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ABSTRACT: Das prostataspezifische Antigen (PSA) ist die wichtigste Kenngröße in der Diagnostik und Therapieüberwachung des Prostatakarzinoms.
Zur besseren Abgrenzung zwischen benigner Prostatahyperplasie (BPH) und Prostatakarzinom, aber auch zur Früherkennung des
Prostatakarzinoms haben sich die molekularen Formen des PSA und neuerdings auch das humane Kallikrein 2 (hK2) als wertvolle
Entscheidungshilfen erwiesen.
Es wird eine Literaturübersicht über bisher vorliegende Informationen zur Aussagekraft des freien PSA (fPSA) in Relation zum
Gesamt-PSA (tPSA), des an α1-Antichymotrypsin gebundenen PSA (ACT-PSA) und des komplexierten PSA (cPSA) zusammen mit eigenen
Resultaten gegeben.
Der Quotient fPSA/tPSA (fPSA%) hat sich bereits als eine wichtige Entscheidungsgröße in der urologischen Praxis etabliert,
mit der Sensitivität und Spezifität der Prostatakarzinomdiagnostik verbessert werden. Die Zahl von Prostatastanzbiopsien im
tPSA-Bereich 4–10 μg/l kann damit reduziert und bei tPSA-Werten <4 μg/l können zusätzlich unerkannte Karzinompatienten identifiziert
werden. Ein diagnostischer Vorteil der alleinigen Bestimmung des gebundenen PSA bzw. der entsprechenden Quotienten (ACT-PSA/tPSA
oder cPSA/tPSA) im Vergleich zum fPSA% konnte bisher nicht sicher nachgewiesen werden. Die Bestimmungen der anderen molekularen
PSA-Formen und des hK2 sind noch weitgehend Gegenstand der Forschung bzw. erfordern noch entsprechende klinische Evaluierungen.
Prostate-specific antigen (PSA) is the most useful marker in the early detection of prostate cancer and in the monitoring
of patients with this diagnosis. Molecular forms of PSA and human kallikrein 2 (hK2) have been used to discriminate between
benign prostatic hyperplasia and prostate cancer, as well as for the detection of prostate cancer within the gray zone of
PSA.
In this respect, a literature survey on the diagnostic validity of free PSA (fPSA) related to total PSA (tPSA), PSA bound
to α1-antichymotrypsin (ACT-PSA), and complexed PSA (cPSA) is given together with our own results.
The ratio of fPSA/tPSA has been shown to improve both sensitivity and specificity of prostate cancer diagnosis based on tPSA
measurements. The number of biopsies can be reduced in the total PSA range of 4–10 μg/l. Furthermore, carcinomas can be detected
in patients with PSA values less than 4 μg/l. ACT-PSA or cPSA alone and the calculated derivatives are not superior in their
discriminatory power compared with tPSA and the fPSA% value. The other molecular PSA forms and hK2 are still objects of research
and their diagnostic significance needs to be evaluated in more extensive clinical trials.
Der Urologe 05/2012; 39(4):313-323. · 0.50 Impact Factor
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ABSTRACT: Mikro-RNA (miRNA) sind nicht kodierende RNA, die grundlegende zelluläre Prozesse steuern, aber auch mit Krebsmerkmalen assoziiert
sind. Ziel dieses Artikels ist es, Grundzüge der Biogenese und Funktion von miRNA sowie ihre Bedeutung in der Tumorentwicklung,
insbesondere in der Uroonkologie zu beschreiben. Zu diesem Zweck wurde eine PubMed-Literaturrecherche durchgeführt. Bis März
2009 erschienen ca. 4500 Publikationen über miRNA. Expressionsstudien in Karzinomen und funktionelle Analysen belegen ihre
besondere Rolle in der Kanzerogenese, ihr Potenzial als diagnostische und prognostische Marker sowie als Zielstruktur für
neue Therapeutika. In der Uroonkologie wurden bisher nur wenige miRNA-Studien veröffentlicht. Tumorspezifische miRNA-Expressionen
wurden zwar für urologische Karzinome nachgewiesen, widersprüchliche Daten zeigen jedoch, dass hier die Forschung noch am
Anfang steht. Eine systematische Aufklärung charakteristischer miRNA-Anomalien könnte in Zukunft sowohl die Diagnostik als
auch die Therapie urologischer Tumoren entscheidend verbessern helfen.
