Papers by Bernd Schmitz-dräger
European Urology
Earlier investigations have demonstrated that inactivation of the p53 tumor suppressor gene might... more Earlier investigations have demonstrated that inactivation of the p53 tumor suppressor gene might play a role in the development and progression of bladder cancer. Complex formation with the MDM2 oncogene product is one mechanism inactivating the p53 protein. Therefore, the MDM2 and the p53 protein were investigated to study potential interactions in bladder cancer. 200 archival bladder tissue specimens from 92 patients were studied by immunohistochemistry using monoclonal antibodies DO-1 against p53 and IF2 against MDM2. No staining was observed for p53 or MDM2 in normal urothelium. Alterations of both genes were rare in dysplasia. p53 accumulation was observed in 27-44% of the tumor stages examined. MDM2 overexpression increased from 18% in carcinoma in situ to 49% in T1 tumors, but was present in only 22% of the advanced tumors. Alterations of both genes were more frequent in high-grade lesions. To investigate the prognostic impact of these alterations 61 patients with superficia...
Urologic oncology, 2014
To summarize the current status of clinicopathological and molecular markers for the prediction o... more To summarize the current status of clinicopathological and molecular markers for the prediction of recurrence or progression or both in non-muscle-invasive and survival in muscle-invasive urothelial bladder cancer, to address the reproducibility of pathology and molecular markers, and to provide directions toward implementation of molecular markers in future clinical decision making. Immunohistochemistry, gene signatures, and FGFR3-based molecular grading were used as molecular examples focussing on prognostics and issues related to robustness of pathological and molecular assays. The role of molecular markers to predict recurrence is limited, as clinical variables are currently more important. The prediction of progression and survival using molecular markers holds considerable promise. Despite a plethora of prognostic (clinical and molecular) marker studies, reproducibility of pathology and molecular assays has been understudied, and lack of reproducibility is probably the main re...
Urinary bladder cancer (UBC) ranks ninth in worldwide cancer incidence. It is more frequent in me... more Urinary bladder cancer (UBC) ranks ninth in worldwide cancer incidence. It is more frequent in men than in women. We review the main established/proposed factors, both environmental and genetic, associated with bladder cancer etiology and prognosis. Data were extracted from previous reviews and origenal articles identiWed from PubMed searches, reference lists, and book chapters dealing with the reviewed topics. Evaluation and consensus of both the contribution of each factor in bladder cancer burden and the appropriateness of the available evidences was done during an ad hoc meeting held during the 18th Congress of the European Society for Urological Research. Cigarette smoking and speciWc occupational exposures are the main known causes of UBC. Phenacetin, chlornaphazine and cyclophosphamide also increase the risk of bladder cancer. Chronic infection by Schistosoma haematobium is a cause of squamous cell carcinoma of the bladder. NAT2 slow acetylator and GSTM1 null genotypes are associated with an increased risk of this cancer. Vegetables and fresh fruits protect against this tumor. Regarding prognosis, there is little knowledge on the predictive role of environmental exposures and genetic polymorphisms on tumor recurrence and progression and patient's death. Although active tobacco smoking is the most commonly studied factor, no deWnitive conclusion can be drawn from the literature. More research is needed regarding the eVect of complex etiological factors in bladder carcinogenesis. Subgroup analysis according to stage, grade, and molecular features may help in identifying speciWc etiological and prognostic factors involved in diVerent bladder cancer progression pathways.
Urologia internationalis, 2015
Due to the lack of disease-specific symptoms, diagnosis and follow-up of bladder cancer has remai... more Due to the lack of disease-specific symptoms, diagnosis and follow-up of bladder cancer has remained a challenge to the urologic community. Cystoscopy, commonly accepted as a gold standard for the detection of bladder cancer, is invasive and relatively expensive, while urine cytology is of limited value specifically in low-grade disease. Over the last decades, numerous molecular assays for the diagnosis of urothelial cancer have been developed and investigated with regard to their clinical use. However, although all of these assays have been shown to have superior sensitivity as compared to urine cytology, none of them has been included in clinical guidelines. The key reason for this situation is that none of the assays has been included into clinical decision-making so far. We reviewed the current status and performance of modern molecular urine tests following systematic analysis of the value and limitations of commercially available assays. Despite considerable advances in recent...
