Current practice in the management of superficial bladder cancer in the Netherlands and Belgian Flanders: a survey

OBJECTIVE: Because there is no national guideline for the diagnosis, therapy and follow up of (superficial) bladder cancer in the Netherlands and Belgium, the actual patient management may differ between urologists. The purpose of this study is to get insight in the current way urologists diagnose, treat and follow patients with superficial bladder cancer. METHODS: All practising urologists in the Netherlands (n = 293) and Flemish speaking Belgium (Flanders, n = 223) received a questionnaire with regard to the current management of patients with superficial bladder cancer. The results were compared with the guidelines provided by the European Association of Urology (EAU). Also a comparison was made between the two countries and between university and community hospitals. RESULTS: The results show a wide variation in current practice for superficial bladder cancer. Although the majority of urologists do not follow the EAU guidelines, current practice roughly matches these guidelines. There are no major differences between the two countries or between different types of hospitals. Discrepancies between current practice and guidelines are mostly too frequent use of techniques for the diagnosis, treatment and follow-up. CONCLUSION: In all, there is a need for clear guidelines in superficial bladder cancer and an effective implementation of such guidelines into everyday practice.     

Post-void residual urine volume is not a good predictor of the need for invasive therapy among patients with benign prostatic hyperplasia

PURPOSE: We assessed the value of baseline PVR as predictor of the need for invasive therapy during long-term followup of patients with clinical BPH treated initially with alpha1-blockers or WW. MATERIALS AND METHODS: The records of a cohort of 942 patients with BPH treated with alpha(1)-blockers or WW were reviewed. Baseline I-PSS scores, PSA, prostate volume, uroflowmetry, pressure flow parameters and followup data were collected prospectively. Correlations between PVR and other baseline parameters were calculated. The 5-year cumulative risks of invasive therapy were calculated with the Kaplan-Meier method. After stratification of PVR by various cutoff levels (50, 100 and 300 ml), rate ratios between large and small PVRs were calculated using proportional hazards analyses. RESULTS: PVR has weak (-0.2相似文献   

Alcohol consumption and risk of prostate cancer in middle-aged men

Alcohol consumption is a modifiable lifestyle factor that may affect prostate cancer risk. Alcohol alters the hormonal milieu and contains chemical substances such as flavonoids (red wine), which may alter tumor cell growth. Data from a population-based case-control study in King County, WA, were utilized to evaluate the association of alcohol consumption with prostate cancer in middle-aged men. A total of 753 newly diagnosed prostate cancer cases, 40-64 years of age, participated in the study. Seven hundred three control subjects, frequency matched to cases by age, were selected through random digit dialing. All participants completed an in-person interview on lifetime alcohol consumption and other risk factors for prostate cancer. Logistic regression models were used to estimate odds ratios (OR) and assess significance (95% confidence intervals [CI]). All tests of statistical significance were two-sided. No clear association with prostate cancer risk was seen for overall alcohol consumption. Each additional glass of red wine consumed per week showed a statistically significant 6% decrease in relative risk (OR = 0.94; 95% CI = 0.90-0.98), and there was evidence for a decline in risk estimates across increasing categories of red wine intake (trend p = 0.02). No clear associations were seen for consumption of beer or liquor. Our present study suggests that consumption of beer or liquor is not associated with prostate cancer. There may be, however, a reduced relative risk associated with increasing level of red wine consumption. Further research is needed to evaluate the potential negative association between red wine intake and prostate cancer risk.     

