90 results on '"Thalmann, G. N."'
Search Results
2. Validation of the Decipher genomic classifier in patients receiving salvage radiotherapy without hormone therapy after radical prostatectomy – an ancillary study of the SAKK 09/10 randomized clinical trial
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Dal Pra, A, Ghadjar, P, Hayoz, S, Liu, V Y T, Spratt, D E, Thompson, D J S, Davicioni, E, Huang, H-C, Zhao, X, Liu, Y, Schär, C, Gut, P, Plasswilm, L, Hölscher, T, Polat, B, Hildebrandt, G, Müller, A-C, Pollack, A, Thalmann, G N, Zwahlen, D, and Aebersold, D M
- Subjects
Male ,Prostatectomy ,Salvage Therapy ,Prostatic Neoplasms ,610 Medicine & health ,Genomics ,Hematology ,Prostate-Specific Antigen ,Hormones ,Oncology ,Humans ,Neoplasm Recurrence, Local ,Retrospective Studies - Abstract
The Decipher genomic classifier (GC) has shown to independently prognosticate outcomes in prostate cancer. The objective of this study was to validate the GC in a randomized phase III trial of dose-escalated salvage radiotherapy (SRT) after radical prostatectomy.A clinical-grade whole-transcriptome assay was carried out on radical prostatectomy samples obtained from patients enrolled in Swiss Group for Clinical Cancer Research (SAKK) 09/10, a phase III trial of 350 men with biochemical recurrence after radical prostatectomy randomized to 64 Gy versus 70 Gy without concurrent hormonal therapy or pelvic nodal RT. A prespecified statistical plan was developed to assess the impact of the GC on clinical outcomes. The primary endpoint was biochemical progression; secondary endpoints were clinical progression and time to hormone therapy. Multivariable analyses adjusted for age, T-category, Gleason score, postradical prostatectomy persistent prostate-specific antigen (PSA), PSA at randomization, and randomization arm were conducted, accounting for competing risks.The analytic cohort of 226 patients was representative of the overall trial, with a median follow-up of 6.3 years (interquartile range 6.1-7.2 years). The GC (high versus low-intermediate) was independently associated with biochemical progression [subdistribution hazard ratio (sHR) 2.26, 95% confidence interval (CI) 1.42-3.60; P0.001], clinical progression (HR 2.29, 95% CI 1.32-3.98; P = 0.003), and use of hormone therapy (sHR 2.99, 95% CI 1.55-5.76; P = 0.001). GC high patients had a 5-year freedom from biochemical progression of 45% versus 71% for GC low-intermediate. Dose escalation did not benefit the overall cohort, nor patients with lower versus higher GC scores.This study represents the first contemporary randomized controlled trial in patients treated with early SRT without concurrent hormone therapy or pelvic nodal RT that has validated the prognostic utility of the GC. Independent of standard clinicopathologic variables and RT dose, high-GC patients were more than twice as likely than lower-GC patients to experience biochemical and clinical progression and receive of salvage hormone therapy. These data confirm the clinical value of Decipher GC to personalize the use of concurrent systemic therapy in the postoperative salvage setting.
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- 2022
3. Therapiemanagement des stumpfen Hodentraumas
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Lyttwin, B., Moltzahn, F., and Thalmann, G. N.
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- 2017
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4. MUC1 is upregulated in advanced prostate cancer and is an independent prognostic factor
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Genitsch, V, Zlobec, I, Thalmann, G N, and Fleischmann, A
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- 2016
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5. Morphological and molecular characteristics of HER2 amplified urothelial bladder cancer
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Tschui, J., Vassella, E., Bandi, N., Baumgartner, U., Genitsch, V., Rotzer, D., Seiler, R., Thalmann, G. N., and Fleischmann, A.
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- 2015
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6. Impact of perioperative chemotherapy on survival in patients with advanced primary urethral cancer: results of the international collaboration on primary urethral carcinoma
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Gakis, G., Morgan, T. M., Daneshmand, S., Keegan, K. A., Todenhöfer, T., Mischinger, J., Schubert, T., Zaid, H. B., Hrbacek, J., Ali-El-Dein, B., Clayman, R. H., Galland, S., Olugbade, K., Rink, M., Fritsche, H.-M., Burger, M., Chang, S. S., Babjuk, M., Thalmann, G. N., Stenzl, A., and Efstathiou, J. A.
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- 2015
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7. Long-term outcome of patients with clinical stage I high-risk nonseminomatous germ-cell tumors 15 years after one adjuvant cycle of bleomycin, etoposide, and cisplatin chemotherapy
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Vidal, A. D., Thalmann, G. N., Karamitopoulou-Diamantis, E., Fey, M. F., and Studer, U. E.
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- 2015
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8. Immunohistochemical determination of p53 overexpression: An easy and readily available method to identify progression in superficial bladder cancer?
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Burkhard, F. C., Markwalder, R., Thalmann, G. N., and Studer, U. E.
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- 1997
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9. Prognostic factors in lymph node metastases of prostatic cancer patients: the size of the metastases but not extranodal extension independently predicts survival
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Fleischmann, A, Schobinger, S, Markwalder, R, Schumacher, M, Burkhard, F, Thalmann, G N, and Studer, U E
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- 2008
10. Can the reverse transcriptase-polymerase chain reaction for prostate specific antigen and prostate specific membrane antigen improve staging and predict biochemical recurrence?
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ADSAN, Ö., CECCHINI, M. G., BISOFFI, M., WETTERWALD, A., KLIMA, I., DANUSER, H.-J., STUDER, U. E., and THALMANN, G. N.
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- 2002
11. Extragonadal retroperitoneal germ cell tumor: evidence of origin in the testis
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Scholz, M., Zehender, M., Thalmann, G. N., Borner, M., Thöni, H., and Studer, U. E.
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- 2002
12. La dénervation rénale unilatérale et le système kallikréine-bradykinine rénal chez le rat
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Thalmann, G. N., Birkhäuser, F., Imboden, H., Bohlender, J., Nussberger, J., and Amstutz, C.
