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  • 1
    Language: English
    In: Investigational New Drugs, 2013, Vol.31(2), pp.265-272
    Description: Pharmacologic options for patients with castration-resistant prostate cancer are limited. It has been suggested that targeting intracellular molecules, which have been altered during neoplastic development, may slow tumor growth. Therefore, the growth-blocking potential of the histone deacetylase-inhibitor LBH589 and the multiple tyrosine kinase-inhibitor TKI258, applied alone or in combination, was investigated in a panel of prostate cancer cell lines. PC-3, DU-145 or LNCaP cells were treated with various concentrations of LBH589 and/or TKI258. Tumor cell growth, cell cycle regulating proteins, HDAC3- and HDAC4-expression and histone H3 and H4 acetylation were then evaluated by MTT assay and Western blotting. LBH589 dose-dependently blocked prostate cancer cell growth. In contrast, TKI258 did not down-regulate tumor cell growth up to a 1,000 nM dosage. LBH589 elevated histone H3 and H4 acetylation. The cell cycle regulators cyclin B, cyclin D1, cdk1 and cdk4 were down-regulated in PC-3, whereas the suppressor proteins p21 and p27 were up-regulated in LNCaP by LBH589. TKI258 up-regulated p27 in PC-3 or p21 in LNCaP and additionally elevated cyclin B, cyclin D1, cdk1 and cdk4 in both cell lines. Presumably, the increase in cyclin and cdk caused by TKI258 counteracts the benefit of p21 or p27 up-regulation, resulting in TKI258 non-responsiveness. The LBH589/TKI258-combination was not superior to the LBH589 single-drug use in terms of growth reduction. Obviously, TKI258 did not enhance the sensitivity of prostate cancer cells towards an HDAC based regimen. Therefore, the LBH589/TKI258-combination probably does not provide an optimum strategy in fighting advanced prostate cancer.
    Keywords: Prostate cancer ; LBH589 ; TKI258 ; Molecular therapy ; Tumor growth
    ISSN: 0167-6997
    E-ISSN: 1573-0646
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  • 2
    In: BJU International, February 2016, Vol.117(2), pp.272-279
    Description: Byline: Atiqullah Aziz, Shahrokh F. Shariat, Florian Roghmann, Sabine Brookman-May, Christian G. Stief, Michael Rink, Felix K. Chun, Margit Fisch, Vladimir Novotny, Michael Froehner, Manfred P. Wirth, Marco J. Schnabel, Hans-Martin Fritsche, Maximilian Burger, Armin Pycha, Antonin Brisuda, Marko Babjuk, Stefan Vallo, Axel Haferkamp, Jan Roigas, Joachim Noldus, Regina Stredele, Bjorn Volkmer, Patrick J. Bastian, Evanguelos Xylinas, Matthias May Keywords: bladder cancer; radical cystectomy; mortality; nomograms; outcome Objective To externally validate the pT4a-specific risk model for cancer-specific survival (CSS) proposed by May etal. (Urol Oncol 2013; 31: 1141-1147) and to develop a new pT4a-specific nomogram predicting CSS in an international multicentre cohort of patients undergoing radical cystectomy (RC) for urothelial carcinoma of the bladder (UCB) Patients and Methods Data from 856 patients with pT4a UCB treated with RC at 21 centres in Europe and North-America were assessed. The risk model proposed by May etal., which includes female gender, presence of positive lymphovascular invasion (LVI) and lack of adjuvant chemotherapy administration as adverse predictors for CSS, was applied to our cohort. For the purpose of external validation, model discrimination was measured using the receiver-operating characteristic-derived area under the curve. A nomogram for predicting CSS in pT4a UCB after RC was developed after internal validation based on multivariable Cox proportional hazards regression analysis evaluating the impact of clinicopathological variables on CSS. Decision-curve analyses were applied to determine the net benefit derived from the two models. Results The estimated 5-year-CSS after RC was 34% in our cohort. The risk model devised by May etal. predicted individual 5-year-CSS with an accuracy of 60.1%. In multivariable Cox proportional hazards regression analysis, female gender (hazard ratio [HR] 1.45), LVI (HR 1.37), lymph node metastases (HR 2.54), positive soft tissue surgical margins (HR 1.39), neoadjuvant (HR 2.24) and lack of adjuvant chemotherapy (HR 1.67, all P 〈 0.05) were independent predictors of an adverse CSS rate and formed the features of our nomogram with a predictive accuracy of 67.1%. Decision-curve analyses showed higher net benefits for the use of the newly developed nomogram in our cohort over all thresholds. Conclusions The risk model devised by May etal. was validated with moderate discrimination and was outperformed by our newly developed pT4a-specific nomogram in the present study population. Our nomogram might be particularly suitable for postoperative patient counselling in the heterogeneous cohort of patients with pT4a UCB. Article Note: A.A. and S.F.S. contributed equally to the study.
