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  • 1
    Language: English
    In: Canadian Urological Association journal = Journal de l'Association des urologues du Canada, 2016, Vol.10(1-2), pp.39-44
    Description: The microblogging social media platform Twitter is increasingly being adopted in the urologic field. We aimed to analyze participants, tweet strategies, and tweet content of the Twitter discussion at a urologic conference. A comprehensive analysis of the Twitter activity at the European Association of Urology Congress 2013 (#eau2013) was performed, including characteristics of user profiles, engagement and popularity measurements, characteristics and timing of tweets, and content analysis. Of 218 Twitter contributors, doctors (45%) were the most frequent, ahead of associations (15%), companies (10%), and journals (3%). However, journals had the highest tweet/participant rate (22 tweets/participant), profile activity (median: 1177, total tweets, 1805 followers, 979 following), and profile popularity (follower/following ratio: 2.1; retweet rank percentile: 96%). Links in a profile were associated with higher engagement (p〈0.0001) and popularity (p〈0.0001). Of 1572 tweets, 57% were original tweets, 71% contained mentions, 20% contained links, and 25% included pictures. The majority of tweets (88%) were during conference hours, with an average of 24.7 tweets/hour and a peak activity of 71 tweets/hour. Overall, 59% of tweets were informative, led by the topics uro-oncology (21%), urologic research (21%), and urotechnology (12%). Limitations include the analysis of a single conference analysis, assessment of global profile and not domain-specific activity, and the rapid evolution in Twitter-using habits. Results of this single conference qualitative analysis are promising for an enrichment of the scientific discussions at urologic conferences through the use of Twitter.
    Keywords: Medicine;
    ISSN: 1911-6470
    E-ISSN: 19201214
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  • 2
    Language: English
    In: International Urology and Nephrology, 2018, Vol.50(10), pp.1821-1827
    Description: To access, purchase, authenticate, or subscribe to the full-text of this article, please visit this link: http://dx.doi.org/10.1007/s11255-018-1963-1 Byline: Christian Thomas (1), Maximilian P. Brandt (1), Stephanie Baldauf (1), Igor Tsaur (1), Sebastian Frees (1), Hendrik Borgmann (1), Wolfgang Jager (1), Georg Bartsch (1), Meike Schneider (1), Robert Dotzauer (1), Andreas Neisius (1), Axel Haferkamp (1) Keywords: Prostate cancer; Docetaxel; Rechallenge Abstract: Purpose The purpose of the study was to define clinical factors for successful treatment response and re-exposure to docetaxel in metastatic castration-resistant prostate cancer (mCRPC). Methods An mCRPC database of patients receiving first-line docetaxel and rechallenge courses was established. Several clinical factors were evaluated for prediction of treatment response. Multivariate cox-regression analysis was used to define pre-treatment and treatment factors for survival. Results Between 2005 and 2013, 94 patients with mCRPC were treated with docetaxel. Full data set and follow-up were available for 62 patients. Median follow-up was 84 m [interquartile range (IQR) 64--104 m]. Median biochemical progression-free survival (bPFS) and overall survival under docetaxel were 9 m (IQR 5--16 m) and 20 m (IQR 16--26 m), respectively. Partial PSA-response at first docetaxel-sequence (n=62), rechallenge (n=32), and third-sequence (n=22) docetaxel was 48.4%, 31.6%, and 34.8%, respectively. Time from start of primary androgen deprivation to CRPC〉47 m was the only independent pre-treatment parameter to predict improved overall survival (Hazard Ratio 0.48, p=0.015). Interestingly, there was a strong trend for improved overall survival in patients with high Gleason Score (Hazard Ratio 0.58 p=0.08). Partial PSA-response at docetaxel-rechallenge (Hazard Ratio 0.31 p=0.008) and treatment-free interval〉3 m (Hazard Ratio 3.49 p=0.014) were the only independent predictive factors under taxane treatment for overall survival. Conclusion Despite novel hormonal drugs, docetaxel still plays an important role in the treatment of mCRPC. Patients with partial-PSA-response at rechallenge or a treatment-free interval〉3 m benefit most from docetaxel re-exposure. Author Affiliation: (1) 0000 0001 1941 7111, grid.5802.f, Department of Urology, University of Mainz, Langenbeckstra[sz]e 1, 55131, Mainz, Germany Article History: Registration Date: 12/08/2018 Received Date: 10/06/2018 Accepted Date: 12/08/2018 Online Date: 17/08/2018 Article note: Christian Thomas and Maximilian P. Brandt have contributed equally to this work and shared first authorship. Andreas Neisius and Axel Haferkamp have contributed equally to this work and shared last authorship.