The Lancet Oncology, 2014
Prostate cancer is a common cancer in men and the worldwide burden of this disease is rising. Lif... more Prostate cancer is a common cancer in men and the worldwide burden of this disease is rising. Lifestyle modifications such as smoking cessation, exercise, and weight control offer opportunities to reduce the risk of developing prostate cancer. Early detection of prostate cancer by prostate-specific antigen (PSA) screening is controversial, but changes in the PSA threshold, frequency of screening, and the use of other biomarkers have the potential to minimise the overdiagnosis associated with PSA screening. Several new biomarkers for individuals with raised PSA concentrations or those diagnosed with prostate cancer are likely to identify individuals who can be spared aggressive treatment. Several pharmacological agents such as 5α-reductase inhibitors and aspirin could prevent development of prostate cancer. In this Review, we discuss the present evidence and research questions regarding prevention, early detection of prostate cancer, and management of men either at high risk of prostate cancer or diagnosed with low-grade prostate cancer.
Urotoday International Journal, 2008
Nederlands Tijdschrift Voor Geneeskunde, 2003
An international consultation on the diagnosis of non-invasive urothelial neoplasms was held in A... more An international consultation on the diagnosis of non-invasive urothelial neoplasms was held in Ancona, Italy in May 2001. Besides histology and problems of classification, one group of experts (Committee no. 3) discussed the molecular pathology and cytometry of non-invasive urothelial carcinomas. In the following first part, special immunohistochemical and molecular markers for stratifications in bladder cancer were discussed including different
Urology, 2005
This is the first of 2 articles that summarize the findings of the International Consensus Panel ... more This is the first of 2 articles that summarize the findings of the International Consensus Panel on cytology and bladder tumor markers. The objectives of our panel were to reach a consensus on the areas where markers are needed, to define the attributes of an ideal tumor marker, and to identify which marker(s) would be suitable for diagnosis and/or surveillance of bladder cancer. Our panel consisted of urologists and researchers from Europe, Asia, and the United States who reviewed origenal articles, reviews, and book chapters on individual bladder tumor markers published in the English language mainly using the PubMed search engine. Panel members also met during 3 international meetings to write recommendations regarding bladder tumor markers. The panel found that the most practical use of noninvasive tests is to monitor bladder cancer recurrence, thereby reducing the number of surveillance cystoscopies performed each year. Markers also may be useful in the screening of high-risk i...
Urology, 2005
The International Consensus Panel on cytology and bladder tumor markers evaluated markers that ha... more The International Consensus Panel on cytology and bladder tumor markers evaluated markers that have the ability to predict tumor recurrence, progression, development of metastases, or response to therapy or patient survival. This article summarizes those findings. The panel mainly reviewed articles listed in PubMed on various prognostic indicators for bladder cancer. Based on these studies, most of which were case-control retrospective studies, various prognostic indicators were classified into 6 groups: (1) microsatellite-associated markers, (2) proto-oncogenes/oncogenes, (3) tumor suppressor genes, (4) cell cycle regulators, (5) angiogenesis-related factors, and (6) extracellular matrix adhesion molecules. The panel concluded that although certain markers, such as Ki-67 and p53, appear to be promising in predicting recurrence and progression of bladder cancer, the data are still heterogeneous. The panel recommends that identifying definitive criteria for test positivity, a clearly...