A Dynamical Systems Analysis of the Indirect Response Model with Special Emphasis on Time to Peak Response

In this paper we present a mathematical analysis of the four classical indirect response models. We focus on characteristics such as the evolution of the response R(t) with time t, the time of maximal/minimal response T_max and the area between the response and the baseline AUC_R, and the way these quantities depend on the drug dose, the dynamic parameters such as E_max and EC₅₀ and the ratio of the fractional turnover rate k_out to the elimination rate constant k of drug in plasma. We find that depending on the model and on the drug mechanism function, T_max may increase, decrease, decrease and then increase, or stay the same, as the drug dose is increased. This has important implications for using the shift in T_max as a diagnostic tool in the selection of an appropriate model     

Periprostatic fat correlates with tumour aggressiveness in prostate cancer patients

Study Type – Prognostic (case series)
Level of Evidence 4 What’s known on the subject? and What does the study add? Nowadays more and more publications have been published about the topic prostate cancer aggressiveness and obesity with mixed results. However, most of the publications used the BMI as a marker for obesity, while the most metabolic active fat is the visceral fat. To learn more about these relations we measured and used the visceral fat in our paper.

OBJECTIVE

? To examine if the periprostatic fat measured on computed tomography (CT) correlates with advanced disease we examined patients who received radiotherapy for localized prostate cancer. Several USA reports found a positive association between obesity and prostate cancer aggressiveness. However, in recent European studies these conclusions were not confirmed. Studies concerning this issue have basically relied on body mass index (BMI), as a marker of general obesity. Visceral fat, however, is the most metabolically active and best measured on CT.

PATIENTS AND METHODS

? In 932 patients, who were treated with external radiotherapy (N= 311) or brachytherapy (N= 621) for their T1‐3N0M0 prostate cancer, different fat measurements (periprostatic fat, subcutaneous fat thickness) were performed on a CT. ? Associations between the different fat measurements and risk of having high‐risk (according to Ash et al., PSA > 20 or Gleason score ≥8 or T3) disease was measured.

RESULTS

? The median age (IQR) was 67.0 years (62.0–71.0) and median BMI (IQR) was 25.8 (24.2–28.3). Logistic regression analyses, adjusted for age, revealed a significant association between periprostatic fat density (PFD) and risk of having a high risk disease. (Odds ratio [95% CI] 1.06 [1.04–1.08], P < 0.001)

CONCLUSION

? Patients with a higher PFD had more often aggressive prostate cancer.     

Effect of tyrosine kinase inhibitor treatment of renal cell carcinoma on the accumulation of carbonic anhydrase IX‐specific chimeric monoclonal antibody cG250

What’s known on the subject? and What does the study add? TKI combined with chemotherapy has shown significant synergistic activity in glioma, colon‐, and breast carcinoma, possibly through improved delivery of therapeutic molecules through vascular normalization and reduced tumour interstitial fluid pressure. Whether this can be achieved with larger molecules such as antibodies is unclear. Possibly, a narrow time window exists in which lowered interstitial fluid pressures precedes tumour vasculature destruction during which enhanced antibody uptake and synergy might be achieved. Here we show that careful timing will be necessary because the TKI‐induced tumour‐vessel destruction is swift and prevents adequate antibody accumulation.

OBJECTIVE

To investigate the effect of three different tyrosine kinase inhibitors (TKIs) on the biodistribution of chimeric monoclonal antibody (mAb) cG250, which identifies carbonic anhydrase IX (CAIX), in nude mice bearing human renal cell carcinoma (RCC) xenografts. TKIs represent the best, but still suboptimal treatment for metastatic RCC (mRCC) and combined therapy or sequential therapy might be beneficial. CAIX is abundantly over expressed in RCC and clinical trials have shown abundant and specific tumour accumulation of cG250. Combining a TKI with mAb cG250, involved in a different effector mechanism, might lead to improved tumour responses and survival in patients with mRCC.

MATERIALS AND METHODS

Nude mice bearing human RCC xenografts were treated orally with 0.75 mg/day sunitinib, 1 mg/day vandetanib, 1 mg/day sorafenib or vehicle control for 7 or 14 days. At 7 days, mice were injected i.v. with 185 kBq/5 µg ¹²⁵I‐cG250. Mice were killed at predetermined days and cG250 biodistribution was determined. Tumours were analysed by immunohistochemistry for the presence of endothelial cells, laminin, smooth muscle actin, CAIX expression and uptake of mAb cG250.

