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2. 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., 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., Compérat, E., Crabb, S., Culine, S., De Bari, B., DeBlok, 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., 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., Carmen Mir, M., 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., Vahr Lauridsen, S., Valdagni, R., Van Der Heijden, A.G., Van Poppel, H., Vartolomei, M.D., Veskimäe, E., Vilaseca, A., Vives Rivera, F.A., Wiegel, T., Wiklund, P., Williams, A., Zigeuner, R., and Witjes, J.A.

Published
2019
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5. Survival outcomes of patients with muscle-invasive bladder cancer according to pathological response at radical cystectomy with or without neo-adjuvant chemotherapy: a case–control matching study

Author

van Ginkel, Noor, Hermans, Tom J. N., Meijer, Dennie, Boormans, Joost L., Voortman, Jens, Mertens, Laura, van Beek, Sytse C., Vis, André N., Aben, K. K. H., Arends, T. J., Ausems, P. J., Baselmans, D., Berger, C. P. A. M., Berrens, A. C., Bickerstaffe, H., Bos, S. D., Braam, M., Buddingh, K. T., Claus, S., Dekker, K., van Doeveren, T., Einerhand, S. M. H., Fossion, L. M. C. L., van Gennep, E. J., Grondhuis Palacios, L. A., Hinsenveld, F. J., Hobijn, M. M., van Huystee, S. H., Jaspers-Valentijn, M., Klaver, O. S., Koldewijn, E. L., Korsten, L., Lenting, A., Lentjes, K. J., Luiting, H. B., van der Meer, S., Nieuwenhuijzen, J. A., Noordzij, M. A., Nooter, R. I., Notenboom, C. A. W., Oomen, R. J. A., van der Poel, H. G., van Roermund, J. G. H., de Rooij, J., Roshani, H., van der Schoot, D. K. E., Schrier, B. P., van der Slot, M. A., Somford, D. M., Stelwagen, P. J., Stroux, A. M. A., van der West, A., Wijsman, B. P., Windt, W. A. K. M., van Zanten, P., IOO, Urology, Cancer Center Amsterdam, Internal medicine, CCA - Cancer Treatment and quality of life, Other Research, MUMC+: MA Urologie (9), MUMC+: MA AIOS Urologie (9), RS: FHML non-thematic output, CCA - Biomarkers, CCA - Imaging and biomarkers, and Otolaryngology / Head & Neck Surgery

Subjects
Urology, Muscles, Response, Prognosis, Cystectomy, Neoadjuvant Therapy, SDG 3 - Good Health and Well-being, Urinary Bladder Neoplasms, Nephrology, Chemotherapy, Adjuvant, Urological cancers Radboud Institute for Health Sciences [Radboudumc 15], Case-Control Studies, Chemotherapy, Humans, Neoplasm Invasiveness, Muscle-invasive bladder cancer, Retrospective Studies
Abstract

Objectives To assess survival of patients with muscle-invasive bladder cancer (MIBC) who underwent radical cystectomy (RC) with or without neo-adjuvant chemotherapy (NAC) according to the pathological response at RC. Methods 965 patients with MIBC (cT2-4aN0M0) who underwent RC with or without NAC were analyzed. Among the collected data were comorbidity, clinical and pathological tumor stage, tumor grade, nodal status (y)pN, and OS. Case–control matching of 412 patients was performed to compare oncological outcomes. Kaplan–Meier curves were created to estimate OS for patients who underwent RC with or without NAC, and for those with complete response (pCR), partial response (pPR), or residual or progressive disease (PD). Results Patients with a pCR or pPR at RC, with or without NAC, had better OS than patients who had PD (both p values p p = 0.023). Conclusions This study showed that patients with MIBC who underwent NAC with RC had a significant better OS than those who underwent RC only. The proportion of patients with a pCR was higher in those who received NAC and RC than in those who were treated by RC only. The favorable OS rate in the NAC and RC cohort was probably attributed to the higher observed pCR rate.

Published
2022
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6. EAU-ESMO consensus statements on the management of advanced and variant bladder cancer

