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  • Bartsch, Georg  (9)
  • Health Reference Center Academic (Gale)  (9)
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  • 1
    Language: English
    In: Lasers in Surgery and Medicine, 2014, Vol.46(7), p.558(5)
    Description: To purchase or authenticate to the full-text of this article, please visit this link: http://onlinelibrary.wiley.com/doi/10.1002/lsm.22262/abstract Byline: Stefan Vallo, Katrin Eichler, Kathrin Kelly, Boris Schulz, Georg Bartsch, Axel Haferkamp, Thomas J Vogl, Stephan Zangos Purpose To evaluate the clinical value of different magnetic resonance imaging (MRI) sequences for a real-time thermo-monitoring during laser-induced thermotherapy (LITT) in kidneys. Methods Twenty-eight ex vivo pig kidneys were treated with laser ablation under MR guidance in a high-field MR scanner (Magnetom Espree or Avanto Fit, Siemens, Germany). For the thermal ablation of the kidney, a neodymium yttrium-aluminum-garnet (Nd:YAG) laser was used in combination with a special protective catheter (length 43cm, 4 French) which is sealed at the distal end. First, ablation was performed for 7, 10, and 13minutes using FLASH sequences for investigation of time-dependent growth of lesion size. In the second step, we evaluated the optimal imaging sequence during a 7minutes ablation of the kidney and after cooling using four different MR sequences (Haste, FLASH, radial VIBE, and Caipirinha DIXON). Results Macroscopic lesion volume increased from 3,784[+ or -]1,525mm.sub.3 to 7,683[+ or -]5,756mm.sub.3 after the ablation from 7 to 13minutes and MR volume ranged from 2,107[+ or -]1,674mm.sub.3 to 2,934[+ or -]1,549mm.sub.3 after the ablation from 7 to 13minutes. During ablation, FLASH (132[+ or -]34%) and radial VIBE (120[+ or -]43%) sequences displayed lesion volumes most efficiently with a trend to overestimation. The Caipirinha DIXON (323[+ or -]24%) sequence overestimated the volumes significantly during real-time monitoring. The volumes measured by MRI with FLASH (61[+ or -]30%), Haste (67[+ or -]28%), or radial VIBE (48[+ or -]14%) sequences after cooling of the kidney after ablation were always underestimated. The Caipirinha DIXON (142[+ or -]2%) sequence still overestimated the lesion volume after cooling of the kidney. Conclusion LITT is a feasible ablation modality in kidney tissue. Moreover, macroscopic and MR lesion volume increases time-dependently. For online monitoring, radial VIBE and FLASH sequences seem to be most efficient. Lasers Surg. Med. 46:558-562, 2014. [c] 2014 Wiley Periodicals, Inc. Article Note: Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.
    Keywords: Magnetic Alloys – Evaluation ; Magnetic Alloys – Comparative Analysis ; Rare Earth Metals – Evaluation ; Rare Earth Metals – Comparative Analysis ; Ablation (Surgery) – Comparative Analysis ; Rare Earth Metal Compounds – Evaluation ; Rare Earth Metal Compounds – Comparative Analysis ; Diagnostic Imaging – Comparative Analysis ; Lasers – Evaluation ; Lasers – Comparative Analysis
    ISSN: 0196-8092
    E-ISSN: 10969101
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  • 2
    Language: English
    In: BMC cancer, 07 April 2015, Vol.15, pp.224
    Description: Acquired resistance to standard chemotherapy causes treatment failure in patients with metastatic bladder cancer. Overexpression of pro-survival Bcl-2 family proteins has been associated with a poor chemotherapeutic response, suggesting that Bcl-2-targeted therapy may be a feasible strategy in patients with these tumors. The small-molecule pan-Bcl-2 inhibitor (-)-gossypol (AT-101) is known to induce apoptotic cell death, but can also induce autophagy through release of the pro-autophagic BH3 only protein Beclin-1 from Bcl-2. The potential therapeutic effects of (-)-gossypol in chemoresistant bladder cancer and the role of autophagy in this context are hitherto unknown. Cisplatin (5637(r)CDDP(1000), RT4(r)CDDP(1000)) and gemcitabine (5637(r)GEMCI(20), RT4(r)GEMCI(20)) chemoresistant sub-lines of the chemo-sensitive bladder cancer cell lines 5637 and RT4 were established for the investigation of acquired resistance mechanisms. Cell lines carrying a stable lentiviral knockdown of the core autophagy regulator ATG5 were created from chemosensitive 5637 and chemoresistant 5637(r)GEMCI(20) and 5637(r)CDDP(1000) cell lines. Cell death and autophagy were quantified by FACS analysis of propidium iodide, Annexin and Lysotracker staining, as well as LC3 translocation. Here we demonstrate that (-)-gossypol induces an apoptotic type of cell death in 5637 and RT4 cells which is partially inhibited by the pan-caspase inhibitor z-VAD. Cisplatin- and gemcitabine-resistant bladder cancer cells exhibit enhanced basal and drug-induced autophagosome formation and lysosomal activity which is accompanied by an attenuated apoptotic cell death after treatment with both (-)-gossypol and ABT-737, a Bcl-2 inhibitor which spares Mcl-1, in comparison to parental cells. Knockdown of ATG5 and inhibition of autophagy by 3-MA had no discernible effect on apoptotic cell death induced by (-)-gossypol and ABT-737 in parental 5637 cells, but evoked a significant increase in early apoptosis and overall cell death in BH3 mimetic-treated 5637(r)GEMCI(20) and 5637(r)CDDP(1000) cells. Our findings show for the first time that (-)-gossypol concomitantly triggers apoptosis and a cytoprotective type of autophagy in bladder cancer and support the notion that enhanced autophagy may underlie the chemoresistant phenotype of these tumors. Simultaneous targeting of Bcl-2 proteins and the autophagy pathway may be an efficient new strategy to overcome their "autophagy addiction" and acquired resistance to current therapy.
