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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

Author

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.

Published
2022
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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

Author

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.

Published
2015
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12. 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

Author

Horwich, A, Babjuk, M, Bellmunt, J, Bruins, H M, Reijke, T M De, Santis, M De, Gillessen, S, James, N, Maclennan, S, Palou, J, Powles, T, Ribal, M J, Shariat, S F, Kwast, T Van Der, 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, Compérat, E, Crabb, S, Culine, S, Bari, B De, Blok, W De, 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, Grubmüller, 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-Espinós, E, Løgager, V, Lorch, A, Loriot, Y, Meijer, R, Mir, M Carmen, Moschini, M, Mostafid, H, Müller, A-C, Müller, 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, Rouprêt, M, Rouvière, O, Salembier, C, Salminen, A, Sargos, P, Sengupta, S, Sherif, Amir, Smeenk, R J, Smits, A, Stenzl, A, Thalmann, G N, Tombal, B, Turkbey, B, Lauridsen, S Vahr, Valdagni, R, Van Der Heijden, A G, Van Poppel, H, Vartolomei, M D, Veskimäe, E, Vilaseca, A, Rivera, F A Vives, Wiegel, T, Wiklund, P, Williams, A, Zigeuner, R, Witjes, J A, Horwich, A, Babjuk, M, Bellmunt, J, Bruins, H M, Reijke, T M De, Santis, M De, Gillessen, S, James, N, Maclennan, S, Palou, J, Powles, T, Ribal, M J, Shariat, S F, Kwast, T Van Der, 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, Compérat, E, Crabb, S, Culine, S, Bari, B De, Blok, W De, 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, Grubmüller, 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-Espinós, E, Løgager, V, Lorch, A, Loriot, Y, Meijer, R, Mir, M Carmen, Moschini, M, Mostafid, H, Müller, A-C, Müller, 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, Rouprêt, M, Rouvière, O, Salembier, C, Salminen, A, Sargos, P, Sengupta, S, Sherif, Amir, Smeenk, R J, Smits, A, Stenzl, A, Thalmann, G N, Tombal, B, Turkbey, B, Lauridsen, S Vahr, Valdagni, R, Van Der Heijden, A G, Van Poppel, H, Vartolomei, M D, Veskimäe, E, Vilaseca, A, Rivera, F A Vives, Wiegel, T, Wiklund, P, Williams, A, Zigeuner, R, and Witjes, J A

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 sta

Published
2019
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13. 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†.

Author

UCL - SSS/IREC/CHEX - Pôle de chirgurgie expérimentale et transplantation, UCL - (SLuc) Service d'urologie, Witjes, J A, Van Der Heijden, A G, Smits, A, Stenzl, A, Thalmann, G N, Tombal, Bertrand, Turkbey, B, Lauridsen, S Vahr, Valdagni, R, Van Poppel, H, Sherif, A, Vartolomei, M D, Veskimäe, E, Vilaseca, A, Rivera, F A Vives, Wiegel, T, Wiklund, P, Williams, A, Zigeuner, R, Smeenk, R J, Horwich, A, Babjuk, M, Bellmunt, J, Bruins, H M, Reijke, T M De, Santis, M De, Gillessen, S, James, N, Maclennan, S, Palou, J, Powles, T, Ribal, M J, Shariat, S F, Kwast, T Van Der, 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, Compérat, E, Crabb, S, Culine, S, Bari, B De, Blok, W De, 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, Grubmüller, 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-Espinós, E, Løgager, V, Lorch, A, Loriot, Y, Meijer, R, Mir, M Carmen, Moschini, M, Mostafid, H, Müller, A-C, Müller, 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, Rouprêt, M, Rouvière, O, Salembier, C, Salminen, A, Sargos, P, Sengupta, S, UCL - SSS/IREC/CHEX - Pôle de chirgurgie expérimentale et transplantation, UCL - (SLuc) Service d'urologie, Witjes, J A, Van Der Heijden, A G, Smits, A, Stenzl, A, Thalmann, G N, Tombal, Bertrand, Turkbey, B, Lauridsen, S Vahr, Valdagni, R, Van Poppel, H, Sherif, A, Vartolomei, M D, Veskimäe, E, Vilaseca, A, Rivera, F A Vives, Wiegel, T, Wiklund, P, Williams, A, Zigeuner, R, Smeenk, R J, Horwich, A, Babjuk, M, Bellmunt, J, Bruins, H M, Reijke, T M De, Santis, M De, Gillessen, S, James, N, Maclennan, S, Palou, J, Powles, T, Ribal, M J, Shariat, S F, Kwast, T Van Der, 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, Compérat, E, Crabb, S, Culine, S, Bari, B De, Blok, W De, 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, Grubmüller, 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-Espinós, E, Løgager, V, Lorch, A, Loriot, Y, Meijer, R, Mir, M Carmen, Moschini, M, Mostafid, H, Müller, A-C, Müller, 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, Rouprêt, M, Rouvière, O, Salembier, C, Salminen, A, Sargos, P, and Sengupta, S