    Keywords: Prostate cancer ; Docetaxel ; Rechallenge
    ISSN: 0301-1623
    E-ISSN: 1573-2584
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  • 3
    Language: English
    In: Patient Preference and Adherence, 2016, Vol.10, p.2181(7)
    Description: PURPOSE: This study compares early complications after cystectomy and urinary diversion (UD) stratified by the surgical focus and case load of two different department chairpersons in a single institution in two time periods. Creating clear data about complications that can affect the quality of life is an important tool for patients to decide whether and where to perform this extensive surgery.HYPOTHESIS: A team of surgeons with a clear focus on pelvic surgery leads to lower complication rates in radical cystectomy.MATERIALS AND METHODS: Radical cystectomy was performed in two separate time periods under the patronage of two different chairmen in the same university hospital. The patient data were analyzed retrospectively and the complications 30 days after surgery were assessed using the Clavien-Dindo classification.RESULTS: Statistical analysis showed a significant difference in the severity of complications between the two time periods, A and B, in total (P〈0.001). When placing patients into subgroups, significantly more complications in period A were also seen concerning sex (male, P〈0.001; female, P=0.003), age (〈70 years, P〈0.001; 〉70 years, P≤50.001) tumor grade (low grade, P〈0.001; high grade, P≤0.001), and UD (ileal conduit, P〈0.001; neobladder, P〈0.001). In a multivariable analysis, age (P=0.031) and type of UD (P=0.028) were determined as independent predictors for complications in period A. When joining the two periods together, the type of UD (P=0.0417), age (P=0.041), and the time periods (A/B) (P〈0.001) show a significant association with the presence of complications.CONCLUSION: This study compares for the first time surgical complications in two time periods with different case load and surgical focus in one department. Categorization shows that patients should prefer radical cystectomy in centers of excellence or a high-volume hospital in order to keep complications at the lowest possible level and thus have the highest benefit for oncologic outcome and quality of life.
    Keywords: Medicine;
    ISSN: 1177-889X
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  • 4
    Language: English
    In: Patient preference and adherence, 2016, Vol.10, pp.2181-2187
    Description: This study compares early complications after cystectomy and urinary diversion (UD) stratified by the surgical focus and case load of two different department chairpersons in a single institution in two time periods. Creating clear data about complications that can affect the quality of life is an important tool for patients to decide whether and where to perform this extensive surgery. A team of surgeons with a clear focus on pelvic surgery leads to lower complication rates in radical cystectomy. Radical cystectomy was performed in two separate time periods under the patronage of two different chairmen in the same university hospital. The patient data were analyzed retrospectively and the complications 30 days after surgery were assessed using the Clavien-Dindo classification. Statistical analysis showed a significant difference in the severity of complications between the two time periods, A and B, in total (70 years, ≤0.001) tumor grade (low grade, 〈0.001; high grade, ≤0.001), and UD (ileal conduit, 〈0.001; neobladder, 〈0.001). In a multivariable analysis, age (=0.031) and type of UD (=0.028) were determined as independent predictors for complications in period A. When joining the two periods together, the type of UD (=0.0417), age (=0.041), and the time periods (A/B) (〈0.001) show a significant association with the presence of complications. This study compares for the first time surgical complications in two time periods with different case load and surgical focus in one department. Categorization shows that patients should prefer radical cystectomy in centers of excellence or a high-volume hospital in order to keep complications at the lowest possible level and thus have the highest benefit for oncologic outcome and quality of life.