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570 Life sciences ,biology ,610 Medicine & health - Abstract
But de l’étude L’effet antihypertenseur de la dénervation rénale chez les patients hypertendus s’explique partiellement par une augmentation de la natriurèse tubulaire. Pour étudier une contribution possible du système kallikréine-kinines (SKK) à cette natriurèse dans le rat, nous avons dosé dans le plasma et dans les tissus l’activité de la kallikréine (AK) et la concentration de la bradykinine (BK). Méthodes Pour AK, nous avons adapté et validé un essai enzymatique qui libère la para-nitroaniline à partir du tripeptide H-D-Pro-Phe-Arg-pNA ; les coefficients de variation (CV) intra-essai et inter-essai étaient inférieurs à 8 % pour AK plasmatique et tissulaire (plasma n = 6 et 13, tissu n = 4). La linéarité d’une série de dilutions confirmait la spécificité de l’essai. Le dosage de BK tissulaire se basait sur une méthode établie pour le plasma : tissus étaient homogénéisés et BK extraite et isolée par éthanol et HPLC, et finalement quantifiée par radio-immunoessai. Les CV intra- et inter-essai pour BK étaient 18 % dans le plasma (n = 8 et n = 35) et inférieurs à 16 % dans différents tissus (n = 5–8). Résultats Chez le rat mâle Wistar (n = 3), la BK plasmatique était de 8,2 ± 6,6 fmol/mL (M ± SD) et la BK tissulaire (fmol/g) variait, pour les 14 organes testés, de 14 ± 3 pour le cerveau à 521 ± 315 pour la glande sous-maxillaire. Six jours après dénervation rénale gauche, la BK rénale gauche (89 ± 9) n’était pas différente comparée à la BK rénale droite (75 ± 23). De même, l’AK était identique dans les deux reins (gauche 18,0 ± 1,5, droit 15,8 ± 1,4 μkat/g). Conclusion Un effet éventuel de la dénervation rénale unilatéral sur le SKK rénal devrait donc être bilatéral., Aim The antihypertensive effect of renal denervation in hypertensive patients is partially explained by increased tubular natriuresis. To study the possible contribution of the kallikrein-kinin system (KKS) to this natriuretic effect in rats, we measured kallikrein activity (KA) and bradykinin concentrations (BK) in plasma and tissues. Methods To measure KA, we adapted and validated an enzymatic assay that cleaves para-nitroaniline (pNA) from the tripeptide H-D-Pro-Phe-Arg-pNA. The coefficients of variation (CV) within- and between-assays were less than 8% for plasma and tissue KA (plasma n = 6 and 13; tissue n = 4). Linear results for serially diluted samples confirmed the assay specificity. Tissue BK determinations were based on an established assay for plasma BK: tissue was homogenized and kinins extracted in ethanol, and BK was isolated by high-performance (HPLC) liquid chromatography and quantitated by radioimmunassay. Within- and between-assay CV for plasma BK were 18% (n = 8 and n = 35, respectively) and for BK in various tissues less than 16% (n = 5-8). Results In male Wistar rats (n = 3), plasma BK was 8.2 ± 6.6 fmol/mL (mean ± SD), and tissue BK (fmol/g) in 14 tested organs varied between brain (14 ± 3) and submaxillary gland (521 ± 315). Six days after left-sided unilateral renal denervation, left renal tissue BK (89 ± 9) was not different from right renal BK (75 ± 23). Similarly, KA was comparable in the two kidneys (left 18.0 ± 1.5, right 15.8 ± 1.4 μkat/g). Conclusion Any possible effect of unilateral renal denervation on the kidney's KKS would have to be bilateral.
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- 2013
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13. [Bone metastasis in prostate cancer]
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Moltzahn, F and Thalmann, G N
- Abstract
Bone metastasis and skeletal complications have a devastating impact on the quality of life and are a major cause of morbidity in prostate cancer patients. In addition to established bone-targeted therapies, new drugs such as endothelin A receptor antagonists, MET and VEGFR-2 antagonists or radiopharmaceuticals are in the focus of development. The standard care in prostate cancer patients with bone metastases to prevent skeletal-related events (SRE) are bisphosphonates. Denosumab, a human monoclonal antibody against RANKL, appeared to be superior to zoledronic acid for prevention of SRE and has been shown to prolong bone metastases-free survival. In contrast to zoledronic acid, denosumab clearance is not dependent on kidney function and can be administered subcutaneously. Similar rates of toxicity were observed for both substances; however, long-term data for denosumab are limited.
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- 2012
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14. [Lymphadenectomy for bladder cancer: current status and controversies]
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Metzger, T, Thalmann, G N, and Zehnder, P
- Abstract
Pelvic lymph node dissection is an integral part of the radical cystectomy procedure for patients with muscle-invasive bladder cancer. The optimal extent of the lymphadenectomy (LND) and mainly the proximal template boundary remain controversial issues. In view of the existing mapping studies and retrospective analyses, extended LND up to the mid-upper third of the common iliac vessels appears to provide further prognostic and therapeutic benefit and therefore should be defined as standard LND. This applies for all procedures irrespective of the choice of surgical approach (open surgery, minimally invasive approach). In this context total lymph node count is not a quality criterion because nodal yield is overly influenced by the individual patient's anatomy, surgical technique, template applied and pathological work-up. Consecutively, considerable inter-institutional differences result, which render any comparison impossible. Lymph node density is thought to be a superior prognostic factor, but it is similarly influenced by the above-mentioned factors. Concerning molecular techniques to improve the sensitivity of postoperative nodal staging further research is necessary. The two ongoing prospective randomized trials will potentially help to further define the optimal LND template.
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- 2012
15. Antegrade perfusion with bacillus Calmette-Guérin in patients with non-muscle-invasive urothelial carcinoma of the upper urinary tract: who may benefit?
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Giannarini, G, Kessler, T M, Birkhäuser, F D, Thalmann, G N, Studer, U E, University of Zurich, and Studer, U E
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2748 Urology ,610 Medicine & health ,10046 Balgrist University Hospital, Swiss Spinal Cord Injury Center - Published
- 2011
16. Nuclear iASPP may facilitate prostate cancer progression
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Morris, E V, primary, Cerundolo, L, additional, Lu, M, additional, Verrill, C, additional, Fritzsche, F, additional, White, M J, additional, Thalmann, G N, additional, ten Donkelaar, C S, additional, Ratnayaka, I, additional, Salter, V, additional, Hamdy, F C, additional, Lu, X, additional, and Bryant, R J, additional
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- 2014
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17. The prognostic value of cytology and fluorescence in situ hybridization in the follow-up of nonmuscle-invasive bladder cancer after intravesical Bacillus Calmette-Guérin therapy
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Savic, S, Zlobec, I, Thalmann, G N, Engeler, D, Schmauss, M, Lehmann, K, Mattarelli, G, Eichenberger, T, Dalquen, P, Spieler, P, Schoenegg, R, Gasser, T C, Sulser, T, Forster, T, Zellweger, T, Casella, R, Bubendorf, L, University of Zurich, and Bubendorf, L
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10062 Urological Clinic ,Cancer Research ,Oncology ,610 Medicine & health ,2730 Oncology ,1306 Cancer Research - Published
- 2009
18. Immunohistochemical determination of p53 overexpression
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Burkhard, F. C., Markwalder, R., Thalmann, G. N., and Studer, U. E.
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610 Medicine & health - Published
- 1997
19. Everolimus as first-line therapy in nonrapidly progressive metastatic castration-resistant prostate cancer (mCRPC): A multicenter phase II trial (SAKK 08/08).
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Templeton, A., primary, Rothermundt, C., additional, Cathomas, R., additional, Baertschi, D., additional, Droege, C., additional, Gautschi, O., additional, Borner, M. M., additional, Fechter, E., additional, Stenner, F., additional, Winterhalder, R. C., additional, Mueller, B., additional, Dutoit, V., additional, Dietrich, P., additional, Schiess, R., additional, Wild, P., additional, Thalmann, G. N., additional, Klingbiel, D., additional, and Gillessen, S., additional
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- 2011
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20. Gold-nanoparticles for optoacoustic imaging and therapy.
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Frenz, M., primary, Kitz, M., additional, Preisser, S., additional, Jaeger, M., additional, Wetterwald, A., additional, and Thalmann, G. N., additional
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- 2011
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21. Vapor bubble generation around gold nano-particles and its application to damaging of cells
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Kitz, M., primary, Preisser, S., additional, Wetterwald, A., additional, Jaeger, M., additional, Thalmann, G. N., additional, and Frenz, M., additional
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- 2011
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22. Comparison of HER2 amplification in primary tumors and lymph node metastases of urinary bladder cancer.
