the definition of "0 pads". It is easily measured objectively, leaves no room for interpretation, and agrees best with the patients' self-assessment.

Urinary bladder cancer risk factors in an area of former coal, iron, and steel industries in Germany.

This study was performed to investigate the frequency of bladder cancer in patients with an occupational history such as underground hard coal mining and/or painting after the structural change in the local industry. A total of 206 patients with bladder cancer and 207 controls were enlisted regarding occupational and nonoccupational bladder cancer risk factors by questionnaire. The phase II enzymes N-acetyltransferase 2 (NAT2), glutathione S-transferases M1 (GSTM1), and T1 (GSTT1) and the single nucleotide polymorphism (SNP) rs11892031[A/C] reported to be associated with bladder cancer in genome-wide association studies were genotyped. The bladder cancer risk in varnishers and underground hard coal miners was increased as previously shown in a study in this area performed in the 1980s. The occupation of a car mechanic was associated with a significantly elevated bladder cancer risk and higher in the case of underground hard coal miners even though the mine was closed in 1987. The frequency of GSTM1 negative genotype was comparable in cases and controls (53% versus 54%). In the case of NAT2, the slow NAT2 genotype was more frequent (62% versus 58%) and ultra-slow NAT2 genotype (NAT2*6A and/or *7B alleles only) was 23% versus 15%. An occupational history of a varnisher or an underground hard coal miner remains a risk factor for bladder cancer occurrence. Data indicate that in the case of bladder cancer, GSTM1 is a susceptibility factor related to environmental and/or occupational exposure.

Micro-brushing-based technique to gain fresh urothelial cells for gene expression analysis.

The gold standard of saving fresh tissue in liquid nitrogen has some serious disadvantages in that this process is not available in daily medical routine practices even in many tumor centers. Our approach of a new minimally invasive technique is obtaining urothelial cells via micro-brushing the urinary bladder on the occasion of urological routine methods such as transurethral resection (TUR). Urothelial cells were obtained from 25 patients via two different micro-brushes from tumor tissue and from macroscopically healthy tissue during TUR. These cells were immediately transferred into RNA stabilization reagent and stored at -20°C. Later, mRNA was isolated, transcribed into cDNA, and amplified. cDNA was stored at -20°C until analysis. The mean RNA quantity was 99.5 ng/µl from tumor tissues and 66.3 ng/µl from macroscopically tumor-free tissue, enabling a considerable number of analyses. The quality of the gained cDNA allowed semi-quantitative PCR analysis of GSTM1 expression as well as quantitative PCR analysis of c-Myc expression. The new technique presents several important advantages. First, staging and grading of the stained tumor sample can be examined immediately, whereas fresh frozen sample is not examined until some days later. Further, this method can be applied in hospitals with no access to liquid nitrogen or without capability to provide an additional examination of frozen tumor sample by a pathologist. This presented minimally invasive method enables investigation of gene expression in the urinary bladder without disadvantages of the need for storage of fresh tissues in liquid nitrogen.

Cancer-related fatigue in patients before and after radical prostatectomy. Results of a prospective multi-centre study.

PURPOSE: A multi-centre, longitudinal study was conducted to assess the prevalence of fatigue amongst men with localized prostate cancer, to describe several dimensions of fatigue and to explore the predictability of fatigue by psychological distress and physical function. METHODS: The prevalence of fatigue was evaluated using the Multidimensional Fatigue Inventory in 329 prostate cancer patients before, 3, 6 and 12 months after surgery. Psychological distress was assessed using the Hospital Anxiety and Depression Scale. Physical function was measured using the EORTC QLQ-C30. RESULTS: After surgery, about 14 % of the patients were screened with chronic fatigue. For all dimensions of fatigue, only small longitudinal changes could be observed. Psychological distress could be identified as a good predictor of fatigue after but not before surgery. CONCLUSIONS: Radical prostatectomy has no or little impact on the prevalence of fatigue. However, about 14 % of patients with chronic fatigue could possibly benefit from psychosomatic interventions. Interventions should consider the simultaneous appearance of fatigue and psychological distress and a reduced physical function.