MicroRNAs (miRNAs) are non-coding RNAs that regulate basic cellular processes and are associated with cancer characteristics.
The aim of this review is to summarize the principles of miRNA biogenesis and function and to describe their contribution
to tumor development, especially in uro-oncology. Therefore a PubMed search was conducted. Up to March 2009 approximately
4,500 miRNA-related articles were cited in this database. Studies of miRNA expression and functional analyses prove their
impact in carcinogenesis and their potential as diagnostic or prognostic markers or as novel therapeutic targets. Only a few
miRNA-related studies have been published in uro-oncology so far. Although tumor-specific miRNA expression has been shown
for urological neoplasms, the contradicting data show that miRNA research is still in its infancy in this field. A systematic
elucidation of characteristic miRNA abnormalities could decisively improve diagnostics as well as therapy of urological tumors.
Der Urologe 04/2012; 48(8):877-885. · 0.50 Impact Factor
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ABSTRACT: Testicular germ cell tumour (TGCT) is the most common cause of death from solid tumours in young men and especially for platinum-refractory patients novel treatment approaches are urgently needed. Using an in silico screening approach for the detection of novel cancer drugs with inhibitory effects on the tyrosine kinase activity of growth factors (e.g., VEGFR, PDGFR), we identified two compounds (HP-2 and HP-14) with antiangiogenic and antiproliferative potency, which were evaluated in endothelial cell models and TGCT cells.
HP-2 and HP-14 effectively inhibited the growth of VEGFR-2-expressing TGCT cell lines (Tera-1, Tera-2 and 2102EP) and endothelial cell models, while they failed to supress the growth of VEGFR-2-lacking tumour cells. cDNA-microarrays revealed an inhibition of the expression of several growth factor receptors and related signal transduction molecules. Vascular endothelial growth factor (VEGF)-induced cell migration was also potently inhibited. Cell cycle-regulating proteins such as p21 and p27 were upregulated, leading to an S-phase arrest. Additional in vivo evaluations confirmed the antiangiogenic potency and good tolerability of the novel substances.
Our data show that the identified novel compounds inhibit the growth of TGCT cells and decrease angiogenic microvessel formation. The mode of action involves cell cycle arresting effects and changes in the expression pattern of several angiogenic genes. The novel compounds may qualify as new candidates for targeted treatment of TGCT and merit further evaluation.
British Journal of Cancer 06/2010; 103(1):18-28. · 5.04 Impact Factor
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J Busch,
C Röllig,
L Weissbach,
C Kempkensteffen,
S Hinz,
C Jahnke,
M Schostak, M Lein,
S Weikert,
C Stephan,
S Deger,
G Ollenschläger,
K Miller,
M Schrader
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ABSTRACT: Guidelines are developed to improve the quality of patient care. The effect of German urologic guidelines has not been evaluated so far. Therefore, we aimed to systematically investigate the acceptance, use, and quality of the published guidelines from a user's perspective.
A link to an online questionnaire concerning use and barriers to the application of guidelines was distributed via e-mail by the German Society of Urology (DGU). German urologists' opinions on differences in national guideline quality were evaluated regarding prostate cancer (PCA), bladder cancer, germ cell tumors (GCT), renal cell carcinomas, and erectile dysfunction.
Four hundred sixty-seven German urologists participated. More than 90% of the participants considered guidelines to be helpful. The Internet as the main tool for guideline distribution was favored by 28.4%, followed by publication in Urologe A. The main barrier to guideline usage was attributed to the lack of up-to date clinical data. Guidelines for GCT scored best in all quality categories and reached the highest level of use (65.8%), and 40.5% of participating urologists considered the additional establishment of comprehensive care centers for GCT as more effective for quality improvement than guideline development alone. For the other urologic tumors, especially PCA, guideline development was favored as a tool for quality improvement.
More than 90% of participating urologists accept clinical guidelines as useful instruments in clinical practice and for therapeutic decisions. Our results should be integrated into guideline dissemination and implementation strategies in order to achieve a higher degree of treatment conformation to guidelines.