RESULTS

While on TKI treatment, tumour uptake of cG250 decreased dramatically, tumour growth was slightly inhibited and vascular density decreased considerably as judged by various markers. When treatment was stopped at 7 days, there was robust neovascularization, mainly at the tumour periphery. Consequently, cG250 uptake also recovered, albeit cG250 uptake appeared to be restricted to the tumour periphery where vigorous neovascularization was visible.

CONCLUSIONS

Simultaneous administration of a TKI and mAb cG250 severely compromised mAb accumulation. However, shortly after discontinuation of TKI treatment mAb accumulation was restored. Combined treatment strategies with TKI and mAb should be carefully designed.     

High-throughput genotyping with infrared fluorescence allele specific hybridization (iFLASH): a simple, reliable and low-cost alternative

OBJECTIVES: To develop and validate a novel genotyping approach, named infrared Fluorescence Allele Specific Hybridization (iFLASH), which combines the principles of allele specific oligonucleotide (ASO) hybridization with the advanced possibilities of infrared imaging. DESIGN AND METHODS: As an example, we genotyped the 55L > M and the 192Q > R common genetic variants of the paraoxonase-1 gene in 92 DNA samples using the iFLASH technique, and validated the outcomes with the restriction fragment length polymorphism (RFLP) and TAQman genotyping assays. RESULTS: There was a 100 percent agreement in genotype outcome among the three methods. CONCLUSIONS: Although we found complete unity in genotype outcome, the iFLASH assay has essential advantages over the RFLP and TAQman genotyping assays. First, the iFLASH technique is capable of handling up to 1536 samples per assay, which makes it a suitable technique for high-throughput genotyping. Secondly, because the costs per assay are lower, high-throughput genotyping with iFLASH is affordable.     

The effect of an active on-ward participation of hospital pharmacists in Internal Medicine teams on preventable Adverse Drug Events in elderly inpatients: protocol of the WINGS study (Ward-oriented pharmacy in newly admitted geriatric seniors)

Background

The potential of clinical interventions, aiming at reduction of preventable Adverse Drug Events (preventable ADEs) during hospital stay, have been studied extensively. Clinical Pharmacy is a well-established and effective service, usually consisting of full-time on-ward participation of clinical pharmacists in medical teams. Within the current Hospital Pharmacy organisation in the Netherlands, such on-ward service is less feasible and therefore not yet established. However, given the substantial incidence of preventable ADEs in Dutch hospitals found in recent studies, appears warranted. Therefore, "Ward-Oriented Pharmacy", an on-ward service tailored to the Dutch hospital setting, will be developed. This service will consist of multifaceted interventions implemented in the Internal Medicine wards by hospital pharmacists. The effect of this service on preventable ADEs in elderly inpatients will be measured. Elderly patients are at high risk for ADEs due to multi-morbidity, concomitant disabilities and polypharmacy. Most studies on the incidence and preventability of ADEs in elderly patients have been conducted in the outpatient setting or on admission to a hospital, and fewer in the inpatient setting. Moreover, recognition of ADEs by the treating physicians is challenging in elderly patients because their disease presentation is often atypical and complex. Detailed information about the performance of the treating physicians in ADE recognition is scarce.

Methods/Design

The design is a multi-centre, interrupted time series study. Patients of 65 years or older, consecutively admitted to Internal Medicine wards will be included. After a pre-measurement, a Ward-Oriented Pharmacy service will be introduced and the effect of this service will be assessed during a post-measurement. The primary outcome measures are the ADE prevalence on admission and ADE incidence during hospital stay. These outcomes will be assessed using structured retrospective chart review by an independent expert panel. This assessment will include determination of causality, severity and preventability of ADEs. In addition, the extent to which ADEs are recognised and managed by the treating physicians will be considered.

Discussion

The primary goal of the WINGS study is to assess whether a significant reduction in preventable ADEs in elderly inpatients can be achieved by a Ward-Oriented Pharmacy service offered. A comprehensive ADE detection method will be used based on expert opinion and retrospective, trigger-tool enhanced, chart review.

Trial registration

ISRCTN: ISRCTN64974377