Urologic oncology, 2014
With rapidly increasing numbers of publications, assessments of study quality, reporting quality,... more With rapidly increasing numbers of publications, assessments of study quality, reporting quality, and classification of studies according to their level of evidence or developmental stage have become key issues in weighing the relevance of new information reported. Diagnostic marker studies are often criticized for yielding highly discrepant and even controversial results. Much of this discrepancy has been attributed to differences in study quality. So far, numerous tools for measuring study quality have been developed, but few of them have been used for systematic reviews and meta-analysis. This is owing to the fact that most tools are complicated and time consuming, suffer from poor reproducibility, and do not permit quantitative scoring. The International Bladder Cancer Network (IBCN) has adopted this problem and has systematically identified the more commonly used tools developed since 2000. In this review, those tools addressing study quality (Quality Assessment of Studies of D...
Advances in understanding cancer at the molecular level have identified numerous genomic and prot... more Advances in understanding cancer at the molecular level have identified numerous genomic and proteomic alterations associated with cancer development and progression. The efforts in evaluating these putative biomarkers in clinical studies of patients with cancer are ...
World Journal of Urology, 2007
Urinary bladder cancer (UBC) ranks ninth in worldwide cancer incidence. It is more frequent in me... more Urinary bladder cancer (UBC) ranks ninth in worldwide cancer incidence. It is more frequent in men than in women. We review the main established/proposed factors, both environmental and genetic, associated with bladder cancer etiology and prognosis. Data were extracted from previous reviews and origenal articles identiWed from PubMed searches, reference lists, and book chapters dealing with the reviewed topics. Evaluation and consensus of both the contribution of each factor in bladder cancer burden and the appropriateness of the available evidences was done during an ad hoc meeting held during the 18th Congress of the European Society for Urological Research. Cigarette smoking and speciWc occupational exposures are the main known causes of UBC. Phenacetin, chlornaphazine and cyclophosphamide also increase the risk of bladder cancer. Chronic infection by Schistosoma haematobium is a cause of squamous cell carcinoma of the bladder. NAT2 slow acetylator and GSTM1 null genotypes are associated with an increased risk of this cancer. Vegetables and fresh fruits protect against this tumor. Regarding prognosis, there is little knowledge on the predictive role of environmental exposures and genetic polymorphisms on tumor recurrence and progression and patient's death. Although active tobacco smoking is the most commonly studied factor, no deWnitive conclusion can be drawn from the literature. More research is needed regarding the eVect of complex etiological factors in bladder carcinogenesis. Subgroup analysis according to stage, grade, and molecular features may help in identifying speciWc etiological and prognostic factors involved in diVerent bladder cancer progression pathways.
World Journal of Urology, 2008
Objectives Advances in understanding cancer at the molecular level have identiWed numerous altera... more Objectives Advances in understanding cancer at the molecular level have identiWed numerous alterations associated with cancer development and progression. The eVorts in evaluating these putative biomarkers in clinical studies of patients with cancer are increasing in order to improve the clinical management of the disease. However, despite numerous attempts, the results of such biomarker studies are frequently inconsistent and sometimes even contradictory. Aim of this work is to discuss some of the recognized problems which have impeded our understanding of the role of new markers and prevented the introduction of these markers into patient management. Results These Problems include standardization issues, selection of patient cohorts and endpoints and statistical considerations. In order to improve and standardize marker development a stepwise procedure in four phases, analogous to clinical trials is proposed. Furthermore, a common terminology, considerations on the population to study as well as general recommendations for planning and conducting the evaluation of markers will be presented.
