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Every minute counts in the event of an overdose. ETH professor Jean-Christophe Leroux and his team have developed an agent to filter out toxins from the body more quickly and efficiently.
Differences in Treatment and Outcome After Treatment with Curative Intent in the Screening and Control Arms of the ERSPC Rotterdam
Screening for prostate cancer (PCa) results in a favorable stage shift. However, even if screening did not result in a clinically apparent lower stage or grade, it might still lead to less disease recurrence after treatment with curative intent (radical prostatectomy [RP] and radiation therapy [RT]) because the tumor had less time to develop outside the prostate. The outcome after treatment could also differ because of variations in treatment quality (eg, radiation dosage/adjuvant hormonal therapy). To test these hypotheses, we compared differences in the treatment quality of the screening and control arms of the European Randomized Study of Screening for Prostate Cancer (ERSPC) Rotterdam and disease-free survival (DFS) after curative treatment in PCa patients with similar stage and grade. A total of 2595 men were initially treated with RP or RT. In the control arm, RT was more often combined with hormonal therapy; treatment dosage was often ≥69 Gy. This most likely resulted from changes over time in treatment that coincided with the later detection in the control arm. DFS was higher in the screening arm in all risk groups. After correction for lead time, these differences were minimal, however. We concluded that treatment quality differed between the screening and control arms of the ERSPC Rotterdam. RT quality was especially superior in the control arm with higher dosages and more often RT in combination with hormonal therapy. Despite these differences favoring the control arm, DFS differences were minimal.Patient summary
We looked at differences in prostate cancer (PCa) treatment and outcome after PCa treatment in men diagnosed after screening and men diagnosed after normal clinical practice. Treatment differed with superior treatment given to men diagnosed in normal clinical practice. We propose a likely explanation for this apparently counterintuitive finding (progressive insight combined with, on average, a later detection of tumors in unscreened men). Although unscreened men received better treatment, this advantage seemed to be outweighed by the advantage associated with the earlier detection, on average, of the tumor in screened men.Trial registration
ISRCTN49127736Take Home Message
The quality of similar treatments differed between the screening and control arms of the ERSPC Rotterdam, most likely related to later detection in the control arm and progressive insight. Radiation therapy (RT) quality was especially superior in the control arm with higher dosages, and RT was more often performed in combination with hormonal therapy.
Keywords: Prostatic neoplasms, Prostate-specific antigen, Screening, Radical prostatectomy, Radiotherapy, Cure rates.Footnotes
a Department of Urology, Erasmus University Medical Center, Rotterdam, the Netherlands
b Comprehensive Cancer Center, Rotterdam, The Netherlands
c Department of Pathology, Erasmus University Medical Center, Rotterdam, The Netherlands
© 2014 European Association of Urology, Published by Elsevier B.V.
The objectives of this study were to: 1) describe the patterns of repeat prostate biopsy utilization in men with previous negative biopsy, and 2) identify predictors of prostate cancer (CaP) diagnosis in these men on repeat biopsy.
A Randomised Phase 2 Trial of Intensive Induction Chemotherapy (CBOP/BEP) and Standard BEP in Poor-prognosis Germ Cell Tumours (MRC TE23, CRUK 05/014, ISRCTN 53643604)
Standard chemotherapy for poor-prognosis metastatic nonseminoma has remained bleomycin, etoposide, and cisplatin (BEP) for many years; more effective regimens are required.Objective
To explore whether response rates with a new intensive chemotherapy regimen, CBOP/BEP (carboplatin, bleomycin, vincristine, cisplatin/BEP), versus those in concurrent patients treated with standard BEP justify a phase 3 trial.Design, setting, and participants
We conducted a phase 2 open-label randomised trial in patients with germ cell tumours of any extracranial primary site and one or more International Germ Cell Cancer Collaborative Group poor-prognosis features. Patients were randomised between 2005 and 2009 at 16 UK centres.Intervention
BEP (bleomycin 30 000 IU) was composed of four cycles over 12 wk. CBOP/BEP was composed of 2 × CBOP, 2 × BO, and 3 × BEP (bleomycin 15 000 IU).Outcome measurements and statistical analysis
Primary end point was favourable response rate (FRR) comprising complete response or partial response and normal markers. Success required the lower two-sided 90% confidence limit to exclude FRRs <60%; 44 patients on CBOP/BEP gives 90% power to achieve this if the true FRR is ≥80%. Equal numbers were randomised to BEP to benchmark contemporary response rates.Results and limitations
A total of 89 patients were randomised (43 CBOP/BEP, 46 BEP); 40 and 41, respectively, completed treatment. CBOP/BEP toxicity, largely haematologic, was high (96% vs 63% on BEP had Common Terminology Criteria for Adverse Events v.3 grade ≥3). FRRs were 74% (90% confidence interval [CI], 61–85) with CBOP/BEP, 61% with BEP (90% CI, 48–73). After a median of 58-mo follow-up, 1-yr progression-free survival (PFS) was 65% and 43%, respectively (hazard ratio: 0.59; 95% CI, 0.33–1.06); 2-yr overall survival (OS) was 67% and 61%. Overall, 3 of 14 CBOP/BEP and 2 of 18 BEP deaths were attributed to toxicity, one after an overdose of bleomycin during CBOP/BEP. The trial was not powered to compare PFS.Conclusions
The primary outcome was met, the CI for CBOP/BEP excluding FRRs <61%, but CBOP/BEP was more toxic. PFS and OS data are promising but require confirmation in an international phase 3 trial.Patient summary
In this study we tested a new, more intensive way to deliver a combination of drugs often used to treat men with testicular cancer. We found that response rates were higher but that the CBOP/BEP regimen caused more short-term toxicity. Because most patients are diagnosed when their cancer is less advanced, it took twice as long to complete the trial as expected. Although we plan to carry out a larger trial, we will need international collaboration.Trial registration
ISRCTN53643604; http://www.controlled-trials.com/ISRCTN53643604 .Take Home Message
In patients with poor-prognosis metastatic germ cell tumours, this randomised phase 2 trial shows that CBOP/BEP chemotherapy (carboplatin, bleomycin, vincristine, cisplatin/bleomycin, etoposide, cisplatin) achieves superior response rates to standard BEP chemotherapy, although with increased toxicity; efficacy results require confirmation in a phase 3 trial.