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Fleischmann, A., primary, Seiler, R., additional, Rotzer, D., additional, and Thalmann, G. N., additional
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- 2010
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23. Pelvic lymph nodes: distribution and nodal tumour burden of urothelial bladder cancer
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Seiler, R., primary, von Gunten, M., additional, Thalmann, G. N., additional, and Fleischmann, A., additional
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- 2010
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24. RE: PELVIC LYMPH NODE METASTASES FROM BLADDER CANCER: OUTCOME IN 83 PATIENTS AFTER RADICAL CYSTECTOMY AND PELVIC LYMPHADENECTOMY
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Mills, R. D., primary, Turner, W. H., additional, Fleischmann, A., additional, Markwalder, R., additional, Thalmann, G. N., additional, and Studer, U. E., additional
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- 2002
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25. RE: PELVIC LYMPH NODE METASTASES FROM BLADDER CANCER: OUTCOME IN 83 PATIENTS AFTER RADICAL CYSTECTOMY AND PELVIC LYMPHADENECTOMY
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Neulander, Endre Z., primary, Mills, R. D., additional, Turner, W. H., additional, Fleischmann, A., additional, Markwalder, R., additional, Thalmann, G. N., additional, and Studer, U. E., additional
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- 2002
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26. PELVIC LYMPH NODE METASTASES FROM BLADDER CANCER: OUTCOME IN 83 PATIENTS AFTER RADICAL CYSTECTOMY AND PELVIC LYMPHADENECTOMY
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MILLS, R. D., primary, TURNER, W. H., additional, FLEISCHMANN, A., additional, MARKWALDER, R., additional, THALMANN, G. N., additional, and STUDER, U. E., additional
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- 2001
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27. Suramin-Induced Decrease in Prostate-Specific Antigen Expression With No Effect on Tumor Growth in the LNCaP Model of Human Prostate Cancer
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Thalmann, G. N., primary, Sikes, R. A., additional, Chang, S.-M., additional, Johnston, D. A., additional, von Eschenbach, A. C., additional, and Chung, L. W. K., additional
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- 1996
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28. Lymphadenektomie im Rahmen der radikalen Zystektomie : Aktueller Stand und Kontroversen.
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Metzger T, Thalmann GN, Zehnder P, Metzger, T, Thalmann, G N, and Zehnder, P
- Abstract
Pelvic lymph node dissection is an integral part of the radical cystectomy procedure for patients with muscle-invasive bladder cancer. The optimal extent of the lymphadenectomy (LND) and mainly the proximal template boundary remain controversial issues. In view of the existing mapping studies and retrospective analyses, extended LND up to the mid-upper third of the common iliac vessels appears to provide further prognostic and therapeutic benefit and therefore should be defined as standard LND. This applies for all procedures irrespective of the choice of surgical approach (open surgery, minimally invasive approach). In this context total lymph node count is not a quality criterion because nodal yield is overly influenced by the individual patient's anatomy, surgical technique, template applied and pathological work-up. Consecutively, considerable inter-institutional differences result, which render any comparison impossible. Lymph node density is thought to be a superior prognostic factor, but it is similarly influenced by the above-mentioned factors. Concerning molecular techniques to improve the sensitivity of postoperative nodal staging further research is necessary. The two ongoing prospective randomized trials will potentially help to further define the optimal LND template. [ABSTRACT FROM AUTHOR]
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- 2012
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29. Ileum-Neoblase nach Studer.
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Burkhard, F. C., Thalmann, G. N., Studer, U. E., Schumacher, M., Danuser, H. J., and Zingg, E. J.
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- 2010
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30. Erste Erfahrungen mit der intravesikalen Instillation von Oxybutyninhydrochlorid bei Patienten mit Detrusorhyperreflexie.
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Danuser, H., Springer, J. P., Thalmann, G. N., and Studer, U. E.
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- 1996
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31. Can cancer cells transform normal host cells into malignant cells?
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Pathak, S, Nemeth, MA, Multani, AS, Thalmann, GN, von Eschenbach, AC, Chung, LWK, Nemeth, M A, Multani, A S, Thalmann, G N, von Eschenbach, A C, and Chung, L W
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- 1997
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32. Genetic changes associated with the acquisition of androgen-independent growth, tumorigenicity and metastatic potential in a prostate cancer model.
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Hyytinen, E-R, Thalmann, GN, Zhau, HE, Karhu, R, Kallioniemi, O-P, Chung, LWK, Visakorpi, T, Thalmann, G N, Zhau, H E, and Chung, L W
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- 1997
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33. Characterisation of bladder cancer drug responses in organoids and ex vivo models
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Kiener, M., Karkampouna, S., Thalmann, G. N., Seiler, R., and Kruithof-De Julio, M.
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610 Medicine & health - Full Text
- View/download PDF
34. Corrigendum to ‘EAU-ESMO Consensus Statements on the Management of Advanced and Variant Bladder Cancer—An International Collaborative Multistakeholder Effort Under the Auspices of the EAU-ESMO Guidelines Committees’ [European Urology 77 (2020) 223–250](S0302283819307638)(10.1016/j.eururo.2019.09.035)
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Bogdan Geavlete, Stefano Fanti, Susanne Krege, Alberto Briganti, Harry W. Herr, Shaista Hafeez, Mark Frydenberg, Marek Babjuk, Willem de Blok, Antti Salminen, Maria De Santis, Yann Neuzillet, Arnulf Stenzl, Joost L. Boormans, Hein Van Poppel, Karel Decaestecker, Vibeke Løgager, Jorg R. Oddens, Silke Gillessen, Pedro C. Lara, Berardino De Bari, Baris Turkbey, Andrew K. Williams, Thomas Wiegel, Mihai Dorin Vartolomei, Robert Jones, Riccardo Valdagni, Vincent Khoo, Ashish M. Kamat, Christoph R. Müller, Georgios Gakis, Neeraj Agarwal, Annemarie Leliveld, Franklin A. Vives Rivera, Robert Jan Smeenk, Luís Pacheco-Figueiredo, H. Maxim Bruins, Juan Palou, Jorge Huguet, Konstantinos Dimitropoulos, Jonathan E. Rosenberg, Carl Salembier, Ken Herrmann, Iris Brummelhuis, Morgan Rouprêt, Helle Pappot, Susanne Osanto, Shahrokh F. Shariat, Anita Smits, Susanne Vahr Lauridsen, Manish I. Patel, Theo H. van der Kwast, Paul Sargos, Michel Bolla, Karin Plass, Jurgen J. Fütterer, Hugh Mostafid, Olivier Rouvière, Valérie Fonteyne, Erik Veskimäe, Bradley R. Pieters, Richard P. Meijer, Anne E. Kiltie, Tom J.H. Arends, Arndt Hartmann, Amir Sherif, Antoni Vilaseca, Stéphane Culine, Wim J.G. Oyen, Evanguelos Xylinas, Daniel Castellano, Shomik Sengupta, James N'Dow, Maria J. Ribal, Mesut Remzi, Richard Zigeuner, A. Müller, Richard Cathomas, Joaquim Bellmunt, Nicholas D. James, Paolo Gontero, Pieter De Visschere, Eva Compérat, Alison Birtle, Margitta Retz, Dickon Hayne, Michael Rink, Virginia Hernández, J. Alfred Witjes, Marco Moschini, J. Domínguez-Escrig, Yohann Loriot, Estefania Linares-Espinós, Peter C. Black, Alberto Bossi, Bertrand Tombal, Sylvain Ladoire, Aristotle Bamias, Ananya Choudhury, Simon J. Crabb, Steven MacLennan, Peter Wiklund, Antoine G. van der Heijden, Arturo Chiti, Bernhard Grubmüller, Barbara Alicja Jereczek-Fossa, Alan Horwich, George N. Thalmann, Bernard H. Bochner, Florian Roghmann, Max Bürger, Jan Oldenburg, Peter Hoskin, Andrea Necchi, Jonathan Richenberg, Anja Lorch, Peter Paul M. Willemse, Donna E. Hansel, M. Carmen Mir, Thomas Powles, Theo M. de Reijke, Ann Henry, Witjes, J. A., Babjuk, M., Bellmunt, J., Bruins, H. M., De Reijke, T. M., De Santis, M., Gillessen, S., James, N., Maclennan, S., Palou, J., Powles, T., Ribal, M. J., Shariat, S. F., Van Der Kwast, T., Xylinas, E., Agarwal, N., Arends, T., Bamias, A., Birtle, A., Black, P. C., Bochner, B. H., Bolla, M., Boormans, J. L., Bossi, A., Briganti, A., Brummelhuis, I., Burger, M., Castellano, D., Cathomas, R., Chiti, A., Choudhury, A., Comperat, E., Crabb, S., Culine, S., De