Rs11892031[A] on chromosome 2q37 in an intronic region of the UGT1A locus is associated with urinary bladder cancer risk.

Recently, rs11892031[A] has been identified in a genome-wide association study (GWAS) to confer increased risk of urinary bladder cancer (UBC). To confirm this association and additionally study a possible relevance of exposure to urinary bladder carcinogens, we investigated the IfADo UBC study group, consisting of eight case-control series from different regions including 1,805 cases and 2,141 controls. This analysis was supplemented by a meta-analysis of all published data, including 13,395 cases and 54,876 controls. Rs11892031 A/A was significantly associated with UBC risk in the IfADo case-control series adjusted to cigarette smoking, gender, age and ethnicity (OR = 1.18; 95% CI = 1.02-1.37; P = 0.026). In the meta-analysis, a convincing association with UBC risk was obtained (OR = 1.19; 95% Cl = 1.12-1.26; P < 0.0001). Interestingly, the highest odds ratios were obtained for individual case-control series with a high degree of occupational exposure to polycyclic aromatic hydrocarbons and aromatic amines: cases with suspected occupational UBC (OR = 1.41) and cases from the highly industrialized Ruhr area (OR = 1.98) compared with Ruhr area controls (all combined OR = 1.46). Odds ratios were lower for study groups with no or a lower degree of occupational exposure to bladder carcinogens, such as the Hungary (OR = 1.02) or the ongoing West German case-control series (OR = 1.06). However, the possible association of rs11892031[A] with exposure to bladder carcinogens still should be interpreted with caution, because in contrast to the differences between the individual study groups, interview-based data on occupational exposure were not significantly associated with rs11892031. In conclusion, the association of rs11892031[A] with UBC risk could be confirmed in independent study groups.

Urinary bladder cancer risk in relation to a single nucleotide polymorphism (rs2854744) in the insulin-like growth factor-binding protein-3 (IGFBP3) gene.

Currently, twelve validated genetic variants have been identified that are associated with urinary bladder cancer (UBC) risk. However, those validated variants explain only 5-10% of the overall inherited risk. In addition, there are more than 100 published polymorphisms still awaiting validation or disproval. A particularly promising of the latter unconfirmed polymorphisms is rs2854744 that recently has been published to be associated with UBC risk. The [A] allele of rs2854744 has been reported to be associated with a higher promoter activity of the insulin-like growth factor-binding protein-3 (IGFBP3) gene, which may lead to increased IGFBP-3 plasma levels and cancer risk. Therefore, we investigated the association of rs2854744 with UBC in the IfADo case-control series consisting of 1,450 cases and 1,725 controls from Germany, Hungary, Venezuela and Pakistan. No significant association of rs2854744 with UBC risk was obtained (all study groups combined: unadjusted P = 0.4446; adjusted for age, gender and smoking habits P = 0.6510), besides a small effect of the [A] allele in the Pakistani study group opposed to the original findings (unadjusted P = 0.0508, odds ratio (OR) = 1.43 for the multiplicative model) that diminished after adjustment for age, gender and smoking habits (P = 0.7871; OR = 0.93). Associations of rs2854744 with occupational exposure to urinary bladder carcinogens and smoking habits were also not present. A meta-analysis of all available case-control series including the original discovery study resulted in an OR of 1.00 (P = 0.9562). In conclusion, we could not confirm the recently published hypothesis that rs2854744 in the IGFBP3 gene is associated with UBC risk.

Early continence in patients with localized prostate cancer. A comparison between open retropubic (RRPE) and endoscopic extraperitoneal radical prostatectomy (EERPE).

