M. Wirth

Synthesis and characteristics of Fe-filled multi-walled carbon nanotubes for biomedical application

Multifunctional nanocontainers can be produced based on partially filled Fe-multi walled carbon nanotubes (MWCNTs). Using thermal decomposition ferrocene filled nanotubes can be grown aligned on substrates. The encapsulated metal nanowires have diameters of 5-30 nm and a length up to few microns. They consist of single-crystalline of ? and ?-Fe- phases. Using heat treatment, it is possible to transform ?-Fe into ?-Fe. With the aid of wet chemical methods the nanotubes can be opened and additionally filled with an agent, e.g., therapeutic agents (carboplatin) or other metals (copper). Initial studies do not show a high toxicity over a period of 440 days. These materials can be used for drug delivery and hyperthermia. The specific absorption rate (SAR) is greater than 100W/(g-?-Fe) in a magnetic field of 18kA/m (f = 250kHz).

Serotonin and Melatonin Do Not Play a Prominent Role in the Growth of Prostate Cancer Cell Lines

Objectives: To investigate the effects of serotonin and melatonin (MLT) on the regulation of malignant growth and the activity of serotonin receptors (5HTR1a/-1b) in prostate cancer (PCa) cell lines. Materials and Methods: In four PCa cell lines (LNCaP, 22RV1, PC3, DU145) and two reference cell lines 5HTR1a and -1b, relative mRNA expression levels were assessed. Different serotonin and MLT receptor agonists and antagonists were used in stimulation and inhibition experiments. Results: mRNA expression of 5HTR1b was higher than that of 5HTR1a in all PCa cell lines. Serotonin showed a significant growth stimulatory effect in all PCa lines. The 5HTR1a and -1b agonists/antagonists did not significantly affect viability. MLT inhibited viability only in PC3 cells. Similarly, the 5HTR1a antagonist induced apoptotic changes in PC3 cells only at 10–4M, while the 5HTR1b antagonist induced necrosis at 10–4M in all cell lines. Cell cycle alterations were seen in PC3 and DU145 cells under the influence of the 5HTR1a antagonist. Conclusions: Serotonin receptor antagonists and agonists as well as MLT influence viability and apoptosis of PCa cell lines at supraphysiologic concentrations. In contrast to other reports, our results do not support a regulatory role of serotonin or MLT receptor activation or inhibition in PCa growth.

Implementierung der S3-Leitlinie Prostatakarzinom im klinischen Alltag

BACKGROUND Beside the quality of a guideline, the implementation in daily practice is of particular concern. The aim of this study was to determine the degree of implementation of the interdisciplinary S3 guideline on diagnostics and treatment of prostate cancer. METHODS A questionnaire containing questions regarding the implementation of the S3 guideline was sent to 119 private practice urologists and 37 urologists working in hospitals. Comparisons were made with the χ(2) test. RESULTS The response rate was 63%. Of the responding urologists, 93% reported that they used the guideline in the daily practice, while 95% considered the strong recommendations of the guideline as treatment standard. Urologists working in a hospital recommended the guideline less frequently to their patients as source of information (30 versus 58%, p = 0.0283), but more frequently to other physicians (95 versus 72%, p = 0.0294), than private practice urologists did. CONCLUSION The interdisciplinary S3 guideline on diagnostics and treatment of prostate cancer is used by the vast majority of urologists in their daily practice. The strong guideline recommendations are considered as treatment standard. A more compact presentation and a propagation of the guideline outside the urologic community might improve implementation of the guideline.