Der Urologe 10/2009; 49(1):75-80. · 0.50 Impact Factor
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[show abstract]
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ABSTRACT: The specificity of PSA has been enhanced by using molecular forms of PSA and free PSA (fPSA) such as percent free PSA (%fPSA), proPSA, intact PSA or BPHA and / or new serum markers. Most of these promising new serum markers like EPCA2 or ANXA3 still lack confirmation of the outstanding initial results or show only marginally enhanced specificity at high sensitivity levels. PCA3, TMPRSS2-ERG, and other analytes in urine collected after digital rectal examination with application of mild digital pressure have the potential to preferentially detect aggressive PCa and to decrease the number of unnecessary repeat biopsies. The combination of these new urinary markers with new and established serum markers seems to be most promising to further increase specificity of tPSA. Multivariate models, e. g., artificial neural networks (ANN) or logistic regression (LR) based nomograms have recently been performed by incorporating these new markers in several studies. There is generally an advantage to include the new markers and clinical data as additional parameters to PSA and %fPSA within ANN and LR models. Results of these studies and also unexpected pitfalls are discussed in this review.
Aktuelle Urologie 09/2009; 40(4):221-30. · 0.27 Impact Factor
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[show abstract]
[hide abstract]
ABSTRACT: MicroRNAs (miRNAs) are non-coding RNAs that regulate basic cellular processes and are associated with cancer characteristics. The aim of this review is to summarize the principles of miRNA biogenesis and function and to describe their contribution to tumor development, especially in uro-oncology. Therefore a PubMed search was conducted. Up to March 2009 approximately 4,500 miRNA-related articles were cited in this database. Studies of miRNA expression and functional analyses prove their impact in carcinogenesis and their potential as diagnostic or prognostic markers or as novel therapeutic targets. Only a few miRNA-related studies have been published in uro-oncology so far. Although tumor-specific miRNA expression has been shown for urological neoplasms, the contradicting data show that miRNA research is still in its infancy in this field. A systematic elucidation of characteristic miRNA abnormalities could decisively improve diagnostics as well as therapy of urological tumors.
Der Urologe 07/2009; 48(8):877-85. · 0.50 Impact Factor
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ABSTRACT: Laparoscopic surgery in urology has undergone a rapid development in the last decade. In general, many studies have underlined the benefits of laparoscopy in urology. The latest innovations in the field of minimally invasive urology are aimed at a further reduction of the morbidity associated with minimally invasive surgery. Two novel innovations are currently being developed, natural orifice transluminal endoscopic surgery (NOTES), whereby intraperitoneal access is gained through natural orifices and laparo-endoscopic single-site surgery (LESS), wherein one surgical access is used both for introducing instruments and for retrieving the specimen. Many case reports and small patient series have been published rapidly in the past two years. However, comparative randomised studies to conventional laparoscopy or open surgery do not yet exist. LESS and NOTES are two new innovative approaches, whereby feasibility studies not only for simple nephrectomy but also for complex procedures like partial nephrectomy, radical prostatectomy, ureterocystoneostomy have been published. In the next few years, comparative studies between these techniques and conventional laparoscopy can be expected.
Aktuelle Urologie 02/2009; 40(1):23-6. · 0.27 Impact Factor
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Aktuelle Urologie - AKTUEL UROL. 01/2009; 40(01):23-26.
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European Urology Supplements - EUR UROL SUPPL. 01/2009; 8(4):194-194.
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ABSTRACT: This article offers a review about the current facts of chemotherapy in testicular cancer. Besides a short presentation of the guideline-standard therapy the authors deal with the question as to why testicular cancer shows an extraordinarily high chemosensibility compared to other tumours. Furthermore, the current data on alternative chemotherapies as well as of molecular, molecular-genetic and pharmacogenetic therapeutic concepts are explored. Data were obtained from researches in Medline of the Pubmed database.