    Keywords: Bladder Cancer ; Radical Cystectomy ; Mortality ; Nomograms ; Outcome
    ISSN: 1464-4096
    E-ISSN: 1464-410X
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  • 3
    Language: English
    In: Scandinavian Journal of Urology, 04 July 2017, Vol.51(4), pp.342-344
    Keywords: Angiomyolipoma ; Flank Pain ; Kidney ; Selective Arterial Embolization ; Ureteral Stone ; Medicine
    ISSN: 2168-1805
    E-ISSN: 2168-1813
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  • 4
    Language: English
    In: Journal of Cancer Education, 2017, Vol.32(1), pp.135-140
    Description: Many patients diagnosed with cancer search for health information on the Web. We aimed to assess the quality and reliability of online health information on prostate cancer. Google, Yahoo, and Bing were searched for the term “prostate cancer.” After selecting the most frequented websites, quality was measured by DISCERN score, JAMA benchmark criteria, and presence of HONcode certification. Popularity was assessed by Alexa tool, while accessibility, usability, and reliability were investigated by LIDA tool. Readability was analyzed by Flesch-Kincaid Reading Grade Level and Automated Readability Index. All 13 selected websites were rated as being of high quality according to the DISCERN instrument (76.5 ± 2.6 out of 80 points). JAMA benchmark criteria were fulfilled by 87 % of websites, whereas only 37 % were certified by the HONcode. Median Alexa Traffic Rank was 2718 ranging from 7 to 679,038. Websites received 2.3 ± 0.5 daily pageviews per visitor and users spent an average of 2 min 58 s ± 39 sec on the website. Accessibility (92 ± 5 %) and usability (92 ± 3 %) scores were high and reliability (88 ± 8 %) moderate according to the LIDA tool. Flesch-Kincaid Grade Level was 7.9 ± 2.2, and Automated Readability Index was 7.5 ± 2.4, rating the websites as fairly difficult to read. In conclusion, quality, accessibility, and usability of websites on prostate cancer provided a high rating in the current analysis. These findings are encouraging in view of the growing frequency of patients’ access of health information online.
    Keywords: Prostatic neoplasms ; Internet ; Consumer health information ; Health services research ; Decision making
    ISSN: 0885-8195
    E-ISSN: 1543-0154
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  • 5
    Language: English
    In: The American Journal of the Medical Sciences, June 2011, Vol.341(6), pp.478-483
    Description: The aim of the current study was to explore the clinico-oncological characteristics, and the therapeutic and survival parameters, of renal transplant recipients who developed transitional cell carcinoma (TCC) over a 30-year period at the authors’ center. Retrospective analysis of records from all registered patients who underwent kidney transplantation at the center between November 1979 and January 2010 who developed TCC of the urinary tract. From all 2001 patients analyzed during the study period, 21 recipients developed 19 TCCs of the bladder and 6 TCCs of the upper urinary tract. Among bladder TCCs, 13 (68.4%) cases were confined to mucosa (pTa or carcinoma in situ, n = 7) or submucosa (pT1, n = 6) and 6 others (31.6%) infiltrated the detrusor muscle (≥p T2); the grading distribution was 5 cases of G1, 6 of G2 and 8 of G3. All recurrent cases (n = 8) revealed local or systemic progression. The overall and tumor-specific patient survival rates were 80.2%, 54.0% and 30.0% and 84.9%, 67.4% and 58.9% for 1, 5 and 10 years, respectively. In the light of the observed increased aggressiveness of TCC in renal transplant recipients, more frequent examinations and possibly more invasive follow-up protocols should be considered for patients with 1 or more risk factors for development of TCC. Urine cytology (including ureteral wash cytology) may be used as a reliable diagnostic tool in these patients. Prophylactic contralateral nephroureterectomy might be an option in patients at high risk.