Value of lymphadenectomy for limited nodal recurrence of prostate cancer after local therapy with curative intent

After local therapy for prostate cancer, presumably isolated nodal recurrence is being detected in increasing numbers of patients by modern imaging techniques, especially by positron emission tomography (PET). The question arises whether lymphadenectomy may delay tumor progression.Conclusions concerning the value of PET/computed tomography, perioperative complications, and oncological outcome were derived from available studies and our own experiences. Six studies reported on 83 patients who underwent lymphadenectomy for suspected nodal recurrence. In cases with histological confirmation, no patient was cured.Hence, nodal recurrence in prostate cancer most likely represents a systemic affection instead of locally limited disease. If a drop in the prostate-specific antigen level occurs after lymphadenectomy, it can be assumed that the progression-free period is expected to be less than 12 months.The available data on oncological outcomes of this procedure are insufficient. Therefore, lymphadenectomy for nodal recurrence of prostate cancer remains an unproven approach.

[Implementation of the S3 prostate cancer guideline in daily clinical practice: results of a survey among urologists].

BACKGROUND Beside the quality of a guideline, the implementation in daily practice is of particular concern. The aim of this study was to determine the degree of implementation of the interdisciplinary S3 guideline on diagnostics and treatment of prostate cancer. METHODS A questionnaire containing questions regarding the implementation of the S3 guideline was sent to 119 private practice urologists and 37 urologists working in hospitals. Comparisons were made with the χ(2) test. RESULTS The response rate was 63%. Of the responding urologists, 93% reported that they used the guideline in the daily practice, while 95% considered the strong recommendations of the guideline as treatment standard. Urologists working in a hospital recommended the guideline less frequently to their patients as source of information (30 versus 58%, p = 0.0283), but more frequently to other physicians (95 versus 72%, p = 0.0294), than private practice urologists did. CONCLUSION The interdisciplinary S3 guideline on diagnostics and treatment of prostate cancer is used by the vast majority of urologists in their daily practice. The strong guideline recommendations are considered as treatment standard. A more compact presentation and a propagation of the guideline outside the urologic community might improve implementation of the guideline.

Tissue Engineering der Harnblase

ZusammenfassungIm Tissue Engineering der Harnblase mit autologer Zelltransplantation ist die hochgradige Differenzierung der in vitro auf biokompatiblen Matrizes kultivierten Zellen für die Funktionalität der Gewebekonstrukte nach der Implantation essenziell. In diesem Zusammenhang hat die terminale Differenzierung der oberflächlichen Urothelzellen (UZ) aufgrund deren Barrierefunktion gegen Urin eine entscheidende Rolle. In dieser Arbeit beschäftigen wir uns mit der Bestimmung von optimierten Konditionen für die Bildung von terminal differenziertem Urothel für die Beschichtung von größeren Flächen biologischer Membranen. Das kann uns dem Ziel der klinischen Anwendung von funktionierenden Gewebekonstrukten näher bringen.AbstractIn tissue engineering of the urinary bladder with autologous cell transplantation, high differentiation of the cells cultivated in vitro on biocompatible membranes is essential for the functionality of the tissue constructs after implantation. The terminal differentiation of superficial urothelial cells has a key role because of the barrier function of these cells against urine. The aim of this study was to determine optimized conditions for the creation of terminally differentiated urothelium to cover large membrane surfaces. This can bring us closer to the goal of using functioning tissue constructs in clinical trials.

Prostataspezifisches Antigen zur Therapiesteuerung

Today, most incident prostate cancer cases are diagnosed in early and thus potentially curable stages because of the determination of prostate-specific antigen (PSA). Treatment monitoring is another important aspect of the tumor marker PSA. In this article, contemporary recommendations for the use of PSA in treatment monitoring are discussed in the settings of active surveillance, radical prostatectomy and radiotherapy.ZusammenfassungDurch die Messung des prostataspezifischen Antigens (PSA) werden Prostatakarzinome heute überwiegend in einem frühen und somit potentiell heilbaren Stadium diagnostiziert. Eine weitere wichtige Bedeutung des Tumormarkers PSA liegt in der Therapiesteuerung. Die vorliegende Arbeit diskutiert aktuelle Empfehlungen zur PSA-Bestimmung im Therapiemonitoring bei aktiver Überwachung sowie nach radikaler Prostatektomie und Strahlentherapie.AbstractToday, most incident prostate cancer cases are diagnosed in early and thus potentially curable stages because of the determination of prostate-specific antigen (PSA). Treatment monitoring is another important aspect of the tumor marker PSA. In this article, contemporary recommendations for the use of PSA in treatment monitoring are discussed in the settings of active surveillance, radical prostatectomy and radiotherapy.