Aktuelle Urologie 12/2008; 39(6):429-35. · 0.27 Impact Factor
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ABSTRACT: Neoadjuvante und adjuvante Therapiestrategien haben in der Onkologie eine weite Verbreitung. Die Eradikation von Mikrometastasen
ist die Zielsetzung und der potentielle Gewinn, Überbehandlung und Inkaufnahme von Nebenwirkungen die Nachteile. Beim Prostatakarzinom
(PCA) wurde eine neoadjuvante und adjuvante Hormonbehandlung sowohl im Zusammenhang mit der radikalen Prostatektomie als auch
mit der Strahlentherapie in klinischen Studien untersucht. Die Ergebnisse dieser Studien legen die folgenden Therapieempfehlungen
nahe: Ein neoadjuvante Hormontherapie vor radikaler Prostatektomie ist anhand der Datenlage nicht indiziert. Eine adjuvante
Hormontherapie (LHRH-Analogon) bei Patienten mit Lymphknotenmetasen nach radikaler Prostatektomie ist gegen eine frühe PSA-progressionsgesteuerte
Therapie abzuwägen. Bei Patienten mit lokal fortgeschrittenem Tumor ist eine adjuvante Hormontherapie (Bicalutamid 150mg)
gegen eine frühe progressionsgesteuerte Therapie abzuwägen. Bei klinisch lokal fortgeschrittenen Tumoren ist vor Strahlentherapie
eine mindestens 2-monatige (maximal 6-monatige) Hormontherapie (LHRH-Analogon) bei Patienten mit geringem systemischen Risiko
(Gleason-Score <7) indiziert. Die Hormontherapie wird während der Strahlentherapie fortgeführt. Bei Patienten mit hohem systemischen
Risiko ist eine langfristige adjuvante Hormontherapie (2–3Jahre) nach Strahlentherapie indiziert.
Neoadjuvant and adjuvant therapeutic strategies are widely employed for a variety of cancer entities. The basic aim and the
potential benefit for the patient are to eradicate micrometastases, with the downside being side effects and overtreatment.
Neoadjuvant and adjuvant hormone therapy for prostate cancer have been investigated in a number of clinical studies. Based
on these studies, the following recommendations can be given: there is currently no indication for neoadjuvant therapy prior
to radical prostatectomy. Adjuvant therapy using LHRH analogs for patients with lymph node-positive tumors following radical
prostatectomy can be considered but should be weighed against early“biochemical progression triggered” treatment. For locally
advanced tumors the same is true (bicalutamide): adjuvant treatment has shown an advantage in clinically progression-free
survival; however, no systematic comparison is available with early“biochemical progression triggered” treatment. Before radiotherapy
2 months of neoadjuvant LHRH analog treatment has shown a survival advantage in patients with locally advanced tumors and
a low risk of systemic spread (Gleason <7). For high-risk patients, long-term (2–3years) adjuvant LHRH analog treatment is
indicated.
Der Urologe 10/2008; 47(11):1460-1464. · 0.50 Impact Factor
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ABSTRACT: Neoadjuvant and adjuvant therapeutic strategies are widely employed for a variety of cancer entities. The basic aim and the potential benefit for the patient are to eradicate micrometastases, with the downside being side effects and overtreatment. Neoadjuvant and adjuvant hormone therapy for prostate cancer have been investigated in a number of clinical studies. Based on these studies, the following recommendations can be given: there is currently no indication for neoadjuvant therapy prior to radical prostatectomy. Adjuvant therapy using LHRH analogs for patients with lymph node-positive tumors following radical prostatectomy can be considered but should be weighed against early"biochemical progression triggered" treatment. For locally advanced tumors the same is true (bicalutamide): adjuvant treatment has shown an advantage in clinically progression-free survival; however, no systematic comparison is available with early"biochemical progression triggered" treatment. Before radiotherapy 2 months of neoadjuvant LHRH analog treatment has shown a survival advantage in patients with locally advanced tumors and a low risk of systemic spread (Gleason <7). For high-risk patients, long-term (2-3 years) adjuvant LHRH analog treatment is indicated.