Bari, B., De Blok, W., De Visschere, P. J. L., Decaestecker, K., Dimitropoulos, K., Dominguez-Escrig, J. L., Fanti, S., Fonteyne, V., Frydenberg, M., Futterer, J. J., Gakis, G., Geavlete, B., Gontero, P., Grubmuller, B., Hafeez, S., Hansel, D. E., Hartmann, A., Hayne, D., Henry, A. M., Hernandez, V., Herr, H., Herrmann, K., Hoskin, P., Huguet, J., Jereczek-Fossa, B. A., Jones, R., Kamat, A. M., Khoo, V., Kiltie, A. E., Krege, S., Ladoire, S., Lara, P. C., Leliveld, A., Linares-Espinos, E., Logager, V., Lorch, A., Loriot, Y., Meijer, R., Mir, M. C., Moschini, M., Mostafid, H., Muller, A. -C., Muller, C. R., N'Dow, J., Necchi, A., Neuzillet, Y., Oddens, J. R., Oldenburg, J., Osanto, S., Oyen, W. J. G., Pacheco-Figueiredo, L., Pappot, H., Patel, M. I., Pieters, B. R., Plass, K., Remzi, M., Retz, M., Richenberg, J., Rink, M., Roghmann, F., Rosenberg, J. E., Roupret, M., Rouviere, O., Salembier, C., Salminen, A., Sargos, P., Sengupta, S., Sherif, A., Smeenk, R. J., Smits, A., Stenzl, A., Thalmann, G. N., Tombal, B., Turkbey, B., Lauridsen, S. V., Valdagni, R., Van Der Heijden, A. G., Van Poppel, H., Vartolomei, M. D., Veskimae, E., Vilaseca, A., Rivera, F. A. V., Wiegel, T., Wiklund, P., Willemse, P. -P. M., Williams, A., Zigeuner, R., Horwich, A., Urology, APH - Personalized Medicine, APH - Quality of Care, CCA - Cancer Treatment and Quality of Life, Radiotherapy, UCL - SSS/IREC/CHEX - Pôle de chirgurgie expérimentale et transplantation, and UCL - (SLuc) Service d'urologie
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medicine.medical_specialty ,Bladder cancer ,business.industry ,Urology ,030232 urology & nephrology ,MEDLINE ,Cancer ,Regret ,medicine.disease ,3. Good health ,03 medical and health sciences ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Medicine ,Urologia ,University medical ,Bufeta -- Càncer ,Protocols clínics ,business - Abstract
The authors regret that a co-author was mistakenly missed from the authorship. The following co-author should have been included in the authorship: Peter-Paul M. Willemse Department of Oncological Urology, University Medical Center, Utrecht Cancer Center, Utrecht, The Netherlands
- Published
- 2020
35. A Systematic Review of the Role of Definitive Local Treatment in Patients with Clinically Lymph Node-positive Prostate Cancer
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Mack Roach, Alberto Briganti, Firas Abdollah, Thomas Seisen, Eugenio Ventimiglia, Valérie Fonteyne, Karim Touijer, George N. Thalmann, Nicholas D. James, Liang Cheng, Ronald C. Chen, Ventimiglia, E., Seisen, T., Abdollah, F., Briganti, A., Fonteyne, V., James, N., Roach, M., Thalmann, G. N., Touijer, K., Chen, R. C., and Cheng, L.
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Oncology ,Male ,medicine.medical_specialty ,Urology ,medicine.medical_treatment ,030232 urology & nephrology ,MEDLINE ,Context (language use) ,Pelvis ,03 medical and health sciences ,Prostate cancer ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Prostatectomy ,Radiotherapy ,business.industry ,Local treatment ,Prostatic Neoplasms ,Retrospective cohort study ,Androgen Antagonists ,Evidence-based medicine ,medicine.disease ,Combined Modality Therapy ,Survival Analysis ,Radiation therapy ,Systematic review ,030220 oncology & carcinogenesis ,Lymphatic Metastasis ,Surgery ,Lymph Nodes ,business - Abstract
Context: There is uncertainty regarding the oncologic effectiveness and the survival advantage of local treatment (LT) in men with clinically lymph node-positive (cN+) prostate cancer (PCa). Objective: To systematically review the current literature comparing oncologic outcomes associated with the use of any form of LT for PCa patients with cN+ disease. Evidence acquisition: A computerized bibliographic search of the Medline, Embase, and Cochrane databases was performed for all studies reporting comparative oncologic outcomes of LT ± androgen deprivation therapy (ADT) versus ADT alone. LT included both radical prostatectomy (RP) and radiotherapy (RT). Using the methodology recommended by the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines, we identified five nonrandomized comparative retrospective studies published between 1999 and 2018, which were eligible for inclusion in this systematic review. A narrative review and risk-of-bias assessment were performed to determine the impact of LT on recurrence-free survival, cancer-specific survival (CSS), and overall survival (OS). Evidence synthesis: Four studies compared the use of RT ± ADT versus ADT alone, whereas one study compared any form of LT ± ADT versus ADT alone. Different statistical strategies were used in the included studies to account for baseline measured and unmeasured confounders. Overall, the use of RT and, generally speaking, any form of LT was associated with an OS as well as a CSS benefit over ADT alone, without any clear superiority shown either by RP ± ADT or by RT ± ADT. Conclusions: Our systematic review suggests an advantage in terms of both OS and CSS for men with cN+ PCa receiving LT. However, these results should be interpreted with caution due to the low level of evidence of available reports. Patient summary: We reviewed the studies that assessed the role of local treatment in men with prostate cancer and with clinical evidence of lymph node involvement at diagnosis. We found that local treatment was constantly associated with recurrence-free, cancer-specific, and overall survival benefits throughout the included studies. Local treatment for clinically lymph node-positive prostate cancer is constantly associated with recurrence-free, cancer-specific, and overall survival benefits throughout the studies included in this systematic review.
- Published
- 2019
36. A 2-center review of histopathology of variants of upper urinary tract urothelial carcinoma and their impact on clinical outcomes.
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Giudici N, Schoch A, Genitsch V, Rodriguez-Calero A, Thalmann GN, and Seiler R
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- Humans, Male, Female, Aged, Middle Aged, Aged, 80 and over, Retrospective Studies, Urologic Neoplasms pathology, Urologic Neoplasms surgery, Ureteral Neoplasms pathology, Ureteral Neoplasms surgery, Carcinoma, Transitional Cell pathology, Carcinoma, Transitional Cell surgery
- Abstract
Introduction: Similar to bladder cancer, about one third of upper tract urothelial carcinoma (UTUC) present variant histology (VH). We aim to evaluate the incidence, clinical characteristics and the impact on outcomes of VH in UTUC., Methods: We consecutively enrolled 77 patients treated between 2009 and 2022 by radical surgery for UTUC from a secondary and a tertiary referral center. A pathology review of all specimens was performed by 1 independent uropathologist for each center. We compared pure UTUC and UTUC with VH and the accuracy of endoscopic biopsy. Descriptive and comparative analysis was performed to assess the association with clinical characteristics and the Kaplan-Meier estimator to compare outcomes., Results: Median follow-up after surgery was 51 months. VH was present in 21/77 (28%) patients and 4/21 (19%) patients had multiple variants. The most frequent VH was squamous 12/21 (57%), followed by glandular 7/21 (33%) and micropapillary 3/21 variants (14%). Neuroendocrine carcinoma was present in 2 patients. Nested variant was found in 1 patient. Muscle invasive tumor (≥pT2) was present in 30/56 (54%) patients with pure UTUC and in 18/21 (86%) patients with VH (P < 0.05). Presence of carcinoma in situ was seen in 24/56 (43%) patients with pure UTUC and in 16/21 (76%) with VH (P < 0.05). Cumulative 8/56 (14%) with pure UTUC had a nonintravesical recurrence (6 patients with local and 2 distant recurrence) compared to 8/21 (38%) (3 local, 3 nodal, 2 distant) in the subgroup with VH (P < 0.05). Opposite effect was noted for bladder recurrence: 60% for pure UTUC vs. 29% for tumors with VH (P < 0.05). Review of preoperative endoscopic biopsy did not show the presence of VH in any patients. Differences in outcomes did not reach significance: 3yr-OS 63% vs. 42% (P 0.28) and 3yr-CSS 77% vs. 50% (P 0.7)., Conclusion: Almost a third of UTUC present VH. Presence of VH is related to more aggressive tumor characteristics and associated with unfavorable outcomes. Due to a higher rate of extravesical recurrences in UTUC with VH, Follow-up controls should include cross sectional imaging and cystoscopy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)
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- 2024
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37. EAU-ESMO consensus statements on the management of advanced and variant bladder cancer-an international collaborative multi-stakeholder effort: under the auspices of the EAU and ESMO Guidelines Committees†.