Molecular genetic markers for prostate cancer. Evidence in fine needle biopsies for improved confirmation of the diagnosis

Selected transcript markers as well as their combinations were analyzed on minimal prostate tissue specimens with regard to their diagnostic potential. Artificial prostate biopsies from RPE explants were used for evaluation and optimization of the techniques used followed by application to diagnostic prostate needle core biopsies. Minimal prostate specimens were cryopreserved and processed with standardized methods. The RNA amount of a half of each biopsy was sufficient for the analysis of 11 marker genes and one reference gene (TBP) using quantitative PCR assays.The relative transcript amounts obtained were included in several analyses including calculations for each single marker gene like median overexpression rate as well as marker combinations. Two optimized mathematical models based on relative expression levels of EZH2, hepsin, PCA3, prostein, and TRPM8 were evaluated with regard to their diagnostic potential. Compared to single marker analyses these models show higher sensitivity and specificity for prostate cancer detection.Thus biomolecular prostate cancer identification may represent a suitable diagnostic tool to supplement conventional techniques on prostate biopsies. Furthermore, an extension of this approach to PCa prognosis and the transfer to urine samples appear very promising.ZusammenfassungAusgewählte Markergene sowie deren Kombinationen wurden an verschiedenen minimalen Prostatagewebeproben hinsichtlich ihres diagnostischen Potenzials analysiert. Als Modellsystem zur Evaluierung und Optimierung dienten zunächst artifizielle Prostatabiopsien aus Präparaten von radikalen Prostatektomien (RPE). Anschließend erfolgte die Übertragung der Methoden auf Feinnadelbiopsien, welche routinemäßig zum histopathologischen Prostatakarzinomnachweis entnommen werden. Die Prostatabiopsien wurden nach standardisierten Methoden kryokonserviert und aufgearbeitet. Die RNA-Mengen, die aus je einer Biopsiehälfte gewonnen werden konnten, waren ausreichend, um 11 Markergene und ein Referenzgen (TBP) mittels quantitativer PCR bestimmen zu können.Zur Berechnung der Überexpression der Markergene in tumorhaltigen verglichen mit tumorfreien Prostatabiopsien dienten die relativen Transkriptmengen. Neben der Auswertung als Einzelmarker wurden die relativen Transkriptmengen auch in Markerkombinationen analysiert. Zwei optimierte mathematische Genmodelle auf der Basis der relativen Transkriptmengen von EZH2, Hepsin, PCA3, Prostein und TRPM8 wurden auf ihre Eignung zur Prostatakarzinomvorhersage an minimalen Gewebeproben evaluiert. Im Gegensatz zur Einzelmarkeranalyse zeigten diese Modelle eine deutlich höhere Sensitivität und Spezifität für die Prostatakarzinomvorhersage.Die hier etablierte Methodik erlaubt die Analyse prostatakarzinomassoziierter Markergene an minimalen Gewebemengen und könnte eine Ergänzung zur herkömmlichen Diagnostik von Prostatabiopsien darstellen. Die Untersuchung weiterer Markergenmodelle, auch in Hinblick auf eine Prognosevorhersage, sowie die Übertragung auf Urinproben sind Gegenstand weiterer Untersuchungen.AbstractSelected transcript markers as well as their combinations were analyzed on minimal prostate tissue specimens with regard to their diagnostic potential. Artificial prostate biopsies from RPE explants were used for evaluation and optimization of the techniques used followed by application to diagnostic prostate needle core biopsies. Minimal prostate specimens were cryopreserved and processed with standardized methods. The RNA amount of a half of each biopsy was sufficient for the analysis of 11 marker genes and one reference gene (TBP) using quantitative PCR assays.The relative transcript amounts obtained were included in several analyses including calculations for each single marker gene like median overexpression rate as well as marker combinations. Two optimized mathematical models based on relative expression levels of EZH2, hepsin, PCA3, prostein, and TRPM8 were evaluated with regard to their diagnostic potential. Compared to single marker analyses these models show higher sensitivity and specificity for prostate cancer detection.Thus biomolecular prostate cancer identification may represent a suitable diagnostic tool to supplement conventional techniques on prostate biopsies. Furthermore, an extension of this approach to PCa prognosis and the transfer to urine samples appear very promising.