    Keywords: Kidney Transplantation ; Transitional Cell Carcinoma ; Immunosuppression ; Dialysis ; Survival ; Medicine
    ISSN: 0002-9629
    E-ISSN: 1538-2990
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  • 6
    Language: English
    In: World Journal of Urology, 2015, Vol.33(11), pp.1753-1761
    Description: To access, purchase, authenticate, or subscribe to the full-text of this article, please visit this link: http://dx.doi.org/10.1007/s00345-015-1502-y Byline: Vladimir Novotny (1), Michael Froehner (1), Matthias May (2), Chris Protzel (3), Katrin Hergenrother (3), Michael Rink (4), Felix K. Chun (4), Margit Fisch (4), Florian Roghmann (5), Rein-Juri Palisaar (5), Joachim Noldus (5), Michael Gierth (6), Hans-Martin Fritsche (6), Maximilian Burger (6), Danijel Sikic (7), Bastian Keck (7), Bernd Wullich (7), Philipp Nuhn (8), Alexander Buchner (8), Christian G. Stief (8), Stefan Vallo (9), Georg Bartsch (9), Axel Haferkamp (9), Patrick J. Bastian (10), Oliver W. Hakenberg (3), Stefan Propping (1), Atiqullah Aziz (4) Keywords: Bladder cancer; Radical cystectomy; Recurrence; Outcome Abstract: Purpose To externally validate the Christodouleas risk model incorporating pathological tumor stage, lymph node (LN) count and soft tissue surgical margin (STSM) and stratifying patients who develop locoregional recurrence (LR) after radical cystectomy (RC) for urothelial carcinoma of the bladder (UCB). In addition, we aimed to generate a new model including established clinicopathological features that were absent in the Christodouleas risk model. Methods Prospectively assessed multicenter data from 565 patients undergoing RC for UCB in 2011 qualified for final analysis. For the purpose of external validation, risk group stratification according to Christodouleas was performed. Competing-risk models were calculated to compare the cumulative incidences of LR after RC. Results After a median follow-up of 25 months (interquartile range 19--29), the LR-rate was 11.5 %. The Christodouleas model showed a predictive accuracy of 83.2 % in our cohort. In multivariable competing-risk analysis, tumor stage a[yen]pT3 (HR 4.32, p 〈 0.001), positive STSM (HR 2.93, p = 0.005), lymphovascular invasion (HR 3.41, p 〈 0.001), the number of removed LNs 〈10 (HR 2.62, p 〈 0.001) and the administration of adjuvant chemotherapy (HR 0.40, p = 0.008) independently predicted the LR-rate. The resulting risk groups revealed significant differences in LR-rates after 24 months with 4.8 % for low-risk patients, 14.7 % for intermediate-risk patients and 38.9 % for high-risk patients (p 〈 0.001 for all), with a predictive accuracy of 85.6 %, respectively. Conclusions The Christodouleas risk model has been successfully externally validated in the present prospective series. However, this analysis finds that overall model performance may be improved by incorporating lymphovascular invasion. After external validation of the newly proposed risk model, it may be used to identify patients who benefit from an adjuvant therapy and suit for inclusion in clinical trials. Author Affiliation: (1) Department of Urology, University Hospital "Carl Gustav Carus", Dresden, Germany (2) Department of Urology, St. Elisabeth Hospital, Straubing, Germany (3) Department of Urology, University Medical Center Rostock, Rostock, Germany (4) Department of Urology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany (5) Department of Urology, Marienhospital Herne, Ruhr-University Bochum, Herne, Germany (6) Department of Urology, Caritas St. Josef Medical Center, University of Regensburg, Regensburg, Germany (7) Department of Urology, University Hospital Erlangen, Erlangen, Germany (8) Department of Urology, Ludwig-Maximilians-University Munich, Munich, Germany (9) Department of Urology, Goethe-University Frankfurt, Frankfurt am Main, Germany (10) Department of Urology, Paracelsus Medical Center Golzheim, Dusseldorf, Germany Article History: Registration Date: 27/01/2015 Received Date: 02/12/2014 Accepted Date: 25/01/2015 Online Date: 08/02/2015