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Horwich A, Babjuk M, Bellmunt J, Bruins HM, De Reijke TM, De Santis M, Gillessen S, James N, Maclennan S, Palou J, Powles T, Ribal MJ, Shariat SF, Van Der Kwast T, Xylinas E, Agarwal N, Arends T, Bamias A, Birtle A, Black PC, Bochner BH, Bolla M, Boormans JL, Bossi A, Briganti A, Brummelhuis I, Burger M, Castellano D, Cathomas R, Chiti A, Choudhury A, Compérat E, Crabb S, Culine S, De Bari B, DeBlok W, De Visschere PJL, Decaestecker K, Dimitropoulos K, Dominguez-Escrig JL, Fanti S, Fonteyne V, Frydenberg M, Futterer JJ, Gakis G, Geavlete B, Gontero P, Grubmüller B, Hafeez S, Hansel DE, Hartmann A, Hayne D, Henry AM, Hernandez V, Herr H, Herrmann K, Hoskin P, Huguet J, Jereczek-Fossa BA, Jones R, Kamat AM, Khoo V, Kiltie AE, Krege S, Ladoire S, Lara PC, Leliveld A, Linares-Espinós E, Løgager V, Lorch A, Loriot Y, Meijer R, Carmen Mir M, Moschini M, Mostafid H, Müller AC, Müller CR, N'Dow J, Necchi A, Neuzillet Y, Oddens JR, Oldenburg J, Osanto S, Oyen WJG, Pacheco-Figueiredo L, Pappot H, Patel MI, Pieters BR, Plass K, Remzi M, Retz M, Richenberg J, Rink M, Roghmann F, Rosenberg JE, Rouprêt M, Rouvière O, Salembier C, Salminen A, Sargos P, Sengupta S, Sherif A, Smeenk RJ, Smits A, Stenzl A, Thalmann GN, Tombal B, Turkbey B, Vahr Lauridsen S, Valdagni R, Van Der Heijden AG, Van Poppel H, Vartolomei MD, Veskimäe E, Vilaseca A, Vives Rivera FA, Wiegel T, Wiklund P, Williams A, Zigeuner R, and Witjes JA
- Subjects
- Delphi Technique, Europe, Humans, International Cooperation, Medical Oncology methods, Neoplasm Staging, Societies, Medical standards, Stakeholder Participation, Surveys and Questionnaires, Urinary Bladder pathology, Urinary Bladder Neoplasms pathology, Urology methods, Consensus, Medical Oncology standards, Practice Guidelines as Topic, Urinary Bladder Neoplasms therapy, Urology standards
- Abstract
Background: Although guidelines exist for advanced and variant bladder cancer management, evidence is limited/conflicting in some areas and the optimal approach remains controversial., Objective: To bring together a large multidisciplinary group of experts to develop consensus statements on controversial topics in bladder cancer management., Design: A steering committee compiled proposed statements regarding advanced and variant bladder cancer management which were assessed by 113 experts in a Delphi survey. Statements not reaching consensus were reviewed; those prioritised were revised by a panel of 45 experts before voting during a consensus conference., Setting: Online Delphi survey and consensus conference., Participants: The European Association of Urology (EAU), the European Society for Medical Oncology (ESMO), experts in bladder cancer management., Outcome Measurements and Statistical Analysis: Statements were ranked by experts according to their level of agreement: 1-3 (disagree), 4-6 (equivocal), 7-9 (agree). A priori (level 1) consensus was defined as ≥70% agreement and ≤15% disagreement, or vice versa. In the Delphi survey, a second analysis was restricted to stakeholder group(s) considered to have adequate expertise relating to each statement (to achieve level 2 consensus)., Results and Limitations: Overall, 116 statements were included in the Delphi survey. Of these, 33 (28%) statements achieved level 1 consensus and 49 (42%) statements achieved level 1 or 2 consensus. At the consensus conference, 22 of 27 (81%) statements achieved consensus. These consensus statements provide further guidance across a broad range of topics, including the management of variant histologies, the role/limitations of prognostic biomarkers in clinical decision making, bladder preservation strategies, modern radiotherapy techniques, the management of oligometastatic disease and the evolving role of checkpoint inhibitor therapy in metastatic disease., Conclusions: These consensus statements provide further guidance on controversial topics in advanced and variant bladder cancer management until a time where further evidence is available to guide our approach., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
- Published
- 2019
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38. [Unilateral renal denervation and the renal kallikrein-bradykinin system in the rat].
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Bohlender J, Nussberger J, Amstutz C, Birkhäuser F, Thalmann GN, and Imboden H
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- Animals, Biomarkers blood, Bradykinin blood, Disease Models, Animal, Hypertension blood, Hypertension metabolism, Hypertension physiopathology, Kallikreins blood, Kidney innervation, Kidney metabolism, Kidney physiopathology, Kinins blood, Male, Rats, Rats, Wistar, Treatment Outcome, Hypertension surgery, Kallikrein-Kinin System, Kidney surgery, Sympathectomy methods
- Abstract
Aim: The antihypertensive effect of renal denervation in hypertensive patients is partially explained by increased tubular natriuresis. To study the possible contribution of the kallikrein-kinin system (KKS) to this natriuretic effect in rats, we measured kallikrein activity (KA) and bradykinin concentrations (BK) in plasma and tissues., Methods: To measure KA, we adapted and validated an enzymatic assay that cleaves para-nitroaniline (pNA) from the tripeptide H-D-Pro-Phe-Arg-pNA. The coefficients of variation (CV) within- and between-assays were less than 8% for plasma and tissue KA (plasma n=6 and 13; tissue n=4). Linear results for serially diluted samples confirmed the assay specificity. Tissue BK determinations were based on an established assay for plasma BK: tissue was homogenized and kinins extracted in ethanol, and BK was isolated by high-performance (HPLC) liquid chromatography and quantitated by radioimmunassay. Within- and between-assay CV for plasma BK were 18% (n=8 and n=35, respectively) and for BK in various tissues less than 16% (n=5-8)., Results: In male Wistar rats (n=3), plasma BK was 8.2 ± 6.6 fmol/mL (mean ± SD), and tissue BK (fmol/g) in 14 tested organs varied between brain (14 ± 3) and submaxillary gland (521 ± 315). Six days after left-sided unilateral renal denervation, left renal tissue BK (89 ± 9) was not different from right renal BK (75 ± 23). Similarly, KA was comparable in the two kidneys (left 18.0 ± 1.5, right 15.8 ± 1.4 μkat/g)., Conclusion: Any possible effect of unilateral renal denervation on the kidney's KKS would have to be bilateral., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)
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- 2013
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39. [Lymphadenectomy for bladder cancer: current status and controversies].