Der Urologe 10/2008; 47(11):1460-4. · 0.50 Impact Factor
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G Kristiansen,
F R Fritzsche,
K Wassermann,
C Jäger,
A Tölls, M Lein,
C Stephan,
K Jung,
C Pilarsky,
M Dietel,
H Moch
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ABSTRACT: GOLPH2 is coding the 73-kDa type II Golgi membrane antigen GOLPH2/GP73. Upregulation of GOLPH2 mRNA has been recently reported in expression array analyses of prostate cancer. As GOLPH2 protein expression in prostate tissues is currently unknown, this study aimed at a comprehensive analysis of GOLPH2 protein in benign and malignant prostate lesions. Immunohistochemically detected GOLPH2 protein expression was compared with the basal cell marker p63 and the prostate cancer marker alpha-methylacyl-CoA racemase (AMACR) in 614 radical prostatectomy specimens. GOLPH2 exhibited a perinuclear Golgi-type staining pattern and was preferentially seen in prostatic gland epithelia. Using a semiquantitative staining intensity score, GOLPH2 expression was significantly higher in prostate cancer glands compared with normal glands (P<0.001). GOLPH2 protein was upregulated in 567 of 614 tumours (92.3%) and AMACR in 583 of 614 tumours (95%) (correlation coefficient 0.113, P = 0.005). Importantly, GOLPH2 immunohistochemistry exhibited a lower level of intratumoral heterogeneity (25 vs 45%). Further, GOLPH2 upregulation was detected in 26 of 31 (84%) AMACR-negative prostate cancer cases. These data clearly suggest GOLPH2 as an additional ancillary positive marker for tissue-based diagnosis of prostate cancer.
British Journal of Cancer 09/2008; 99(6):939-48. · 5.04 Impact Factor
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ABSTRACT: Fast-track surgery describes perioperative treatment concepts ensuring a faster postoperative convalescence phase. By using a multimodal fast-track concept in patients undergoing laparoscopic radical prostatectomy, we aimed to investigate the feasibility of this procedure after elective surgery and a possible discharge 3 days postoperatively.
Twenty-five patients per group were randomized for conventional or fast-track treatment, respectively. Perioperative data, early complications, possible hospital discharge, and readmission rate were analyzed. Before hospital discharge, all patients were interviewed about their evaluation of the received regimen and their overall satisfaction perioperatively.
The mean postoperative hospital stay was 3.6 days in the fast-track group vs. 6.7 days in the conventional group (p<0.01). Overall complications were low but were significant between the two groups, with the fast-track procedure being more favorable. Readmission rate was also low but was not significant. Overall satisfaction was significantly higher in the fast-track group, whereas the subjective evaluation did not differ between the two regimens.
Fast-track concepts are well transferable in laparoscopic radical prostatectomy settings. Patients receiving this procedure, as well as clinics offering it, may benefit from a suitable fast-track concept.
Der Urologe 07/2008; 47(6):712-7. · 0.50 Impact Factor
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ABSTRACT: Hintergrund„Fast-track-Chirurgie“ beschreibt den Zusammenschluss perioperativer Behandlungsstrategien, die in einer schnelleren Rekonvaleszenz
des Patienten nach einem chirurgischem Eingriff resultieren. Ziel dieser Studie war die Evaluation der Entlassungsfähigkeit
und Komplikationsrate der Patienten nach einem neu etabliertem Fast-track-Konzept 3Tage nach einer laparoskopsich radikalen
Prostatektomie.
Patienten und MethodenIn jeweils einer Therapiegruppe wurden 25Patienten randomisiert und nach konventionellen oder Fast-track-Kriterien behandelt.
Es wurden perioperative Daten, Komplikationen, Aufenthaltsdauer und die Wiederaufnahmerate erhoben. Alle Patienten erhielten
überdies ein kurzes Interview zur persönlichen Einschätzung des erhaltenen therapeutischen Regimes und zur Feststellung der
allgemeinen perioperativen Zufriedenheit.
ErgebnisseDie mittlere postoperative Aufenthaltsdauer in der Fast-track-Gruppe betrug 3,6Tage gegenüber 6,7Tage in der konventionellen
Gruppe (p<0,01). Die Komplikationsrate in der Fast-track-Gruppe war signifikant geringer, die Wiederaufnahmerate war in beiden
Gruppen ebenfalls gering und nicht signifikant unterschiedlich. Die allgemeine perioperative Zufriedenheit der Patienten war
unter dem Fast-track-Konzept signifikant höher, die subjektiven Einschätzungen der Therapie durch die beiden Patientengruppen
unterschieden sich hingegen nicht signifikant.
SchlussfolgerungenFast-track-Verfahren sind gut auf die laparoskopisch radikale Prostatektomie übertragbar. Sowohl Patienten als auch die ausführende
Klinik können von einem funktionierendem Fast-track-Konzept im Rahmen der laparoskopisch radikalen Prostatektomie profitieren.