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 sta

Published
2019

14. 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†

Author

Cancer, Verpleegkundig Specialisten, MS Urologische Oncologie, Horwich, A, Babjuk, M, Bellmunt, J, Bruins, H M, Reijke, T M De, Santis, M De, Gillessen, S, James, N, Maclennan, S, Palou, J, Powles, T, Ribal, M J, Shariat, S F, Kwast, T Van Der, 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, Compérat, E, Crabb, S, Culine, S, Bari, B De, Blok, W De, 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, Grubmüller, 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-Espinós, E, Løgager, V, Lorch, A, Loriot, Y, Meijer, R, Mir, M Carmen, Moschini, M, Mostafid, H, Müller, A-C, Müller, 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, Rouprêt, M, Rouvière, 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 Vahr, Valdagni, R, Van Der Heijden, A G, Van Poppel, H, Vartolomei, M D, Veskimäe, E, Vilaseca, A, Rivera, F A Vives, Wiegel, T, Wiklund, P, Williams, A, Zigeuner, R, Witjes, J A, Cancer, Verpleegkundig Specialisten, MS Urologische Oncologie, Horwich, A, Babjuk, M, Bellmunt, J, Bruins, H M, Reijke, T M De, Santis, M De, Gillessen, S, James, N, Maclennan, S, Palou, J, Powles, T, Ribal, M J, Shariat, S F, Kwast, T Van Der, 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, Compérat, E, Crabb, S, Culine, S, Bari, B De, Blok, W De, 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, Grubmüller, 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-Espinós, E, Løgager, V, Lorch, A, Loriot, Y, Meijer, R, Mir, M Carmen, Moschini, M, Mostafid, H, Müller, A-C, Müller, 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, Rouprêt, M, Rouvière, 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 Vahr, Valdagni, R, Van Der Heijden, A G, Van Poppel, H, Vartolomei, M D, Veskimäe, E, Vilaseca, A, Rivera, F A Vives, Wiegel, T, Wiklund, P, Williams, A, Zigeuner, R, and Witjes, J A

Published
2019

15. 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†

Author

Horwich, A., Babjuk, M., Bellmunt, J., Bruins, H. M., Reijke, T. M.De, Santis, M. De, Gillessen, S., James, N., Maclennan, S., Palou, J., Powles, T., Ribal, M. J., Shariat, S. F., Kwast, T. Van Der, 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., Compérat, E., Crabb, S., Culine, S., Bari, B. De, Blok, W. De, 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., Grubmüller, 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-Espinós, E., Løgager, V., Lorch, A., Loriot, Y., Meijer, R., Mir, M. Carmen, Moschini, M., Mostafid, H., Müller, A. C., Müller, 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., Rouprêt, M., Rouvière, 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. Vahr, Valdagni, R., Van Der Heijden, A. G., Van Poppel, H., Vartolomei, M. D., Veskimäe, E., Vilaseca, A., Rivera, F. A.Vives, Wiegel, T., Wiklund, P., Williams, A., Zigeuner, R., Witjes, J. A., Horwich, A., Babjuk, M., Bellmunt, J., Bruins, H. M., Reijke, T. M.De, Santis, M. De, Gillessen, S., James, N., Maclennan, S., Palou, J., Powles, T., Ribal, M. J., Shariat, S. F., Kwast, T. Van Der, 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., Compérat, E., Crabb, S., Culine, S., Bari, B. De, Blok, W. De, 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., Grubmüller, 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-Espinós, E., Løgager, V., Lorch, A., Loriot, Y., Meijer, R., Mir, M. Carmen, Moschini, M., Mostafid, H., Müller, A. C., Müller, 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., Rouprêt, M., Rouvière, 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. Vahr, Valdagni, R., Van Der Heijden, A. G., Van Poppel, H., Vartolomei, M. D., Veskimäe, E., Vilaseca, A., Rivera, F. A.Vives, Wiegel, T., Wiklund, P., Williams, A., Zigeuner, R., and Witjes, J. A.