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Metzger T, Thalmann GN, and Zehnder P
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- Humans, Laparoscopy, Lymphatic Metastasis pathology, Neoplasm Invasiveness, Prognosis, Prospective Studies, Randomized Controlled Trials as Topic, Urinary Bladder pathology, Urinary Bladder Neoplasms pathology, Cystectomy, Lymph Node Excision, Urinary Bladder Neoplasms surgery
- Abstract
Pelvic lymph node dissection is an integral part of the radical cystectomy procedure for patients with muscle-invasive bladder cancer. The optimal extent of the lymphadenectomy (LND) and mainly the proximal template boundary remain controversial issues. In view of the existing mapping studies and retrospective analyses, extended LND up to the mid-upper third of the common iliac vessels appears to provide further prognostic and therapeutic benefit and therefore should be defined as standard LND. This applies for all procedures irrespective of the choice of surgical approach (open surgery, minimally invasive approach). In this context total lymph node count is not a quality criterion because nodal yield is overly influenced by the individual patient's anatomy, surgical technique, template applied and pathological work-up. Consecutively, considerable inter-institutional differences result, which render any comparison impossible. Lymph node density is thought to be a superior prognostic factor, but it is similarly influenced by the above-mentioned factors. Concerning molecular techniques to improve the sensitivity of postoperative nodal staging further research is necessary. The two ongoing prospective randomized trials will potentially help to further define the optimal LND template.
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- 2012
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40. [Bone metastasis in prostate cancer].
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Moltzahn F and Thalmann GN
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- Humans, Male, Antibodies, Monoclonal therapeutic use, Antineoplastic Agents therapeutic use, Bone Neoplasms drug therapy, Bone Neoplasms secondary, Carcinoma drug therapy, Carcinoma secondary, Prostatic Neoplasms drug therapy
- Abstract
Bone metastasis and skeletal complications have a devastating impact on the quality of life and are a major cause of morbidity in prostate cancer patients. In addition to established bone-targeted therapies, new drugs such as endothelin A receptor antagonists, MET and VEGFR-2 antagonists or radiopharmaceuticals are in the focus of development. The standard care in prostate cancer patients with bone metastases to prevent skeletal-related events (SRE) are bisphosphonates. Denosumab, a human monoclonal antibody against RANKL, appeared to be superior to zoledronic acid for prevention of SRE and has been shown to prolong bone metastases-free survival. In contrast to zoledronic acid, denosumab clearance is not dependent on kidney function and can be administered subcutaneously. Similar rates of toxicity were observed for both substances; however, long-term data for denosumab are limited.
- Published
- 2012
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41. [Studer ileum neobladder].
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Burkhard FC, Thalmann GN, Studer UE, Schumacher M, Danuser HJ, and Zingg EJ
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- Acid-Base Imbalance physiopathology, Acid-Base Imbalance therapy, Anastomosis, Surgical methods, Catheters, Indwelling, Humans, Postoperative Care, Postoperative Complications physiopathology, Postoperative Complications therapy, Suture Techniques, Ureter surgery, Urodynamics physiology, Urinary Bladder Neoplasms surgery, Urinary Diversion methods, Urinary Reservoirs, Continent
- Published
- 2010
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42. Loss of inhibition over master pathways of bone mass regulation results in osteosclerotic bone metastases in prostate cancer.
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Rentsch CA, Cecchini MG, and Thalmann GN
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- Animals, Bone Morphogenetic Proteins antagonists & inhibitors, Bone Remodeling physiology, Carrier Proteins pharmacology, Humans, Male, Models, Animal, Osteoblasts physiology, Osteosclerosis etiology, Osteosclerosis pathology, Bone Morphogenetic Proteins physiology, Bone Neoplasms physiopathology, Bone Neoplasms secondary, Osteosclerosis physiopathology, Prostatic Neoplasms pathology, Signal Transduction physiology, Wnt Proteins physiology
- Abstract
Prostate cancer is the most common cancer among men in industrialised countries. Most patients with prostate cancer, however, will not die of it. As a result, many of them will experience symptomatic metastasis during the course of the disease. Prostate cancer has a high propensity to metastasize to bone. Unlike many other cancers prostate cancer cells induce a rather osteosclerotic than osteolytic reaction in the bone marrow by interfering with physiological bone remodelling. A proper understanding of the mechanisms of tumour cell-induced bone alterations and exaggerated bone deposition in prostate cancer may open new and urgently needed therapeutic approaches in the field of palliative care for affected patients. In this review we focus on the central role of two major regulators of bone mass, the wingless type integration site family members (WNTs) and the bone morphogenetic proteins (BMPs), in the development of osteosclerotic bone metastases.
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- 2009
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43. [Radical prostatectomy in the treatment of organ confined prostate cancer].
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Schumacher M, Thalmann GN, and Studer UE
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- Humans, Male, Organ Specificity, Practice Guidelines as Topic, Practice Patterns, Physicians', Survival Analysis, Laparoscopy methods, Prostatectomy methods, Prostatic Neoplasms surgery, Robotics methods, Surgery, Computer-Assisted methods
- Abstract
Open radical prostatectomy represents one possible therapeutic option for treating patients with clinically localized prostate cancer Patient selection and the surgical management have undergone important changes during the last years, resulting in lower morbidity and probably in a better tumor control due to a better standardisation of the surgical technique. Long-term functional outcome regarding continence and potency are of increasing importance and influence mainly the quality of life in these patients. Open radical retropubic prostatectomy remains the gold standard in patients with localized prostate cancer, due to its low morbidity and excellent oncological and functional results. The value of laparoscopic and robotic radical prostatectomy is still discussed controversially. Due to the relative high morbidity during the so-called learning curve and the lack of long-term oncological and functional results, these techniques seem to show less favourable results.
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- 2006
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44. [Old and new interventional therapies in the treatment of symptomatic benign prostate hyperplasia (BPH)].
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Müller RM, Thalmann GN, and Studer UE
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- Catheter Ablation trends, Humans, Laser Therapy trends, Male, Minimally Invasive Surgical Procedures trends, Practice Guidelines as Topic, Practice Patterns, Physicians' trends, Prostatectomy trends, Treatment Outcome, Catheter Ablation methods, Laser Therapy methods, Minimally Invasive Surgical Procedures methods, Prostatectomy methods, Prostatic Hyperplasia surgery
- Abstract
Benign Prostatic Hyperplasia is a common entity among the aging male population. Its prevalence is increasing with age and is around 80% in the over 80-years old. The androgen-estrogen ratio changes in favor of the estrogens, which leads to a growth of prostatic tissue, presenting histologically as hyperplasia. BPH can cause irritative or obstructive symptoms or both. Nowadays we speak of bladder storage or bladder voiding symptoms, summarised as LUTS (Lower Urinary Tract Symptoms). LUTS has a structural and a functional component, the structural being caused by the size of the adenoma itself the functional depending on the muscle tone of the bladder neck and the prostatic urethra. To investigate LUTS, we use validated symptom scores, sonography for residual urine and eventually a urodynamic evaluation. There are 3 grades of BPH. The indication for an interventional therapy is relative in BPH II, and absolute in BPH III. Prior to treatment, other diseases mimicking the same symptoms, have to be ruled out and adequatly treated. Electro-resection of the prostate (TUR-P) remains the standard therapy and the benchmark any new technology has to compete with. TUR-P has good short- and longterm results, but can be associated with a considerable perioperative morbidity, and the learning curve for the operator is long. The most promising of the newer techniques is the Holmium-Laser-Enucleation of the prostate (Laser-TUR-P), showing at least identical short- and median-term results, but a lower perioperative morbidity than TUR-P For several minimally-invasive techniques, indications are limited. TUMT TUNA, WIT and laser-coagulation all produce a coagulation necrosis of the prostatic tissue by thermic damage with secondary tissue shrinking. Urodynamic results however, are not comparable to TUR-P or Laser-TUR-P, and significantly more secondary interventions within 2 to 5 years are required. Minimal-invasive techniques present a favorable alternative for younger patients without complications of BPH, and for older patients with relevant comorbidities, and can usually be performed under local anaesthesia. The morbidity is low and further therapies remain possible later, if necessary.