    Keywords: Gossypol -- Analogs & Derivatives ; Proto-Oncogene Proteins C-Bcl-2 -- Genetics ; Urinary Bladder Neoplasms -- Drug Therapy
    E-ISSN: 1471-2407
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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: Oncology Letters, 11/2017, Vol.14(5), pp.5513-5518
    Description: Treatment failure in metastatic bladder cancer is commonly caused by acquisition of resistance to chemotherapy in association with tumor progression. Since alterations of integrins can influence the adhesive and invasive behaviors of urothelial bladder cancer cell lines, the present study aimed to evaluate the role of integrins in bladder cancer cells with acquired resistance to standard first-line chemotherapy with gemcitabine, and cisplatin. Therefore, four gemcitabine- and four cisplatin-resistant sublines out of a panel of four parental urothelial bladder cancer cell lines (TCC-SUP, HT1376, T24, and 5637) were used. Expression of integrin subunits α3, α5, α6, β1, β3, and β4 was detected using flow cytometry. Adhesion and chemotaxis were analyzed. For functional assays, integrin β1 was attenuated with a blocking antibody. In untreated cells, chemotaxis was upregulated in 3/4 gemcitabine-resistant sublines. In cisplatin-resistant cells, chemotaxis was enhanced in 2/4 cell lines. Acquired chemoresistance induced the upregulation of integrin β1 in all four tested gemcitabine-resistant sublines, as well as an upregulation in 3/4 cisplatin-resistant sublines compared with parental cell lines. Following the inhibition of integrin β1, adhesion to extracellular matrix components was downregulated in 3/4 gemcitabine-resistant sublines and in all four tested cisplatin-resistant sublines. Since integrin β1 is frequently upregulated in chemoresistant urothelial cancer cell lines and inhibition of integrin β1 may influence adhesion, further studies are warranted to evaluate integrin β1 as a potential therapeutic target for bladder cancer in vivo .
    Keywords: Adhesion ; Acquired Resistance ; Cancer Cell Line Collection ; Chemotaxis ; Cisplatin ; Gemcitabine ; Integrin Β1 ; Urothelial Cancer
    ISSN: 1792-1074
    E-ISSN: 1792-1082
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  • 5
    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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  • 6
    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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  • 7
    Language: English
    In: Urologia Internationalis, July 2018, Vol.101(1), pp.16-24
    Description: Background/Aims/Objectives: To evaluate the influence of body mass index (BMI) on complications and oncological outcomes in patients undergoing radical cystectomy (RC). Methods: Clinical and histopathological parameters of patients have been prospectively collected within the “PROspective MulticEnTer RadIcal Cystectomy Series 2011”. BMI was categorized as normal weight (〈25 kg/m2), overweight (≥25–29.9 kg/m2) and obesity (≥30 kg/m2). The association between BMI and clinical and histopathological endpoints was examined. Ordinal logistic regression models were applied to assess the influence of BMI on complication rate and survival. Results: Data of 671 patients were eligible for final analysis. Of these patients, 26% (n = 175) showed obesity. No significant association of obesity on tumour stage, grade, lymph node metastasis, blood loss, type of urinary diversion and 90-day mortality rate was found. According to the ­American Society of Anesthesiologists score, local lymph node (NT) stage and operative case load patients with higher BMI had significantly higher probabilities of severe complications 30 days after RC (p = 0.037). The overall survival rate of obese patients was superior to normal weight patients (p = 0.019). Conclusions: There is no evidence of correlation between obesity and worse oncological outcomes after RC. While obesity should not be a parameter to exclude patients from cystectomy, surgical settings need to be aware of higher short-term complication risks and obese patients should be counselled ­accordingly.
    Keywords: Original Paper ; Urothelial Carcinoma ; Bladder Cancer ; Obesity ; Radical Cystectomy ; Prognosis ; Survival ; Medicine
    ISSN: 0042-1138
    E-ISSN: 1423-0399
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  • 8
    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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  • 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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