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

Published
2019

16. Extragonadal retroperitoneal germ cell tumor: evidence of origin in the testis

Author

Scholz, M., Zehender, M., Thalmann, G. N., Borner, M., Thöni, H., Studer, U. E., Scholz, M., Zehender, M., Thalmann, G. N., Borner, M., Thöni, H., and Studer, U. E.

Abstract

Background The origin of extragonadal retroperitoneal germ cell tumors remains controversial. Whether they develop primarily in the retroperitoneum or whether they are metastases of a primary testicular tumor has long been debated. Patients and methods We retrospectively analyzed 26 patients treated as having primary extragonadal retroperitoneal germ cell tumors based upon the findings of testicular palpation by the referring physician. Testicular evaluation was then extended with ultrasonographical and histological examinations. Results Biopsy of the extragonadal tumor was performed in 25 patients, confirming diagnosis of extragonadal retroperitoneal germ cell tumor. Prior to treatment patients were clinically evaluated by several physicians and the testes were not considered suspicious for testicular cancer. At urological workup, testes were found to be atrophic and/or indurated in 14 (54%) patients, enlarged in one (4%) and unremarkable in 11 (42%). Ultrasound examination of the testes in 20 patients showed pathological findings in all of them. Histology of the testis was available in 25 of 26 patients and revealed active tumor in three, intratubular germ cell neoplasia in four, scar tissue in 12, sclerosis in three, sclerosis and fibrosis in one, and fibrosis alone in two. Conclusions So-called primary extragonadal germ cell tumors in the retroperitoneum are very likely a rare or non-existing entity and should be considered as metastases of a viable or burned-out testicular cancer until proven otherwise. All of our patients with histologically examined testes had pathological finding, 76% of which were either viable tumor or scars

Published
2017

17. Impact of perioperative chemotherapy on survival in patients with advanced primary urethral cancer: results of the international collaboration on primary urethral carcinoma

Author

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., Efstathiou, J. A., 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.

Abstract

This is the first series that suggests a prognostic benefit of neoadjuvant treatment in a consecutive series of patients who underwent perioperative chemotherapy plus surgery for advanced primary urethral carcinoma. Further studies should yield a better understanding of how perioperative chemotherapy exerts a positive effect on survival in order to selectively advocate its use in advanced primary urethral carcinoma

Published
2017

18. La dénervation rénale unilatérale et le système kallikréine-bradykinine rénal chez le rat

Author

Thalmann, G. N., Birkhäuser, F., Imboden, H., Bohlender, J., Nussberger, J., and Amstutz, C.

Subjects
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.

Published
2013
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19. [Bone metastasis in prostate cancer]

Author

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.

Published
2012
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20. [Lymphadenectomy for bladder cancer: current status and controversies]

Author

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.

Published
2012
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22. 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

Author

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

Subjects
10062 Urological Clinic, Cancer Research, Oncology, 610 Medicine & health, 2730 Oncology, 1306 Cancer Research
Published
2009
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23. Nuclear iASPP may facilitate prostate cancer progression

Author

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

Published
2014
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24. Everolimus as first-line therapy in nonrapidly progressive metastatic castration-resistant prostate cancer (mCRPC): A multicenter phase II trial (SAKK 08/08).