    Keywords: Clavien–Dindo Classification ; Ud ; Early Complications ; High-Volume Period ; Low-Volume Period ; Radical Cystectomy ; Urinary Diversion
    ISSN: 1177-889X
    Source: MEDLINE/PubMed (U.S. National Library of Medicine)
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  • 5
    Language: English
    In: Cancer Epidemiology, February 2018, Vol.52, pp.63-69
    Description: Incidence rates for urothelial carcinoma (UC) have been reported to differ between countries within the European Union (EU). Besides occupational exposure to chemicals, other substances such as tobacco and nitrite in groundwater have been identified as risk factors for UC. We investigated if regional differences in UC incidence rates are associated with agricultural, industrial and residential land use. Newly diagnosed cases of UC between 2003 and 2010 were included. Information within 364 administrative districts of Germany from 2004 for land use factors were obtained and calculated as a proportion of the total area of the respective administrative district and as a smoothed proportion. Furthermore, information on smoking habits was included in our analysis. Kulldorff spatial clustering was used to detect different clusters. A negative binomial model was used to test the spatial association between UC incidence as a ratio of observed versus expected incidence rates, land use and smoking habits. We identified 437,847,834 person years with 171,086 cases of UC. Cluster analysis revealed areas with higher incidence of UC than others (p = 0.0002). Multivariate analysis including significant pairwise interactions showed that the environmental factors were independently associated with UC (p 〈 0.001). The RR was 1.066 (95% CI 1.052–1.080), 1.066 (95% CI 1.042–1.089) and 1.067 (95% CI 1.045–1.093) for agricultural, industrial and residential areas, respectively, and 0.996 (95% CI 0.869–0.999) for the proportion of never smokers. This study displays regional differences in incidence of UC in Germany. Additionally, results suggest that socioeconomic factors based on agricultural, industrial and residential land use may be associated with UC incidence rates.
    Keywords: Environmental Exposure ; Socioeconomic Factor ; Smoking ; Incidence Rates ; Urothelial Carcinoma ; Medicine ; Public Health
    ISSN: 1877-7821
    E-ISSN: 1877-783X
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  • 6
    Language: English
    In: International braz j urol : official journal of the Brazilian Society of Urology, 2015, Vol.41(3), pp.486-95
    Description: In patients with penile cancer (PeCa) and increased risk of inguinal lymphatic dissemination, inguinal lymphadenectomy offers a direct histological staging as the most reliable tool for assessment of the nodal metastasic status and a definitive oncologic treatment simultaneously. However, peri- and/or postoperative mutilating sequalae often occurn. We report on clinical outcome and complications of a limited inguinal lymph node (LN) dissection. Clinical and histopathological data of all patients with PeCa who underwent limited inguinal lymphadenectomy (LIL) at our institution between 1986 and 2012 were comprehensively analyzed. Perioperative results were presented in relation to one-sided procedures, if appropriate, which were assessed without cross comparison with contralateral LILs. 29 consecutive patients with PeCa aged 60±10.3 years were included in the current study with 57 one-sided LIL performed. Mean operative time for one-sided LIL was 89.0±37.3 minutes with 8.1±3.7 LNs removed. A complication rate of 54.4% (n=31), including 16 minor and 15 major complications was found in a total of 57 procedures with leg oedema being the most prevalent morbidity (15.8%). 4 patients with clinically positive LNs developed inguinal lymphatic recurrence within 9 months after surgery. Our technique of limited inguinal LN dissection provided an acceptable complication rate without aggravating morbidity. We experienced no recurrences in clinically LN negative patients, so that the approach might be a reasonable option in this scenario. In patients with enlarged LNs, radical inguinal lymphadenectomy still appears to represent the gold standard.