    Keywords: Bladder cancer ; Radical cystectomy ; Recurrence ; Outcome
    ISSN: 0724-4983
    E-ISSN: 1433-8726
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  • 7
    Language: English
    In: Annals of Surgical Oncology, 2014, Vol.21(12), pp.4034-4040
    Description: Byline: Matthias May (1), Sabine Brookman-May (2), Maximilian Burger (3), Christian Gilfrich (1), Hans-Martin Fritsche (3), Michael Rink (4), Felix Chun (4), Margit Fisch (4), Florian Roghmann (5), Joachim Noldus (5), Roman Mayr (6), Armin Pycha (6), Vladimir Novotny (7), Manfred Wirth (7), Stefan Vallo (8), Axel Haferkamp (8), Jan Roigas (9), Antonin Brisuda (10), Regina Stredele (11), Bjorn Volkmer (11), Christopher Dechet (12), Marco Schnabel (3), Stefan Denzinger (3), Christian G. Stief (2), Patrick J. Bastian (13), Atiqullah Aziz (4) Abstract: Purpose To evaluate the prognostic value of concomitant seminal vesicle invasion (cSVI) in patients with urothelial carcinoma of the bladder (UCB) and contiguous prostatic stromal infiltration in a large cystectomy series. Methods A total of 385 patients with UCB and contiguous prostatic infiltration comprised our study. Patients were divided in two groups according to cSVI. Median follow-up was 36 months (interquartile range 11--74) the primary end point was cancer-specific mortality. The prognostic impact of cSVI was evaluated using multivariable Cox regression analysis. The predictive accuracy was assessed by a receiver operating characteristic analysis. Results A total of 229 patients (59.5 %) without cSVI comprised group A, and 156 patients (40.5 %) with cSVI comprised group B. Positive lymph nodes (63 vs. 44 %, p 〈 0.001) and positive surgical margins (34 % vs. 14 %, p 〈 0.001) were more common in patients with cSVI. The 5- and 10-year cancer-specific survival rates were 41 % and 32 % (group A) and 21 and 17 % (group B) (p 〈 0.001). In multivariable analysis, pathological nodal stage (hazard ratio [HR] 2.19, p 〈 0.001), soft tissue surgical margin (HR 1.57, p = 0.010), clinical tumor stage (HR 1.46, p = 0.010), adjuvant chemotherapy (HR 0.40, p 〈 0.001), and cSVI (HR 1.69, p 〈 0.001) independently impacted cancer-specific mortality. The c-indices of the multivariable models with and without inclusion of cSVI were 0.658 (95 % confidence interval 0.60--0.71) and 0.635 (95 % confidence interval 0.58--0.69), respectively, resulting in a predictive accuracy gain of 2.3 % (p = 0.002). Conclusions In patients with UCB and prostatic stromal invasion, cSVI adversely affected cancer-specific survival compared to patients without cSVI. The inclusion of cSVI significantly improved the predictive accuracy of our multivariable model regarding survival. Author Affiliation: (1) Department of Urology, St. Elisabeth Medical Center Straubing, Straubing, Germany (2) Department of Urology, Ludwig-Maximilians-University Munich, Munich, Germany (3) Department of Urology, Caritas St. Josef Medical Center, University of Regensburg, Regensburg, Germany (4) Department of Urology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany (5) Department of Urology, Marienhospital Herne, Ruhr-University Bochum, Herne, Germany (6) Department of Urology, General Hospital of Bolzano, Bolzano, Italy (7) Department of Urology, University Hospital "Carl Gustav Carus", Dresden Technical University, Dresden, Germany (8) Department of Urology, Goethe-University Frankfurt, Frankfurt am Main, Germany (9) Department of Urology, Vivantes Medical Center Im Friedrichshain and Am Urban, Berlin, Germany (10) Department of Urology, 2nd Faculty of Medicine and Motol University Hospital, Prague, Czech Republic (11) Department of Urology, Kassel Medical Center, Kassel, Germany (12) Division of Urology, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA (13) Department of Urology, Paracelsus Medical Center Golzheim, Dusseldorf, Germany Article History: Registration Date: 17/05/2014 Received Date: 17/03/2014 Online Date: 04/06/2014 Article note: Matthias May and Sabine Brookman-May contributed equally to this article, and both should be considered first author.