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- 2006
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45. Simultaneous replacement of both ureters with small intestine in a woman with cystinuria.
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Schmidt J, Madersbacher S, Hochreiter WW, Thalmann GN, and Studer UE
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- Adult, Cystinuria complications, Female, Humans, Urinary Calculi complications, Cystinuria surgery, Ileum transplantation, Ureter surgery, Urinary Calculi surgery
- Published
- 2001
46. Urinary Interleukin-8 and 18 predict the response of superficial bladder cancer to intravesical therapy with bacillus Calmette-Guerin.
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Thalmann GN, Sermier A, Rentsch C, Möhrle K, Cecchini MG, and Studer UE
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- Administration, Intravesical, Aged, Aged, 80 and over, Carcinoma, Transitional Cell diagnosis, Carcinoma, Transitional Cell urine, Enzyme-Linked Immunosorbent Assay, Female, Follow-Up Studies, Humans, Immunotherapy, Male, Middle Aged, Neoplasm Recurrence, Local diagnosis, Predictive Value of Tests, Sensitivity and Specificity, Treatment Outcome, Urinary Bladder Neoplasms diagnosis, Urinary Bladder Neoplasms urine, BCG Vaccine therapeutic use, Carcinoma, Transitional Cell therapy, Interleukin-18 urine, Interleukin-8 urine, Urinary Bladder Neoplasms therapy
- Abstract
Purpose: We evaluate the predictive value of urinary cytokine levels of interleukin (IL) 8 and 18 for response in patients receiving intravesical bacillus Calmette-Guerin (BCG) for prevention of recurrences of superficial bladder cancer and treatment of carcinoma in situ., Materials and Methods: In 28 patients with superficial bladder cancer treated with BCG IL-8 expression in the urine during the first 6 hours after the first BCG instillation was determined. In 17 patients IL-18 levels were also evaluated during the first 12 hours after BCG instillation. IL-8 and 18 levels were determined by solid phase double ligand enzyme-linked immunosorbent assay., Results: In 12 of the 28 patients assessed for IL-8 expression disease recurred after a median followup of 66 months. Median IL-8 expression during the first 6 hours for these patients was 851 ng. (range 232 to 8,497). Median IL-8 expression during the first 6 hours in patients without recurrence was 4,200 ng. (range 432 to 12, 232). Of 8 patients with a followup of greater than 36 months 7 (88%) had no recurrent disease and IL-8 levels greater than 4,000 ng. Patients secreting more than 4,000 ng. IL-8 into the urine after BCG have a significantly higher chance of remaining disease-free (p <0.05), and those with elevated IL-18 expression have a significantly longer disease-free survival (p <0.05). After a median followup of 23 months (range 7 to 93) 6 of the 17 patients assessed for IL-18 expression had treatment failure. Median IL-18 expression in those patients during the first 12 hours was 2,632 pg. (range 860 to 8,298). Median IL-18 expression during the first 12 hours in patients without recurrence was 12,258 pg. (range 1,727 to 151,495)., Conclusions: In this study we confirmed the value of quantitative IL-8 expression in the urine during the first 6 hours after BCG instillation for superficial bladder cancer to predict freedom of disease. Furthermore, to our knowledge we report for the first time the potential value of IL-18 expression in the urine during the first 12 hours after BCG to predict freedom from disease. These findings may help improve the treatment of patients with superficial bladder cancer, especially by identifying those with a high risk of disease recurrence and progression after BCG therapy.
- Published
- 2000
47. LNCaP progression model of human prostate cancer: androgen-independence and osseous metastasis.
- Author
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Thalmann GN, Sikes RA, Wu TT, Degeorges A, Chang SM, Ozen M, Pathak S, and Chung LW
- Subjects
- Animals, Blotting, Northern, Cell Line, Dihydrotestosterone pharmacology, Gene Expression Regulation, Neoplastic, Gentian Violet chemistry, Histocytochemistry, Humans, Image Processing, Computer-Assisted, Immunoenzyme Techniques, Karyotyping, Male, Mice, Mice, Inbred BALB C, Mice, Nude, Orchiectomy, Prostate-Specific Antigen blood, Prostatic Neoplasms genetics, RNA, Neoplasm chemistry, Specific Pathogen-Free Organisms, Tumor Cells, Cultured, Bone Neoplasms secondary, Disease Models, Animal, Osteosarcoma secondary, Prostatic Neoplasms pathology
- Abstract
Background: Clinically, the lethal phenotypes of human prostate cancer are characterized by their progression to androgen-independence and their propensity to form osseous metastases. We reported previously on the establishment of androgen-independent (AI) human prostate cancer cell lines derived from androgen-dependent (AD) LNCaP cells, with androgen independence defined as the capability of prostate cancer cells to grow in castrated hosts. One of the sublines, C4-2, was found to be AI, highly tumorigenic, and metastatic, having a proclivity for metastasis to the bone., Methods: We established the AI and bone metastatic cell sublines B2, B3, B4, and B5 from the parental C4-2 subline, using a previously established coinoculating procedure. We determined the biologic behavior of the parental and derivative LNCaP sublines in vivo and in vitro, as well as their molecular and cytogenetic characteristics., Results: Unlike other human prostate cancer models, the LNCaP progression model shares remarkable similarities with human prostate cancer. We observed a comparable pattern of metastasis from the primary to the lymph node and to the axial skeleton, with a predominant phenotype of osteoblastic reaction; 25-37.5% of the animals developed paraplegia. Cytogenetic and biochemical characterizations of LNCaP sublines also indicate close similarities between human prostate cancer and the LNCaP progression model. Additional chromosomal changes were detected in B2-B5 sublines derived from C4-2 bone metastases. These LNCaP sublines were found to grow faster under anchorage-dependent but not -independent conditions. The in vitro invasion and in vivo metastatic potential of these LNCaP sublines surprisingly correlated with anchorage-dependent and not -independent growth. The derivative LNCaP sublines when cultured in vitro produced a substantially higher (20-30-fold) amount of basal steady-state concentrations of PSA than that of the parental LNCaP cells. PSA production was high initially, but was markedly reduced when the derivative cell lines were inoculated and allowed to grow long-term in vivo for the establishment of tumors and metastasis, suggesting that unknown host factors derived either from the prostate or the bone can effectively downregulate PSA expression by prostate tumor epithelium., Conclusions: The LNCaP model of human prostate cancer progression will help improve our understanding of the mechanisms of androgen-independence and osseous metastasis, and tumor-host determinants of PSA expression., (Copyright 2000 Wiley-Liss, Inc.)
- Published
- 2000
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48. Transurethral thermotherapy for benign prostatic hyperplasia significantly decreases infravesical obstruction: results in 134 patients after 1 year.