OBJECTIVE: The study examined and compared continence rates in prostate cancer patients who had undergone either open retropubic prostatectomy (RRPE) or endoscopic extraperitoneal radical prostatectomy (EERPE). The core question was whether the surgical approach had an effect on the patients' continence status 3 months after surgery. METHODS: We conducted a multicentric, longitudinal study in 7 German hospitals. Three hundred fifty prostate cancer patients (166 EERPE, 184 RRPE) were asked to self-assess symptoms associated with urinary incontinence (UI) 1 day before and 3 months after prostatectomy. Symptoms of UI were assessed using the EORTC QLQ-PR25 questionnaire. Urinary continence was defined according to (1) the use of no protective pad, (2) the use of up to a single protective pad in a 24-hour period, and (3) according to the patient's self-assessment. A binary regression model was employed to predict early continence status. RESULTS: Three months after prostatectomy, 44% of patients who underwent EERPE and 40% of patients who underwent RRPE were completely continent. Patients who underwent nerve-sparing prostatectomy and patients younger than 65 years had a better chance of regaining urinary continence earlier. The surgical approach had no significant impact on the patients' continence status. Limitations of the study are a drop-out rate of 39% and sociodemographic and clinical differences between both treatment groups. CONCLUSIONS: Three months after prostatectomy, there were no significant differences between both treatment groups regarding urinary continence. The surgical approach had no significant effect on the patients' continence status. Higher age and non-nerve-sparing surgery are associated with a longer period of convalescence.

Genotyping NAT2 with only two SNPs (rs1041983 and rs1801280) outperforms the tagging SNP rs1495741 and is equivalent to the conventional 7-SNP NAT2 genotype.

Genotyping N-acetyltransferase 2 (NAT2) is of high relevance for individualized dosing of antituberculosis drugs and bladder cancer epidemiology. In this study we compared a recently published tagging single nucleotide polymorphism (SNP) (rs1495741) to the conventional 7-SNP genotype (G191A, C282T, T341C, C481T, G590A, A803G and G857A haplotype pairs) and systematically analysed if novel SNP combinations outperform the latter. For this purpose, we studied 3177 individuals by PCR and phenotyped 344 individuals by the caffeine test. Although the tagSNP and the 7-SNP genotype showed a high degree of correlation (R=0.933, P<0.0001) the 7-SNP genotype nevertheless outperformed the tagging SNP with respect to specificity (1.0 vs. 0.9444, P=0.0065). Considering all possible SNP combinations in a receiver operating characteristic analysis we identified a 2-SNP genotype (C282T, T341C) that outperformed the tagging SNP and was equivalent to the 7-SNP genotype. The 2-SNP genotype predicted the correct phenotype with a sensitivity of 0.8643 and a specificity of 1.0. In addition, it predicted the 7-SNP genotype with sensitivity and specificity of 0.9993 and 0.9880, respectively. The prediction of the NAT2 genotype by the 2-SNP genotype performed similar in populations of Caucasian, Venezuelan and Pakistani background. A 2-SNP genotype predicts NAT2 phenotypes with similar sensitivity and specificity as the conventional 7-SNP genotype. This procedure represents a facilitation in individualized dosing of NAT2 substrates without losing sensitivity or specificity.

[The assessment of therapy success after radical prostatectomy]. / Die Beurteilung des Behandlungserfolges nach Radikaler Prostatektomie.

OBJECTIVES: Patient satisfaction plays an important role in the outcome quality of treatment for localized prostate carcinoma. This paper identifies factors that impact patients' assessment of therapy success one year after surgery. METHODS: Patient assessment of therapy success was measured with the Hamburger Fragebogen zum Krankenhausaufenthalt (Lecher et al. 2002). Also, several sociodemographic, clinical and quality-of-life factors were tested for their impact on the patient assessment of therapy success. RESULTS: 25 % of patients gave a negative assessment of therapy success. Factors with the strongest impact were urinary incontinence, sexual impotence, younger age and higher risk of recidive. CONCLUSIONS: Especially the prevention of urinary continence and sexual dysfunction may lead to a better assessment of therapy. Moreover, the patients' expectations have a great impact on the assessment of therapy success.

Rs710521[A] on chromosome 3q28 close to TP63 is associated with increased urinary bladder cancer risk.