    Keywords: Carcinoma, Squamous Cell -- Surgery ; Lymph Node Excision -- Methods ; Penile Neoplasms -- Surgery
    E-ISSN: 1677-6119
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  • 7
    In: Vallo, Stefan and Michaelis, Martin and Gust, Kilian M and Black, Peter C and Rothweiler, Florian and Kvasnicka, Hans-Michael and Blaheta, Roman A and Brandt, Maximilian P and Wezel, Felix and Haferkamp, Axel and Cinatl, Jindrich (2016) Dasatinib enhances tumor growth in gemcitabine-resistant orthotopic bladder cancer xenografts. BMC research notes, 9 (1). p. 454.
    Description: BACKGROUND Systemic chemotherapy with gemcitabine and cisplatin is standard of care for patients with metastatic urothelial bladder cancer. However, resistance formation is common after initial response. The protein Src is known as a proto-oncogene, which is overexpressed in various human cancers. Since there are controversial reports about the role of Src in bladder cancer, we evaluated the efficacy of the Src kinase inhibitor dasatinib in the urothelial bladder cancer cell line RT112 and its gemcitabine-resistant sub-line RT112(r)GEMCI(20) in vitro and in vivo. METHODS RT112 urothelial cancer cells were adapted to growth in the presence of 20 ng/ml gemcitabine (RT112(r)GEMCI(20)) by continuous cultivation at increasing drug concentrations. Cell viability was determined by MTT assay, cell growth kinetics were determined by cell count, protein levels were measured by western blot, and cell migration was evaluated by scratch assays. In vivo tumor growth was tested in a murine orthotopic xenograft model using bioluminescent imaging. RESULTS Dasatinib exerted similar effects on Src signaling in RT112 and RT112(r)GEMCI(20) cells but RT112(r)GEMCI(20) cells were less sensitive to dasatinib-induced anti-cancer effects (half maximal inhibitory concentration (IC50) of dasatinib in RT112 cells: 349.2 ± 67.2 nM; IC50 of dasatinib in RT112(r)GEMCI(20) cells: 1081.1 ± 239.2 nM). Dasatinib inhibited migration of chemo-naive and gemcitabine-resistant cells. Most strikingly, dasatinib treatment reduced RT112 tumor growth and muscle invasion in orthotopic xenografts, while it was associated with increased size and muscle-invasive growth in RT112(r)GEMCI(20) tumors. CONCLUSION Dasatinib should be considered with care for the treatment of urothelial cancer, in particular for therapy-refractory cases.
    Keywords: RM Therapeutics. Pharmacology
    ISSN: 1756-0500
    Source: University of Kent
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  • 8
    Language: English
    In: Oncology Letters, 06/2017, Vol.13(6), pp.4085-4092
    Description: Nanoparticle albumin-bound (nab)-paclitaxel appears to exhibit better response rates in patients with metastatic urothelial cancer of the bladder whom are pretreated with nab-paclitaxel compared with conventional paclitaxel. Paclitaxel may induce multidrug resistance in patients with cancer, while the mechanisms of resistance against paclitaxel are manifold. These include reduced function of pro-apoptotic proteins, mutations of tubulin and overexpression of the drug transporter adenosine 5′-triphosphate-binding cassette transporter subfamily B, member 1 (ABCB1). To evaluate the role of ABCB1 in nab-paclitaxel resistance in urothelial cancer cells, the bladder cancer cell lines T24 and TCC-SUP, as well as sub-lines with acquired resistance against gemcitabine (T24 r GEMCI 20 and TCC-SUP r GEMCI 20 ) and vinblastine (T24 r VBL 20 and TCC-SUP r VBL 20 ) were examined. For the functional inhibition of ABCB1, multi-tyrosine kinase inhibitors with ABCB1-inhibiting properties, including cabozantinib and crizotinib, were used. Additional functional assessment was performed with cell lines stably transduced with a lentiviral vector encoding for ABCB1, and protein expression was determined by western blotting. It was indicated that cell lines overexpressing ABCB1 exhibited similar resistance profiles to nab-paclitaxel and paclitaxel. Cabozantinib and crizotinib sensitized tumor cells to nab-paclitaxel and paclitaxel in the same dose-dependent manner in cell lines overexpressing ABCB1, without altering the downstream signaling of tyrosine kinases. These results suggest that the overexpression of ABCB1 confers resistance to nab-paclitaxel in urothelial cancer cells. Additionally, small molecules may overcome resistance to anticancer drugs that are substrates of ABCB1.