Keywords: Metastatic germ cell tumour, Poor prognosis, Randomised trial.Footnotes
a The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, Sutton, UK
b Medical Research Council Clinical Trials Unit, London, UK
c Beatson West of Scotland Cancer Centre, Glasgow, UK
d St. Bartholomew's Hospital, London, UK
e University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
© 2014 European Association of Urology, Published by Elsevier B.V.
To treat the debilitating anemia associated with reduced erythropoietin (EPO) production by the kidneys in chronic renal disease, patients are often given recombinant human EPO to increase...
Evidence-based guidelines play an increasing role in setting standards for medical practice and quality but are seldom systematically evaluated in the practice setting.
Renal cell carcinoma (RCC) incidence rates are higher in developed countries, where up to half of the cases are discovered incidentally. Declining mortality trends have been reported in highly developed countries since the 1990s.Objective
To compare and interpret geographic variations and trends in the incidence and mortality of RCC worldwide in the context of controlling the future disease burden.Evidence acquisition
We used data from GLOBOCAN, theCancer Incidence in Five Continentsseries, and the World Health Organisation mortality database to compare incidence and mortality rates in more than 40 countries worldwide. We analysed incidence and mortality trends in the last 10 yr using joinpoint analyses of the age-standardised rates (ASRs).Evidence synthesis
RCC incidence in men varied in ASRs (World standard population) from approximately 1/100 000 in African countries to >15/100 000 in several Northern and Eastern European countries and among US blacks. Similar patterns were observed for women, although incidence rates were commonly half of those for men. Incidence rates are increasing in most countries, most prominently in Latin America. Although recent mortality trends are stable in many countries, significant declines were observed in Western and Northern Europe, the USA, and Australia. Southern European men appear to have the least favourable RCC mortality trends.Conclusions
Although RCC incidence is still increasing in most countries, stabilisation of mortality trends has been achieved in many highly developed countries. There are marked absolute differences and opposing RCC mortality trends in countries categorised as areas of higher versus lower human development, and these gaps appear to be widening.Patient summary
Renal cell cancer is becoming more commonly diagnosed worldwide in both men and women. Mortality is decreasing in the most developed settings, but not in low- and middle-income countries, where access to and the availability of optimal therapies are likely to be limited.Take Home Message
Renal cell carcinoma incidence is increasing worldwide. Although some progress towards stabilisation of mortality trends has been achieved globally, differences in mortality between areas of higher and lower human development levels persist.
Keywords: Kidney cancer, Trends, Incidence, Mortality, Registry.Footnotes
a Section of Cancer Surveillance, International Agency for Research on Cancer, Lyon, France
b American Cancer Society, Atlanta, GA, USA
© 2014 Published by Elsevier B.V.
The U.S. Food and Drug Administration has allowed marketing of the inFlow Intraurethral Valve-Pump, a replaceable urinary prosthesis for use in female adults who cannot contract the muscles...
Scientists are surprised to find an involuntary link in the brain between the pelvic floor and other muscles
Wherever you are right now: squeeze your glutes. Feel that? You just also contracted your pelvic floor too, whether you wanted to or not.
Neuromuscular nicotinic receptors mediate bladder contractions following bladder reinnervation with somatic to autonomic nerve transfer after decentralization by spinal root transection
This study investigates whether the reinnervated neuronal pathway mediates contraction via the same neurotransmitter and receptor mechanisms as the original pathway. Following bladder decentralization by transection of sacral roots, peripheral nerve transfer was performed with bilateral genitofemoral to pelvic nerve transfer (GFNT) and unilateral (left) femoral nerve to bilateral pelvic nerve transfer (FNT). Reinnervation was assessed 7.5 months post operatively by monitoring bladder pressure during electrical stimulation of the transferred nerves, spinal ventral roots, and spinal cord.
Re: Does this Man with Lower Urinary Tract Symptoms have Bladder Outlet Obstruction? The Rational Clinical Examination: A Systematic Review
K. A. D’Silva, P. Dahm and C. L. Wong
Re: Surgical Intervention for Symptomatic Benign Prostatic Hyperplasia is Correlated with Expression of the AP-1 Transcription Factor Network
O. Lin-Tsai, P. E. Clark, N. L. Miller, J. H. Fowke, O. Hameed, S. W. Hayward and D. W. Strand