Author

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

Published
2011
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33. Lymphadenektomie im Rahmen der radikalen Zystektomie : Aktueller Stand und Kontroversen.

Author

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]

Published
2012
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39. Extragonadal retroperitoneal germ cell tumor: evidence of origin in the testis

Author

Scholz, M., Zehender, M., Thalmann, G. N., Borner, M., Thöni, H., Studer, U. E., Scholz, M., Zehender, M., Thalmann, G. N., Borner, M., Thöni, H., and Studer, U. E.

Abstract

Background The origin of extragonadal retroperitoneal germ cell tumors remains controversial. Whether they develop primarily in the retroperitoneum or whether they are metastases of a primary testicular tumor has long been debated. Patients and methods We retrospectively analyzed 26 patients treated as having primary extragonadal retroperitoneal germ cell tumors based upon the findings of testicular palpation by the referring physician. Testicular evaluation was then extended with ultrasonographical and histological examinations. Results Biopsy of the extragonadal tumor was performed in 25 patients, confirming diagnosis of extragonadal retroperitoneal germ cell tumor. Prior to treatment patients were clinically evaluated by several physicians and the testes were not considered suspicious for testicular cancer. At urological workup, testes were found to be atrophic and/or indurated in 14 (54%) patients, enlarged in one (4%) and unremarkable in 11 (42%). Ultrasound examination of the testes in 20 patients showed pathological findings in all of them. Histology of the testis was available in 25 of 26 patients and revealed active tumor in three, intratubular germ cell neoplasia in four, scar tissue in 12, sclerosis in three, sclerosis and fibrosis in one, and fibrosis alone in two. Conclusions So-called primary extragonadal germ cell tumors in the retroperitoneum are very likely a rare or non-existing entity and should be considered as metastases of a viable or burned-out testicular cancer until proven otherwise. All of our patients with histologically examined testes had pathological finding, 76% of which were either viable tumor or scars

40. Impact of perioperative chemotherapy on survival in patients with advanced primary urethral cancer: results of the international collaboration on primary urethral carcinoma

Author

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., Efstathiou, J. A., 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.

Abstract

This is the first series that suggests a prognostic benefit of neoadjuvant treatment in a consecutive series of patients who underwent perioperative chemotherapy plus surgery for advanced primary urethral carcinoma. Further studies should yield a better understanding of how perioperative chemotherapy exerts a positive effect on survival in order to selectively advocate its use in advanced primary urethral carcinoma

41. 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)

Author

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

Subjects
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

42. A Systematic Review of the Role of Definitive Local Treatment in Patients with Clinically Lymph Node-positive Prostate Cancer

Author

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.

Subjects
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

43. A 2-center review of histopathology of variants of upper urinary tract urothelial carcinoma and their impact on clinical outcomes.

Author

Giudici N, Schoch A, Genitsch V, Rodriguez-Calero A, Thalmann GN, and Seiler R

Subjects
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.)

Published
2024
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44. 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†.

Author

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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45. [Unilateral renal denervation and the renal kallikrein-bradykinin system in the rat].

Author

Bohlender J, Nussberger J, Amstutz C, Birkhäuser F, Thalmann GN, and Imboden H

Subjects
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.)

Published
2013
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46. [Bone metastasis in prostate cancer].

Author

Moltzahn F and Thalmann GN

Subjects
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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47. [Studer ileum neobladder].

Author

Burkhard FC, Thalmann GN, Studer UE, Schumacher M, Danuser HJ, and Zingg EJ

Subjects
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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48. Loss of inhibition over master pathways of bone mass regulation results in osteosclerotic bone metastases in prostate cancer.

Author

Rentsch CA, Cecchini MG, and Thalmann GN

Subjects
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.

Published
2009
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49. [Radical prostatectomy in the treatment of organ confined prostate cancer].

Author

Schumacher M, Thalmann GN, and Studer UE

Subjects
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.

Published
2006
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50. [Old and new interventional therapies in the treatment of symptomatic benign prostate hyperplasia (BPH)].

Author

Müller RM, Thalmann GN, and Studer UE

Subjects
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.

Published
2006
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