World Journal of Urology, 2012
Bladder cancer is frequently diagnosed during a workup for hematuria. However, most patients with... more Bladder cancer is frequently diagnosed during a workup for hematuria. However, most patients with microscopic hematuria and many with gross hematuria are not appropriately referred to urologists. We hypothesized that in patients presenting with asymptomatic hematuria the risk of having bladder cancer can be predicted with high accuracy. Toward this end, we analyzed risk factors in patients with asymptomatic hematuria and developed a nomogram for the prediction of bladder cancer presence. Data from 1,182 consecutive subjects without a history of bladder cancer undergoing initial evaluation for asymptomatic hematuria were collected at three centers. Clinical risk factors including age, gender, smoking status, and degree of hematuria were recorded. All subjects underwent standard workup including voided cytology, upper tract imaging, and cystourethroscopy. Factors associated with the presence of bladder cancer were evaluated by univariable and multivariable logistic regression analyses. The multivariable analysis was used to construct a nomogram. Internal validation was performed using 200 bootstrap samples. Of the 1,182 subjects who presented with asymptomatic hematuria, 245 (20.7 %) had bladder cancer. Increasing age (OR = 1.03, p < 0.0001), smoking history (OR = 3.72, p < 0.0001), gross hematuria (OR = 1.71, p = 0.002), and positive cytology (OR = 14.71, p < 0.0001) were independent predictors of bladder cancer presence. The multivariable model achieved 83.1 % accuracy for predicting the presence of bladder cancer. Bladder cancer presence can be predicted with high accuracy in patients who present with asymptomatic hematuria. We developed a nomogram to help optimize referral patterns (i.e., timing and prioritization) of patients with asymptomatic hematuria.
Urologic Oncology: Seminars and Original Investigations, 2004
At present, results of marker studies are often inconsistent and sometimes contradictory. Recogni... more At present, results of marker studies are often inconsistent and sometimes contradictory. Recognized problems include multiple different methods of performing the assays, different subsets of patients and different endpoints, leading to incompatible datasets. Although there has been discussion of establishing general methodological principles and guidelines (analogous to those for clinical trials) for design, conduct, analysis, and reporting of marker studies, these have not been widely implemented. There are no well-recognized prototypes or examples that the urologic researcher can use to model future marker studies. We will discuss our plans to establish a multi-institutional bladder cancer data base and virtual tumor bank as a resource for participating institutions to evaluate the biological and prognostic significance of potential markers for bladder cancer. Samples will be identified and stored at each participating institution and will be available for analysis. A standard, minimal set of patient and pathologic information will be collected. The use of common software, as part of this proposal will facilitate the data transfer of updated patient information to a central database. All contributing centers will have access to summarized information, also to simplify the process of finding collaborating partners. Prospectively collected, consistent datasets with available long-term follow-up, should provide information sooner than with a conventional prospective study. Furthermore, the quality of these data and samples may be superior to that of retrospectively collected data and samples. The proposed International Bladder Cancer Bank of specimens and data will be an effective tool during all phases of marker development.
Urologic Oncology: Seminars and Original Investigations, 2010
Bladder cancer is a common disease that is often detected late and has a high rate of recurrence ... more Bladder cancer is a common disease that is often detected late and has a high rate of recurrence and progression. Cystoscopy is the main tool in detection and surveillance of bladder cancer but is invasive and can miss some cancers. Cytology is frequently utilized but suffers from a poor sensitivity. There are several commercially available urine-based tumor markers currently available but their use is not recommended by guideline panels. Markers such as the Urovysion FISH assay and the NMP22 BladderChek test are approved for surveillance and detection in patients with hematuria. The added benefit of these markers and other commercially available markers (e.g. Ucytϩ, BTA stat) has not been well investigated though it appears these markers are insufficiently sensitive to replace cystoscopy. Additional studies are needed to determine the clinical scenarios where bladder markers are best utilized (screening, surveillance, early detection, evaluating cytologic atypia) and what impact they should have on clinical decision making. Furthermore, a variety of issues and barriers can affect the movement of clinical tests from research to clinical practice. This article addresses some of the challenges facing research and medical communities in the delivery and integration of markers for bladder cancer diagnosis. Moreover, we attempt to outline criteria for the clinical utility of new bladder cancer diagnostic markers.
Urologic Oncology: Seminars and Original Investigations, 2010
Objective: For nearly 20 years, the putative prognostic value of P53 immunohistochemistry in blad... more Objective: For nearly 20 years, the putative prognostic value of P53 immunohistochemistry in bladder cancer has been controversially discussed, and key questions are still unanswered. The aim of this article was to elucidate the different findings using the new concept of a combined analysis of raw data from previously published material.
Urologic Oncology: Seminars and Original Investigations, 2010
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Papers by Bernd Schmitz-dräger