- Author
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Thalmann GN, Graber SF, Bitton A, Burkhard FC, Gruenig O, and Studer UE
- Subjects
- Aged, Aged, 80 and over, Humans, Male, Middle Aged, Prospective Studies, Prostatic Hyperplasia complications, Prostatic Hyperplasia diagnostic imaging, Prostatic Hyperplasia physiopathology, Time Factors, Ultrasonography, Urethra, Urinary Bladder Neck Obstruction etiology, Urinary Bladder Neck Obstruction physiopathology, Urodynamics, Diathermy, Microwaves therapeutic use, Prostatic Hyperplasia therapy, Urinary Bladder Neck Obstruction therapy
- Abstract
Purpose: We prospectively evaluated a decrease in outflow obstruction caused by benign prostatic hyperplasia (BPH) with second generation thermotherapy., Materials and Methods: Transurethral microwave therapy was given with local anesthesia to 134 patients with urodynamically and cystoscopically documented obstruction by BPH and preserved detrusor function. Of 134 patients 67 (50%) had a general health score of 3 or greater., Results: Urgency was the main complaint during thermotherapy. After a median followup of 24 months (minimum 12) 100 patients were evaluable at 6 and 12 months. Of the initial 134 patients 17 (13%) who required additional treatment (repeat thermotherapy, transurethral prostatic resection, permanent cystostomy), 7 who died during followup for treatment unrelated reasons and 10 who were lost to followup or refused evaluation were excluded from further analysis. Mean International Prostate Symptom Score decreased from 22.5 before to 3.6 at 6 months after treatment and remained stable at 12 months. Mean Quality of Life Index improved from 4.3 before to 1 at 12 months after treatment. Mean maximum flow increased from 7.3 ml. per second before to 14.5 at 6 months and 13.9 at 12 months after treatment. Mean post-void residual decreased from 199 to 34.8 and 37.2 ml. at 6 and 12 months, respectively. Urodynamic evaluation of 84 patients after 6 months revealed a decrease in mean detrusor opening pressure from 96.8 to 53 cm. water and mean detrusor pressure at maximum flow from 99.8 to 59.7 cm. water. Mean ultrasonographic prostate volume decreased from 57.6 to 42.4 cc and a cavity in the prostate was documented in 65 of the 84 cases (77%). All changes between the pretreatment and posttreatment values at 6 and 12 months, respectively, were statistically significant (paired t test p<0.00001)., Conclusions: Targeted transurethral thermotherapy with second generation microwave equipment is minimally invasive, easy to apply and generally well tolerated with local anesthesia. Infravesical outlet obstruction and voiding pressures as assessed by pressure flow studies significantly decreased 6 months after treatment. Subjective voiding symptoms as well as post-void residual urine were significantly decreased, and urinary flow was improved 6 and 12 months after treatment of documented BPH.
- Published
- 1999
49. Osteopontin: possible role in prostate cancer progression.
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Thalmann GN, Sikes RA, Devoll RE, Kiefer JA, Markwalder R, Klima I, Farach-Carson CM, Studer UE, and Chung LW
- Subjects
- Animals, Blotting, Western, Cell Division drug effects, Cells, Cultured, Culture Media, Conditioned pharmacology, Disease Progression, Flow Cytometry, Humans, Immunohistochemistry, Male, Mice, Osteopontin, Prostatic Neoplasms pathology, Prostatic Neoplasms secondary, RNA biosynthesis, Rats, Sialoglycoproteins biosynthesis, Sialoglycoproteins pharmacology, Prostatic Neoplasms metabolism, Sialoglycoproteins physiology
- Abstract
Human prostate cancer has the propensity to metastasize to the bone where reciprocal cellular interactions between prostate cancer and bone cells are known to occur. Osteopontin (OPN), a noncollagenous bone extracellular matrix, is a secreted adhesive glycoprotein with a functional RGD cell-binding domain that interacts with the alpha(v)beta3 cell surface integrin heterodimer. OPN has been associated with malignant transformation as well as being ligand to the CD44 receptor. Polyclonal antibodies to human OPN (hOPN) were prepared, and specificity was shown by preabsorption with recombinant hOPN. The stimulatory effect of hOPN protein and the inhibitory effect of hOPN antibody on human prostate cancer cell lines LNCaP and C4-2 were assessed by induction or inhibition of anchorage-independent growth, respectively. Expression of hOPN mRNA in prostate cancer cell lines and human prostate cancer tissue specimens were measured by mRNA blot analysis. Protein expression was assessed by immunohistochemistry in human prostate cancer specimens and by Western blot analysis in prostate cancer cell lines. hOPN stimulated anchorage-independent growth of the human prostate cancer cell lines LNCaP and C4-2 in vitro. Antibodies to hOPN inhibited the growth-stimulatory effect by endogenous OPN, which can be overcome by the addition of exogenous hOPN. hOPN mRNA and protein are expressed in human prostate cancer cell lines in vitro and in clinical human prostate cancer specimens. These findings taken together suggest that OPN may act as a paracrine and autocrine mediator of prostate cancer growth and progression.
- Published
- 1999
50. Establishing human prostate cancer cell xenografts in bone: induction of osteoblastic reaction by prostate-specific antigen-producing tumors in athymic and SCID/bg mice using LNCaP and lineage-derived metastatic sublines.
- Author
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Wu TT, Sikes RA, Cui Q, Thalmann GN, Kao C, Murphy CF, Yang H, Zhau HE, Balian G, and Chung LW
- Subjects
- Animals, Lymphatic Metastasis pathology, Male, Mice, Mice, Nude, Mice, SCID, Polymerase Chain Reaction methods, Transcription, Genetic, Transplantation, Heterologous, Tumor Cells, Cultured pathology, Bone Neoplasms secondary, Osteoblasts metabolism, Prostate-Specific Antigen metabolism, Prostatic Neoplasms pathology
- Abstract
LNCaP lineage-derived human prostate cancer cell lines C4-2 and C4-2B4 acquire androgen independence and osseous metastatic potential in vivo. Using C4-2 and C4-2B4 the goals of the current investigation were 1) to establish an ideal bone xenograft model for prostate cancer cells in intact athymic or SCID/bg mice using an intraosseous route of tumor cell administration and 2) to compare prostate cancer metastasis by administering cells either through intravenous (i.v.) or intracardiac administration in athymic or SCID/bg mice. Subsequent to tumor cell administration, prostate cancer growth in the skeleton was assessed by radiographic bone density, serum prostate-specific antigen (PSA) levels, presence of hematogenous prostate cancer cells and histopathologic evaluation of tumor specimens in the lymph node and skeleton. Our results show that whereas LNCaP cells injected intracardially failed to develop metastasis, C4-2 cells injected similarly had the highest metastatic capability in SCID/bg mice. Retroperitoneal and mediastinal lymph node metastases were noted in 3/7 animals, whereas 2/7 animals developed osteoblastic spine metastases. Intracardiac injection of C4-2 in athymic hosts produced spinal metastases in 1/5 animals at 8-12 weeks post-injection; PC-3 injected intracardially also metastasized to the bone but yielded osteolytic responses. Intravenous injection of either LNCaP or C4-2 failed to establish tumor colonies. Intrailiac injection of C4-2 but not LNCaP nor C4-2B4 cells in athymic mice established rapidly growing tumors in 4/8 animals at 2-7 weeks after inoculation. Intrafemoral injection of C4-2 (9/16) and C4-2B4 (5/18) but not LNCaP (0/13) cells resulted in the development of osteoblastic bone lesions in athymic mice (mean: 6 weeks, range: 3-12 weeks). In SCID/bg mice, intrafemoral injection of LNCaP (6/8), C4-2 (8/8) and C4-2B4 (8/8) cells formed PSA-producing, osteoblastic tumors in the bone marrow space within 3-5 weeks after tumor cell inoculation. A stepwise increase of serum PSA was detected in all animals. Reverse transcription-polymerase chain reaction (RT-PCR) to detect hematogenously disseminated prostate cancer cells could not be correlated to either serum PSA level or histological evidence of tumor cells in the marrow space. We have thus established a PSA-producing and osteoblastic human prostate cancer xenograft model in mice.
- Published
- 1998
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