Mindestmengen in der Uroonkologie

ZusammenfassungHintergrundIm Kontext komplexer chirurgischer Eingriffe können Mindestmengenregelungen die Behandlungsqualität sichern und verbessern helfen. Für einen positiven Zusammenhang zwischen hohen Fallzahlen und geringerer Morbidität oder Mortalität gibt es für verschiedene Eingriffe belastbare Evidenz. In der Uroonkologie sind diese Effekte mit moderater Stärke für die radikale Prostatektomie, die radikale Zystektomie und die radikale Nephrektomie belegt. In anderen Gesundheitssystemen wurde daher über Mindestmengenkataloge eine zunehmende Zentralisierung angestrebt.DiskussionObwohl dieses Prinzip seit 2004 auch in Deutschland für einige Leistungen Anwendung findet, existieren für die Uroonkologie bislang keine entsprechenden gesetzlichen Regelungen. Aufgrund der hohen Versorgungsrelevanz und der vorliegenden Evidenz wäre prinzipiell auch hier eine Zentralisierung ausgewählter Eingriffe denkbar.SchlussfolgerungVor Einführung einer Mindestmengenregelung in der Uroonkologie sollte jedoch zunächst die Ausgangssituation in Deutschland aufgearbeitet werden. Falls die Situation im deutschen Gesundheitswesen die Aufnahme von uroonkologischen Prozeduren in den Mindestmengenkatalog nahelegt, sollte dieser steuernde Eingriff wissenschaftlich begleitet werden. Die kontinuierliche Evaluation einer solchen Vorgabe sowie der Ergebnisqualität wären essentiell.AbstractBackgroundMinimum caseload requirements can be an appropriate tool to optimize and stabilize the quality of treatment with complex surgical procedures. For several procedures there is sufficient evidence for a positive correlation between high case numbers and lower morbidity and mortality rates. In urologic oncology there is also an effect of moderate strength for radical prostatectomy, radical cystectomy, and radical nephrectomy. Therefore, several healthcare systems have introduced minimal numbers per hospital to centralize certain procedures.DiscussionSince 2004 minimal caseload requirements have been introduced in Germany for selected operations. However, urooncologic procedures have not been included yet. Due to the high incidence of urologic malignancies and sufficient evidence, a centralization of these procedures seems to be favorable.ConclusionHowever, prior to the introduction of minimum caseload requirements for these major urooncologic procedures, exact evaluation of the available evidence for the German healthcare system will be necessary. If a minimal caseload for these procedures is introduced, the process should be monitored closely and evaluated continuously.BACKGROUND Minimum caseload requirements can be an appropriate tool to optimize and stabilize the quality of treatment with complex surgical procedures. For several procedures there is sufficient evidence for a positive correlation between high case numbers and lower morbidity and mortality rates. In urologic oncology there is also an effect of moderate strength for radical prostatectomy, radical cystectomy, and radical nephrectomy. Therefore, several healthcare systems have introduced minimal numbers per hospital to centralize certain procedures. DISCUSSION Since 2004 minimal caseload requirements have been introduced in Germany for selected operations. However, urooncologic procedures have not been included yet. Due to the high incidence of urologic malignancies and sufficient evidence, a centralization of these procedures seems to be favorable. CONCLUSION However, prior to the introduction of minimum caseload requirements for these major urooncologic procedures, exact evaluation of the available evidence for the German healthcare system will be necessary. If a minimal caseload for these procedures is introduced, the process should be monitored closely and evaluated continuously.

