Designing the selenium and bladder cancer trial (SELEBLAT), a phase lll randomized chemoprevention study with selenium on recurrence of bladder cancer in Belgium

<p>Abstract</p> <p>Background</p> <p>In Belgium, bladder cancer is the fifth most common cancer in males (5.2%) and the sixth most frequent cause of death from cancer in males (3.8%). Previous epidemiological studies have consistently reported that selenium concentrations were inversely associated with the risk of bladder cancer. This suggests that selenium may also be suitable for chemoprevention of recurrence.</p> <p>Method</p> <p>The SELEBLAT study opened in September 2009 and is still recruiting all patients with non-invasive transitional cell carcinoma of the bladder on TURB operation in 15 Belgian hospitals. Recruitment progress can be monitored live at <url>http://www.seleblat.org.</url> Patients are randomly assigned to selenium yeast (200 μg/day) supplementation for 3 years or matching placebo, in addition to standard care. The objective is to determine the effect of selenium on the recurrence of bladder cancer. Randomization is stratified by treatment centre. A computerized algorithm randomly assigns the patients to a treatment arm. All study personnel and participants are blinded to treatment assignment for the duration of the study.</p> <p>Design</p> <p>The SELEnium and BLAdder cancer Trial (SELEBLAT) is a phase III randomized, placebo-controlled, academic, double-blind superior trial.</p> <p>Discussion</p> <p>This is the first report on a selenium randomized trial in bladder cancer patients.</p> <p>Trial registration</p> <p>ClinicalTrials.gov identifier: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00729287">NCT00729287</a></p

Kidney radiofrequency ablation for small renal tumors : oncologic efficacy

Background and Purpose: The introduction of radiofrequency ablation (RFA) into other fields of surgery has fueled the interest to study its application in small renal masses (SRM). Some controversies remain, however, regarding its oncologic efficacy. We review technical factors and tissue characteristics that influence treatment success, discuss the evaluation of treatment success by post-treatment imaging and histopathology, and highlight intermediate-term oncologic outcomes of recent, larger RFA series. Materials and Methods: A search of the MEDLINE database regarding the treatment of SRM by RFA was performed from 2003 through August 2009. For the purpose of describing technical factors and tissue characteristics that influence treatment success and the evaluation of treatment success by imaging and histopathology, articles were selected when they provided detailed descriptions of one or more of these items. For the analysis of oncologic outcomes, the selection was limited to series in which a minimum of 20 patients were treated and that provided effectiveness based on follow-up imaging. Results: Technical evolutions and correct patient/tumor selection have led to increasingly higher success rates being achieved by RFA. Even though tumor skipping has been described in preclinical studies and early clinical studies, this does not seem to influence final success. Indeed, a 8.6% re-treatment rate has to be taken into account. Accepting this, the final ablative success rate is 93.8% at intermediate-term follow-up. Complications after RFA are less frequent and more often minor compared with surgical series. Conclusions: The present analysis reveals that RFA achieves a high intermediate-term ablative success rate when accepting a 8.6% reablation rate. Complication rates are low and mostly minor. Those facts render RFA an attractive minimally invasive treatment for SRM, especially in the growing elderly patient population with multiple comorbidities. Long-term follow-up data are expected to confirm the role of RFA in the management of SRM

The physical and antimicrobial effects of microwave heating and alcohol immersion on catheters that are reused for clean intermittent catheterisation

INTRODUCTION: Due to worldwide different health insurance policies, patients are often forced to reuse the catheters when performing Clean Intermittent Catheterisation (CIC). We have compared the physical qualities and the antimicrobial effects of two methods of reusing catheters: microwave heating and storage of the catheters in a 70% alcohol solution. The studies were performed during different lengths of time. MATERIALS AND METHODS: Three types of catheters (a standard polyvinylchloride catheter, a special polyvinylchloride catheter with flexible Ergothan tip and a prelubrified catheter), normally intended for single use, were submitted to the effect of a microwave oven (Multitech 215 High Grade and Whirlpool M220 750 W and 1000 W with rotating plate) or preservation in a 70% alcohol solution. To study the effects of microwave heating, a recipient of water was placed in the oven to spread the microwaves and to absorb the heat. The catheters were placed in a resealable plastic bag (Ziploc. To study the effects of preservation in a 70% alcohol solution, the catheters were immerged in the solution for different lengths of time. Thereafter were the physical qualities of the catheters evaluated by using the technique of Differential Scanning Calorimetry (DSC). The antimicrobial effect of the method was evaluated after grafting the catheters with pathogenic E. coli, P. aeruginosa or S. aureus strains. RESULTS: Microwave heating up to 12 minutes at 750 W caused only minimal changes in the physical qualities of all the catheters. However, there was only an antimicrobial effect of the microwave heating on E. coli and not on P. aeruginosa or S. aureus. If the catheter remained longer than 45 minutes in a 70% alcohol solution, the physical qualities of the catheter changed either minimal in the special polyvinylchloride catheter with flexible Ergothan top but changed significantly in the prelubrified catheter). However, already after 5 minutes of immersion in the 70% alcohol solution there was a complete antimicrobial effect on E. coli, P. aeruginosa and S. aureus in all catheters. CONCLUSIONS: It should be recommended to patients on CIC to use a sterile packed and not previously used catheter. In this study we have shown that immersing the catheters in a 70% alcohol solution during 5 minutes can effectively disinfect the catheter without jeopardising the physical qualities. Thereafter, the catheters could be placed in a resealable (e.g. Ziploc bag without being rinsed under water, in order that the few drops of alcohol cause alcohol vapours within the closed plastic bag and maintain the antimicrobial effect.status: publishe

Binding of temocillin to plasma proteins in vitro and in vivo: the importance of plasma protein levels in different populations and of co-medications