Single nucleotide polymorphism (SNP) rs710521[A], located near TP63 on chromosome 3q28, was identified to be significantly associated with increased bladder cancer risk. To investigate the association of rs710521[A] and bladder cancer by new data and by meta-analysis including all published data, rs710521 was studied in 1,425 bladder cancer cases and 1,740 controls that had not been included in previous studies. Blood samples were collected from 1995 to 2010 in Germany (n = 948/1,258), Hungary (n = 262/65), Venezuela (n = 112/190) and Pakistan (n = 103/227) supplemented by a meta-analysis of 5,695 cases and 40,187 controls. Detection of a A/G substitution (rs710521) on chromosome 3q28, position 191128627 was done via fast real-time polymerase chain reaction (rt-PCR). Rs710521[A] is associated with increased risk in the unadjusted analysis (OR = 1.21; 95% Cl = 1.04-1.40; P = 0.011) and in the recessive model adjusted for age, gender, smoking habits and ethnicity (OR = 1.23; 95% Cl = 1.05-1.44; P = 0.010). No difference between individuals occupationally exposed versus not occupationally exposed to urinary bladder carcinogens was observed concerning the relevance of rs710521[A]. Similarly, rs710521[A] did not confer different susceptibility in smokers and non-smokers. Performing a meta-analysis of 5,695 cases and 40,187 controls including all published studies on rs710521, a convincing association with bladder cancer risk was obtained (OR = 1.18; 95% Cl = 1.12-1.25; P < 0.0001). However, the odds ratio is relatively small.

Quantitative study of mast cells in experimentally induced benign prostatic hyperplasia.

INTRODUCTION: Mast cells are involved in a number of biological responses to exocrine and endocrine stimuli, by releasing growth factors and certain cytokines. The aim of this study was to evaluate their number and distribution in experimentally induced benign prostatic hyperplasia in rats. MATERIALS AND METHODS: Adult Wistar rats (100 days old) were given citral transdermally for 1 month. Morphological characteristics and mast cell concentration were studied in proximal and distal zones after staining with hematoxylin-eosin and Giemsa, respectively. RESULTS: Citral induced mild benign prostatic hyperplasia. Mast cell numbers were increased significantly in both the proximal (2.97 +/- 0.52 vs. 1.4 +/- 0.17, p = 0.004) and distal zone (2.8 +/- 0.68 vs. 1.16 +/- 0.11, p = 0.011). CONCLUSION: Transdermal citral application resulted in a significant increase of mast cell numbers in the stroma of the rat ventral prostate. Furthermore, these mast cells were larger, contained a significant number of intracytoplasmic granules and degranulated. This finding suggests a role for mast cells in the pathogenesis of benign prostatic hyperplasia.

Secretion of soluble VEGF receptor 2 by microvascular endothelial cells derived by human benign prostatic hyperplasia.

Vascular endothelial growth factor (VEGF) is one of the most potent mitogenic factors stimulating both prostate endothelial and prostate epithelial cells. Recently, some studies reported on the endothelial secretion of a soluble VEGF receptor 2 (sVEGFR-2) that modifies the free VEGF concentration by binding VEGF. For the first time in this study, we report on the secretion and the regulation of the secretion of sVEGFR-2 by microvascular endothelial cells derived from the tissue of human benign prostatic hyperplasia (HPEC). HPEC were isolated and cultured from fresh prostate tissue. The prostate epithelial cell line BPH-1 was cultured with the supernatant of the HPEC cell culture (fractioned by fast protein liquid chromatography) and the VEGF concentration was subsequently measured. HPEC were incubated with VEGF or tumor necrosis factor alpha (TNF-alpha). Afterwards, the concentration of sVEGFR-2 in the supernatant of unstimulated and stimulated HPEC was measured by ELISA. HPEC showed a typical endothelial morphology. Under cell culture conditions sVEGFR-2 binds VEGF: The measured VEGF concentration in the supernatant of BPH-1 cells was reduced when the fractions of HPEC conditioned medium with the highest sVEGFR-2 concentration were incubated with the BPH-1 cells. The sVEGFR-2 secretion of HPEC was stimulated by VEGF and TNF-alpha. For the first time we report on the secretion of sVEGFR-2 by microvascular endothelial cells of prostate origin. The secretion of sVEGFR-2 by HPEC was stimulated by VEGF and TNF-alpha. Our data suggest that sVEGFR-2 secreted by prostate endothelial cells could modify the effect of VEGF on prostate endothelial and prostate epithelial cells.