    Keywords: Adjuvant Chemotherapy – Analysis ; Mortality – Analysis ; Carcinoma – Analysis;
    ISSN: 1068-9265
    E-ISSN: 1534-4681
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  • 8
    Language: English
    In: Urologic Oncology: Seminars and Original Investigations, October 2016, Vol.34(10), pp.432.e1-432.e8
    Description: To evaluate the prognostic relevance of different prostatic invasion patterns in pT4a urothelial carcinoma of the bladder (UCB) after radical cystectomy. Our study comprised a total of 358 men with pT4a UCB. Patients were divided in 2 groups—group A with stromal infiltration of the prostate via the prostatic urethra with additional muscle-invasive UCB ( = 121, 33.8%) and group B with continuous infiltration of the prostate through the entire bladder wall ( = 237, 66.2%). The effect of age, tumor grade, carcinoma in situ, lymphovascular invasion, soft tissue surgical margin, lymph node metastases, administration of adjuvant chemotherapy, and prostatic invasion patterns on cancer-specific mortality (CSM) was evaluated using competing-risk regression analysis. Decision curve analysis was used to evaluate the net benefit of including the variable invasion pattern within our model. The estimated 5-year CSM-rates for group A and B were 50.1% and 66.0%, respectively. In multivariable competing-risk analysis, lymph node metastases (hazard ratio [HR] = 1.73, 〈0.001), lymphovascular invasion (HR = 1.62, = 0.0023), soft tissue surgical margin (HR = 1.49, = 0.026), absence of adjuvant chemotherapy (HR = 2.11, 〈0.001), and tumor infiltration of the prostate by continuous infiltration of the entire bladder wall (HR = 1.37, = 0.044) were significantly associated with a higher risk for CSM. Decision curve analysis showed a net benefit of our model including the variable invasion pattern. Continuous infiltration of the prostate through the entire bladder wall showed an adverse effect on CSM. Besides including these patients into clinical trials for an adjuvant therapy, we recommend including prostatic invasion patterns in predictive models in pT4a UCB in men.
    Keywords: Bladder Cancer ; Radical Cystectomy ; Mortality ; Outcome ; Prostatic Invasion Pattern ; Medicine
    ISSN: 1078-1439
    E-ISSN: 1873-2496
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  • 9
    Language: English
    In: Clinical Genitourinary Cancer, October 2017, Vol.15(5), pp.e809-e817
    Description: This prospective multicenter study analyzed the effect of hospital and surgeon case volume on perioperative quality of care and short-term complications and mortality in 479 patients undergoing radical cystectomy for bladder cancer. We found that hospital volume might represent an at least equally important factor regarding postoperative complications as the surgeon case volume itself at European tertiary care centers. Case volume has been suggested to affect surgical outcomes in different arrays of procedures. We aimed to delineate the relationship between case volume and surgical outcomes and quality of care criteria of radical cystectomy (RC) in a prospectively collected multicenter cohort. This was a retrospective analysis of a prospectively collected European cohort of patients with bladder cancer treated with RC in 2011. We relied on 479 and 459 eligible patients with available information on hospital case volume and surgeon case volume, respectively. Hospital case volume was divided into tertiles, and surgeon volume was dichotomized according to the median annual number of surgeries performed. Binomial generalized estimating equations controlling for potential known confounders and inter-hospital clustering assessed the independent association of case volume with short-term complications and mortality, as well as the fulfillment of quality of care criteria. The high-volume threshold for hospitals was 45 RCs and, for high-volume surgeons, was 〉 15 cases annually. In adjusted analyses, high hospital volume remained an independent predictor of fewer 30-day (odds ratio, 0.34;  = .002) and 60- to 90-day (odds ratio, 0.41;  = .03) major complications but not of fulfilling quality of care criteria or mortality. No difference between surgeon volume groups was noted for complications, quality of care criteria, or mortality after adjustments. The coordination of care at high-volume hospitals might confer a similar important factor in postoperative outcomes as surgeon case volume in RC. This points to organizational elements in high-volume hospitals that enable them to react more appropriately to adverse events after surgery.
    Keywords: High Volume ; Postoperative Complications ; Quality of Health Care ; Urinary Bladder Neoplasms ; Volume-Outcome Relationship ; Medicine
    ISSN: 1558-7673
    E-ISSN: 1938-0682
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  • 10
    Language: English
    In: Emerging infectious diseases, March 2013, Vol.19(3), pp.456-9
    Description: We screened fecal specimens of 4,758 bats from Ghana and 272 bats from 4 European countries for betacoronaviruses. Viruses related to the novel human betacoronavirus EMC/2012 were detected in 46 (24.9%) of 185 Nycteris bats and 40 (14.7%) of 272 Pipistrellus bats. Their genetic relatedness indicated EMC/2012 originated from bats.
    Keywords: Africa ; Cov-Emc ; Europe ; Ghana ; Bats ; Coronavirus ; Human Betacoronavirus ; Viruses ; Chiroptera -- Virology ; Coronavirus -- Genetics ; Coronavirus Infections -- Veterinary
    ISSN: 10806040
    E-ISSN: 1080-6059
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