Background Temocillin plasma protein binding (PPB) in healthy individuals is reported to be similar to 85% but had not been studied in patients. Objectives To obtain normative data on temocillin PPB in patients in relation to infection and impact of co-medications widely used in ICU. Methods Plasma was obtained from healthy individuals (Group #1), non-ICU patients with UTI (Group #2), ICU patients with suspected/confirmed ventriculitis (Group #3) or with sepsis/septic shock (Group #4). Total and unbound temocillin concentrations were measured in spiked samples from temocillin-naive donors (in vitro) or in plasma from temocillin-treated subjects (in vivo). The impact of diluting plasma, using pharmaceutical albumin, or adding drugs potentially competing for PPB was tested in spiked samples. Data were analysed using a modified Hill-Langmuir equation taking ligand depletion into account. Results Temocillin PPB was saturable in all groups, both in vitro and in vivo. Maximal binding capacity (B-max) was 1.2-2-fold lower in patients. At 20 and 200 mg/L (total concentrations), the unbound fraction reached 12%-29%, 23%-42% and 32%-52% in Groups #2, #3, #4. The unbound fraction was inversely correlated with albumin and C-reactive protein concentrations. Binding to albumin was 2-3-fold lower than in plasma and non-saturable. Drugs with high PPB but active at lower molar concentrations than temocillin caused minimal displacement, while fluconazole (low PPB but similar plasma concentrations to temocillin) increased up to 2-fold its unbound fraction. Conclusions Temocillin PPB is saturable, 2-4-fold lowered in infected patients in relation to disease severity (ICU admission, hypoalbuminaemia, inflammation) and only partially reproducible with albumin. Competition with other drugs must be considered for therapeutic concentrations to be meaningful

Phase III randomised chemoprevention study with selenium on the recurrence of non-invasive urothelial carcinoma. The SELEnium and BLAdder cancer Trial

BACKGROUND: In Belgium, bladder cancer (BC) is the fifth most common cancer in men. The per-patient lifetime cost is high. Previous epidemiological studies have consistently reported that selenium concentrations were inversely associated with the risk of BC. We therefore hypothesised that selenium may be suitable for chemoprevention of recurrence of BC. METHOD: The Selenium and Bladder Cancer Trial (SELEBLAT) was an academic phase III placebo-controlled, double-blind, randomised clinical trial designed to determine the effect of selenium on recurrence of non-invasive urothelial carcinoma conducted in 14 Belgian hospitals. Patients were randomly assigned by a computer program to oral selenium yeast 200 μg once a day or placebo for three years, in addition to standard care. All study personnel and participants were blinded to treatment assignment for the duration of the study. All randomised patients were included in the intention to treat (ITT) and safety analyses. Per protocol analyses (PPAs) included all patients in the study three months after start date. RESULTS: Between September 18, 2009 and April 18, 2013, 151 and 141 patients were randomised in the selenium and placebo group. Patients were followed until December 31, 2015. The ITT analysis resulted in 43 (28%; 95% CI, 0.21-0.35) and 45 (32%; 95% CI, 0.24-0.40) recurrences in the selenium and placebo group. The hazard ratio (HR) was 0.85 (95% CI, 0.56-1.29; p = 0.44) while the HR for the PPA resulted in 42 and 39 (28%; 95% CI, 0.20-0.35) recurrences in the selenium and placebo group (HR = 0.96 [95% CI, 0.62-1.48]; p = 0.93). CONCLUSION: Selenium supplementation does not lower the probability of recurrence in BC patients.publisher: Elsevier articletitle: Phase III randomised chemoprevention study with selenium on the recurrence of non-invasive urothelial carcinoma. The SELEnium and BLAdder cancer Trial journaltitle: European Journal of Cancer articlelink: http://dx.doi.org/10.1016/j.ejca.2016.09.021 content_type: article copyright: © 2016 Elsevier Ltd. All rights reserved.status: publishe

Phase III randomised chemoprevention study with selenium on the recurrence of non-invasive urothelial carcinoma. The SELEnium and BLAdder cancer Trial

BACKGROUND: In Belgium, bladder cancer (BC) is the fifth most common cancer in men. The per-patient lifetime cost is high. Previous epidemiological studies have consistently reported that selenium concentrations were inversely associated with the risk of BC. We therefore hypothesised that selenium may be suitable for chemoprevention of recurrence of BC. METHOD: The Selenium and Bladder Cancer Trial (SELEBLAT) was an academic phase III placebo-controlled, double-blind, randomised clinical trial designed to determine the effect of selenium on recurrence of non-invasive urothelial carcinoma conducted in 14 Belgian hospitals. Patients were randomly assigned by a computer program to oral selenium yeast 200 μg once a day or placebo for three years, in addition to standard care. All study personnel and participants were blinded to treatment assignment for the duration of the study. All randomised patients were included in the intention to treat (ITT) and safety analyses. Per protocol analyses (PPAs) included all patients in the study three months after start date. RESULTS: Between September 18, 2009 and April 18, 2013, 151 and 141 patients were randomised in the selenium and placebo group. Patients were followed until December 31, 2015. The ITT analysis resulted in 43 (28%; 95% CI, 0.21-0.35) and 45 (32%; 95% CI, 0.24-0.40) recurrences in the selenium and placebo group. The hazard ratio (HR) was 0.85 (95% CI, 0.56-1.29; p = 0.44) while the HR for the PPA resulted in 42 and 39 (28%; 95% CI, 0.20-0.35) recurrences in the selenium and placebo group (HR = 0.96 [95% CI, 0.62-1.48]; p = 0.93). CONCLUSION: Selenium supplementation does not lower the probability of recurrence in BC patients