[Minimum caseload requirements in urologic oncology: not without evidence from health services research].

ZusammenfassungHintergrundIm Kontext komplexer chirurgischer Eingriffe können Mindestmengenregelungen die Behandlungsqualität sichern und verbessern helfen. Für einen positiven Zusammenhang zwischen hohen Fallzahlen und geringerer Morbidität oder Mortalität gibt es für verschiedene Eingriffe belastbare Evidenz. In der Uroonkologie sind diese Effekte mit moderater Stärke für die radikale Prostatektomie, die radikale Zystektomie und die radikale Nephrektomie belegt. In anderen Gesundheitssystemen wurde daher über Mindestmengenkataloge eine zunehmende Zentralisierung angestrebt.DiskussionObwohl dieses Prinzip seit 2004 auch in Deutschland für einige Leistungen Anwendung findet, existieren für die Uroonkologie bislang keine entsprechenden gesetzlichen Regelungen. Aufgrund der hohen Versorgungsrelevanz und der vorliegenden Evidenz wäre prinzipiell auch hier eine Zentralisierung ausgewählter Eingriffe denkbar.SchlussfolgerungVor Einführung einer Mindestmengenregelung in der Uroonkologie sollte jedoch zunächst die Ausgangssituation in Deutschland aufgearbeitet werden. Falls die Situation im deutschen Gesundheitswesen die Aufnahme von uroonkologischen Prozeduren in den Mindestmengenkatalog nahelegt, sollte dieser steuernde Eingriff wissenschaftlich begleitet werden. Die kontinuierliche Evaluation einer solchen Vorgabe sowie der Ergebnisqualität wären essentiell.AbstractBackgroundMinimum caseload requirements can be an appropriate tool to optimize and stabilize the quality of treatment with complex surgical procedures. For several procedures there is sufficient evidence for a positive correlation between high case numbers and lower morbidity and mortality rates. In urologic oncology there is also an effect of moderate strength for radical prostatectomy, radical cystectomy, and radical nephrectomy. Therefore, several healthcare systems have introduced minimal numbers per hospital to centralize certain procedures.DiscussionSince 2004 minimal caseload requirements have been introduced in Germany for selected operations. However, urooncologic procedures have not been included yet. Due to the high incidence of urologic malignancies and sufficient evidence, a centralization of these procedures seems to be favorable.ConclusionHowever, prior to the introduction of minimum caseload requirements for these major urooncologic procedures, exact evaluation of the available evidence for the German healthcare system will be necessary. If a minimal caseload for these procedures is introduced, the process should be monitored closely and evaluated continuously.BACKGROUND Minimum caseload requirements can be an appropriate tool to optimize and stabilize the quality of treatment with complex surgical procedures. For several procedures there is sufficient evidence for a positive correlation between high case numbers and lower morbidity and mortality rates. In urologic oncology there is also an effect of moderate strength for radical prostatectomy, radical cystectomy, and radical nephrectomy. Therefore, several healthcare systems have introduced minimal numbers per hospital to centralize certain procedures. DISCUSSION Since 2004 minimal caseload requirements have been introduced in Germany for selected operations. However, urooncologic procedures have not been included yet. Due to the high incidence of urologic malignancies and sufficient evidence, a centralization of these procedures seems to be favorable. CONCLUSION However, prior to the introduction of minimum caseload requirements for these major urooncologic procedures, exact evaluation of the available evidence for the German healthcare system will be necessary. If a minimal caseload for these procedures is introduced, the process should be monitored closely and evaluated continuously.