BackgroundFast-track surgery describes perioperative treatment concepts ensuring a faster postoperative convalescence phase. By using
a multimodal fast-track concept in patients undergoing laparoscopic radical prostatectomy, we aimed to investigate the feasibility
of this procedure after elective surgery and a possible discharge 3 days postoperatively.
Patients and methodsTwenty-five patients per group were randomized for conventional or fast-track treatment, respectively. Perioperative data,
early complications, possible hospital discharge, and readmission rate were analyzed. Before hospital discharge, all patients
were interviewed about their evaluation of the received regimen and their overall satisfaction perioperatively.
ResultsThe mean postoperative hospital stay was 3.6 days in the fast-track group vs. 6.7days in the conventional group (p<0.01).
Overall complications were low but were significant between the two groups, with the fast-track procedure being more favorable.
Readmission rate was also low but was not significant. Overall satisfaction was significantly higher in the fast-track group,
whereas the subjective evaluation did not differ between the two regimens.
ConclusionsFast-track concepts are well transferable in laparoscopic radical prostatectomy settings. Patients receiving this procedure,
as well as clinics offering it, may benefit from a suitable fast-track concept.
Der Urologe 05/2008; 47(6):712-717. · 0.50 Impact Factor
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ABSTRACT: Of visitors to the Men's Health Awareness Days (Männergesundheitstage) in different German cities, 2,200 were asked to answer a standardised questionnaire about the quality of the information presented. Fifty-one per cent of the visitors answered; of those 80% gave mainly positive feedback, especially for a walk-through prostate model and for the presentations and discussions. Visitors represented only partial groups concerning age (64 years on average), existing prostate disease (51%), and participation in examinations for early detection (cancer screening). Therefore, many of the visitors did not represent the target group (healthy and under 60 years old). Qualified urologists could make better use of consultations by informing patients about local or general information events such as these. As men are burdened with multiple health risks, future Health Days should make use of interdisciplinary schemes.
Der Urologe 03/2008; 47(2):205-11. · 0.50 Impact Factor
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[show abstract]
[hide abstract]
ABSTRACT: Es wurden 2200 Besucher der Männergesundheitstage in verschiedenen deutschen Städten darum gebeten, anhand eines einheitlichen
Fragebogens die Qualität der angebotenen Informationen zu beurteilen. Von den 51% der Besucher, die antworteten, gaben 80%
eine überwiegend positive Beurteilung ab, insbesondere zu einem begehbaren Prostatamodell sowie zu Expertenvorträgen und Diskussionen.
Die Besucher stellten in Bezug auf Alter (im Durchschnitt 64Jahre), vorhandene Prostataerkrankung (51%) und Teilnahme am
Früherkennungsprogramm ein Teilsegment dar. Daher repräsentierten viele von ihnen nicht die Zielgruppe (gesund, <60Jahre).
Der niedergelassene Urologe sollte seine Sprechstunden stärker zur Information über solche örtlichen oder allgemeinen Informationsangebote
nutzen. Da Männer mit vielfältigen Gesundheitsrisiken belastet sind, sollten „Gesundheitstage“ interdisziplinär organisiert
werden.
Of visitors to the Men’s Health Awareness Days (Männergesundheitstage) in different German cities, 2,200 were asked to answer
a standardised questionnaire about the quality of the information presented. Fifty-one per cent of the visitors answered;
of those 80% gave mainly positive feedback, especially for a walk-through prostate model and for the presentations and discussions.
Visitors represented only partial groups concerning age (64years on average), existing prostate disease (51%), and participation
in examinations for early detection (cancer screening). Therefore, many of the visitors did not represent the target group
(healthy and under 60years old). Qualified urologists could make better use of consultations by informing patients about
local or general information events such as these. As men are burdened with multiple health risks, future Health Days should
make use of interdisciplinary schemes.
Der Urologe 01/2008; 47(2):205-211. · 0.50 Impact Factor
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European Urology Supplements - EUR UROL SUPPL. 01/2008; 7(3):140-140.
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Aktuelle Urologie - AKTUEL UROL. 01/2008; 39(06):429-434.
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BJU Int. 01/2008; 102(7):902.