    Keywords: Abcb1 ; Acquired Resistance ; Bladder Cancer ; Cabozantinib ; Cancer Cell Line Collection ; Crizotinib ; Nanoparticle Albumin-Bound Paclitaxel
    ISSN: 1792-1074
    E-ISSN: 1792-1082
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  • 9
    Language: English
    In: BMC research notes, 27 September 2016, Vol.9(1), pp.454
    Description: Systemic chemotherapy with gemcitabine and cisplatin is standard of care for patients with metastatic urothelial bladder cancer. However, resistance formation is common after initial response. The protein Src is known as a proto-oncogene, which is overexpressed in various human cancers. Since there are controversial reports about the role of Src in bladder cancer, we evaluated the efficacy of the Src kinase inhibitor dasatinib in the urothelial bladder cancer cell line RT112 and its gemcitabine-resistant sub-line RT112GEMCI in vitro and in vivo. RT112 urothelial cancer cells were adapted to growth in the presence of 20 ng/ml gemcitabine (RT112GEMCI) by continuous cultivation at increasing drug concentrations. Cell viability was determined by MTT assay, cell growth kinetics were determined by cell count, protein levels were measured by western blot, and cell migration was evaluated by scratch assays. In vivo tumor growth was tested in a murine orthotopic xenograft model using bioluminescent imaging. Dasatinib exerted similar effects on Src signaling in RT112 and RT112GEMCI cells but RT112GEMCI cells were less sensitive to dasatinib-induced anti-cancer effects (half maximal inhibitory concentration (IC) of dasatinib in RT112 cells: 349.2 ± 67.2 nM; IC of dasatinib in RT112GEMCI cells: 1081.1 ± 239.2 nM). Dasatinib inhibited migration of chemo-naive and gemcitabine-resistant cells. Most strikingly, dasatinib treatment reduced RT112 tumor growth and muscle invasion in orthotopic xenografts, while it was associated with increased size and muscle-invasive growth in RT112GEMCI tumors. Dasatinib should be considered with care for the treatment of urothelial cancer, in particular for therapy-refractory cases.
    Keywords: Acquired Resistance ; Cancer Cell Line Collection ; Dasatinib ; Gemcitabine ; Orthotopic Xenograft Model ; Urothelial Bladder Cancer
    E-ISSN: 1756-0500
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  • 10
    Language: English
    In: Minerva urologica e nefrologica = The Italian journal of urology and nephrology, June 2019, Vol.71(3), pp.205-216
    Description: Treatment strategy for inoperable and metastatic urothelial carcinoma (mUC) has been revolutionized by the introduction of programmed cell death protein 1 (PD-1) and programmed cell death protein ligand (PD-L1) antibodies. During the last 3 decades treatment options were limited to chemotherapy, making... Five antibodies including pembrolizumab (PD-L1 antibody), atezolizumab (PD-1 antibody), nivolumab (PD-1 antibody), avelumab and durvalumab (PD-L1 antibodies) have been approved in the treatment of advanced urothelial carcinoma in first- and second-line treatment setting. The objective of this review... So far pembrolizumab and atezolizumab have demonstrated overall survival (OS) benefit in phase II studies and have shown superiority over standard chemotherapy in phase III studies which has granted them approval in first and second-line treatment setting. Improved OS and durable responses were also... Pembrolizumab has to be recommended in second-line therapy due to reporting in a phase III trial and OS survival benefit compared to chemotherapy control group. In cisplatin-eligible and treatment-naïve patients with visceral or liver metastases data also slightly favors pembrolizumab rather than atezolizumab.
    Keywords: Immunotherapy -- Methods ; Urologic Neoplasms -- Immunology
    ISSN: 03932249
    E-ISSN: 1827-1758
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