The department of Urology of Erasmus MC focuses on translational research in various subspecialities in Urology (oncology, functional urology, andrology, pediatric urology, stone disease). Each of these subspecialities has its preclinical research laboratory, and findings are validated in the clinic. In order to facilitate (pre-)clinical research, a Trial and Research Coordination organizes the initiation of clinical trials, patient monitoring, and statistical analysis of data. Large data and biomaterial sets have been build up carefully over the last twenty years, especially for prostate and bladder cancer. The department is top-ranked within Erasmus MC with regard to its scientific output.
A number of research projects have been formulated below. Principle investigators can be contacted for further information directly by email, copying the chairman of Urology, Prof Chris H. Bangma, and the Coordinator of Education Mrs Merit Domscheit.
Theme 1: my assay smells cancer prognosis…
Prof. dr. Chris Bangma
Biomarkers indicating aggressive prostate cancer
Prostate cancer shows a large variation in biologic and clinical growth. Current markers like Gleason score (histologic grading) and PSA (prostate specific antigen in serum) are inadequate to predict the biologic behaviour of a cancer at the time of diagnosis. Therefore, the choice for a tailored therapy, whether by surgery, by radiotherapy, or by active surveillance avoiding invasive therapy, is complex.
Preclinical research has identified candidate prognostic biomarkers in serum and laboratory models (Dr Guido Jenster, Dr Theo Luider, the results of a research project from the European P-mark consortium led by Erasmus Urology). These markers need to be validated in the large biobanks of patient sera. We have made a priority listing of candidate markers according to their biologic relevance and other criteria. For these markers we need to construct simple antibody based assays (ELISA) that can test a large set of patient sera simultaneously.
What are you going to do?
The student will observe the diagnostic and therapeutic procedures of a number of prostate cancer patients in outpatient clinic, the clinic, in operation theatre or while being irradiated. Next, the database with long term follow-up of over 500 patients that underwent radical prostatectomy will be analysed for survival and treatment effects in the trial and research unit (Dr Mark Wildhagen). The outcomes will be compared with the literature, and form the base of a manuscript. The biomaterials of these patients will serve for the analysis of new biomarkers. The student will construct a new ELISA assay in the laboratory (Dr Guido Jenster), and perform the testing. The biomarker results will be correlated with the biological outcome of the patients from the database.
Theme 2: Botox for Bladders
Dr. Bertil Blok
Research programs in Functional Urology
During the last decade, our understanding of the control of the urinary bladder and its sphincter has been increased exponentially. Concomitantly, major improvements have been achieved in diagnostic and therapeutic possibilities and in patient management and outcome. Basic animal experiments and functional imaging techniques in humans have shown which areas of the brain are involved in the control of the bladder, and which areas are dysfunctional in incontinence. Clinically, the introduction of botulinum toxin A (Botox) injections in the bladder has prevented renal insufficiency in many patients with spinal cord injury and decreased the need for major abdominal surgery in case of urinary deviation. Furthermore, stress and urge incontinence can be treated sufficiently with minimal invasive surgery and extended release oral medication, respectively.
The focus of this research theme is on translational research. This means ideally that the main answers acquired from basic research questions are used directly for clinical application. The student will participate and interact with research groups of other investigators of urology and other clinical departments, like radiology. This research theme comprises both experimental and clinical aspects.
- Study of the effects of botulinum toxin A on the lower urinary tract of rats.
- Bone marrow stem cell myogenic differentiation for implantation in the lower urinary tract of rats.
- Functional imaging of the effects of anti-cholinergics used in urge incontinence.
- Functional imaging of the effects of anti-androgens used in prostate cancer.
- Treatment evaluation of new anti-incontinence devices.
Theme 3: Nuts and male (sub)fertility
Dr. Gert Dohle, Prof. dr. Regine P.M. Steegers-Theunissen
The relationship between dietary factors and sperm parameters
Male subfertility is present in 30-50% of subfertile couples and is unexplained in 75% of cases. Usually, the patient presents with poor sperm quality (oligo-asteno-teratozoospermia OAT syndrome) without obvious health problems or medical history that can explain the impaired sperm parameters. Potential explanations for idiopatic OAT are testicular dysgenesis caused by gene-environment interactions in early pregnancy, genetic defects such as an abnormal karyotype or Y-chromosome deletion, obesity and life-style factors like the use of anabolic steroids, and nutritional factors.
Based on the literature it is postulated that certain nutritional factors and dietary patterns may be associated with abnormal spermatogenesis.
What are you going to do?
An analysis is performed of a database containing medical history, food frequency questionnaires, physical examination, scrotal ultrasound and the results of semen analysis, including DNA-fragmentation of spermatozoa.
The goal is to detect dietary factors/patterns that are associated with male subfertility and increased DNA damage. This may result in randomised placebo controlled intervention studies to determine the influence on sperm quality and pregnancy rates.
Theme 4: Sperm morphology and DNA-damage. Can we predict male fertility?
Dr. Gert Dohle
Male infertility is present in 30-50% of infertile couples and is unexplained in 75% of cases. Usually, the patient presents with poor sperm quality (oligo-asteno-teratozoospermia) for which there is no evidence based treatment. The couples are offered artificial reproductive techniques (ART) such as in vitro fertilisation and intracytoplasmic sperm injection. Sperm count and motility score are limited predictors of spontaneous pregnancy and the results of ART. Sperm morphology and sperm DNA damage may be better predictors of fertilisation rate and pregnancy.
What are you going to do?
First we start with an analysis of the predictive value of sperm morphology according to the kruger Strict criteria and the WHO-criteria. Data are extracted from semen analysis performed since 2004 and the outcome of ART in our IVF lab. Secondly, we will perform sperm chromatine structure analysis (SCSA) on specimens containing different levels of normal morphology before and after sperm preparation for IVF/ICSI. Also morphology is repeated after sperm preparation and compared to the pre-preparation specimen and the SCSA data. Finally we hope to answer the question if sperm DNA damage (SCSA) is a better predictor for spontaneous pregnancy and the results of ART.
Theme 5: PSA based prostate cancer screening, pitfalls and possible improvements
Dr. Monique Roobol
The European Randomized study of Screening for Prostate Cancer (ERSPC) is designed to study the effects of prostate-specific antigen (PSA) driven prostate cancer (PC) screening on PC-mortality. By November 2006 a total of 276,949 men have been randomized between a screening and control arm in 8 European countries. Next to the main endpoint, the study of prostate cancer mortality, prostate cancer morbidity, the value of the screening procedures, and quality of life in the screening and control arms are subject to investigation.
The ERSPC screening study applied a PSA based screening algorithm i.e. the trigger for further evaluation (prostate biopsy) was solely based on the outcome of the PSA test. This has resulted in a considerable percentage of unnecessary tests and is considered one of the drawbacks of population based prostate cancer screening.
Currently there is no population based screening program, in fact offering screening for prostate cancer is not illegal. However PSA testing on request is quite common. A better risk stratification enabling better guidance for both physician and patient is therefore warranted.
What are you going to do?
The student will assess the outcomes of the screening process and will focus in particular on repeat screening rounds. With the available data an attempt will be made to develop a more efficient screening algorithm especially suitable for men with repeated negative test results in the past. To achieve this goal the student will work with large databases and perform advanced statistical analyses developing multivariable models to predict biopsy outcome. Next to this the student will have the opportunity to actively participate within the ongoing studies and the screening program of ERSPC. This will entail blood drawing, DRE and TRUS examinations and prostate biopsies of men randomised to the screening arm of the ERSPC.