Author

Witjes JA, 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, Comperat E, Crabb S, Culine S, De Bari B, De Blok 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, Grubmuller 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-Espinos E, Logager V, Lorch A, Loriot Y, Meijer R, Mir MC, Moschini M, Mostafid H, Muller AC, Muller 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, Roupret M, Rouviere O, Salembier C, Salminen A, Sargos P, Sengupta S, Sherif A, Smeenk RJ, Smits A, Stenzl A, Thalmann GN, Tombal B, Turkbey B, Lauridsen SV, Valdagni R, Van der Heijden AG, Van Poppel H, Vartolomei MD, Veskimae E, Vilaseca A, Rivera FAV, Wiegel T, Wiklund P, Williams A, Zigeuner R, Horwich A, Witjes JA, 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, Der Kwast TV, 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, De Blok W, J L De Visschere P, 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, Mir MC, Moschini M, Mostafid H, Müller AC, Müller CR, N'Dow J, Necchi A, Neuzillet Y, Oddens JR, Oldenburg J, Osanto S, J G Oyen W, 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, Lauridsen SV, Valdagni R, Der Heijden AGV, Van Poppel H, Vartolomei MD, Veskimäe E, Vilaseca A, Rivera FAV, Wiegel T, Wiklund P, Williams A, Zigeuner R, Horwich A., UCL - SSS/IREC/CHEX - Pôle de chirgurgie expérimentale et transplantation, UCL - (SLuc) Service d'urologie, Witjes, Ja, 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, Comperat, E, Crabb, S, Culine, S, De Bari, B, De Blok, 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, Grubmuller, 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-Espinos, E, Logager, V, Lorch, A, Loriot, Y, Meijer, R, Mir, Mc, Moschini, M, Mostafid, H, Muller, Ac, Muller, 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, Roupret, M, Rouviere, O, Salembier, C, Salminen, A, Sargos, P, Sengupta, S, Sherif, A, Smeenk, Rj, Smits, A, Stenzl, A, Thalmann, Gn, Tombal, B, Turkbey, B, Lauridsen, Sv, Valdagni, R, Van der Heijden, Ag, Van Poppel, H, Vartolomei, Md, Veskimae, E, Vilaseca, A, Rivera, Fav, Wiegel, T, Wiklund, P, Williams, A, Zigeuner, R, and Horwich, A

Subjects
Treatment, Consensus, Follow-up, education, Bladder cancer, Diagnosis, Consensu, Delphi, Diagnosi
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 prior to 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), and 7-9 (agree). A priori (level 1) consensus was defined as >= 70% agreement and

Published
2020
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9. Intermediate-term survival of robot-assisted versus open radical cystectomy for muscle-invasive and high-risk non-muscle invasive bladder cancer in The Netherlands

Author

Hinsenveld, Florentien J., Boormans, Joost L., van der Poel, Henk G., van der Schoot, Deric K.E., Vis, André N., Aben, Katja K.H., Arends, T. J., Ausems, P. J., Baselmans, D., Berger, C. P.A.M., Berrens, A., Bickerstaffe, H., Bos, S. D., Braam, M., Buddingh, K. T., Claus, S., Dekker, K., van Doeveren, T., Einerhand, S.M.H., Fossion, L. M.C.L., van Gennep, E. J., van Ginkel, N., Palacios, LA Grondhuis, Hermans, T. J.N., Hobijn, M. M., van Huystee, S. H., Jaspers-Valentijn, M., Klaver, O.S., Koldewijn, E. L., Korsten, L., Lenting, A., Lentjes, K. J., Luiting, H. B., van der Meer, S., Nieuwenhuijzen, J. A., Noordzij, M. A., Nooter, R. I., Notenboom, C. A.W., Oomen, R. J.A., van Roermund, J. G.H., de Rooij, J., Roshani, H., Schrier, B. P., van der Slot, M. A., Somford, D. M., Stelwagen, P. J., Stroux, A. M.A., van der West, A., Wijsman, B. P., van Beek, Sytse C., Hinsenveld, Florentien J., Boormans, Joost L., van der Poel, Henk G., van der Schoot, Deric K.E., Vis, André N., Aben, Katja K.H., Arends, T. J., Ausems, P. J., Baselmans, D., Berger, C. P.A.M., Berrens, A., Bickerstaffe, H., Bos, S. D., Braam, M., Buddingh, K. T., Claus, S., Dekker, K., van Doeveren, T., Einerhand, S.M.H., Fossion, L. M.C.L., van Gennep, E. J., van Ginkel, N., Palacios, LA Grondhuis, Hermans, T. J.N., Hobijn, M. M., van Huystee, S. H., Jaspers-Valentijn, M., Klaver, O.S., Koldewijn, E. L., Korsten, L., Lenting, A., Lentjes, K. J., Luiting, H. B., van der Meer, S., Nieuwenhuijzen, J. A., Noordzij, M. A., Nooter, R. I., Notenboom, C. A.W., Oomen, R. J.A., van Roermund, J. G.H., de Rooij, J., Roshani, H., Schrier, B. P., van der Slot, M. A., Somford, D. M., Stelwagen, P. J., Stroux, A. M.A., van der West, A., Wijsman, B. P., and van Beek, Sytse C.

Abstract

Background: Radical cystectomy with pelvic lymph node dissection is the recommended treatment in non-metastatic muscle-invasive bladder cancer (MIBC). In randomised trials, robot-assisted radical cystectomy (RARC) showed non-inferior short-term oncological outcomes compared with open radical cystectomy (ORC). Data on intermediate and long-term oncological outcomes of RARC are limited. Objective: To assess the intermediate-term overall survival (OS) and recurrence-free survival (RFS) of patients with MIBC and high-risk non-MIBC (NMIBC) who underwent ORC versus RARC in clinical practice. Methods and materials: A nationwide retrospective study in 19 Dutch hospitals including patients with MIBC and high-risk NMIBC treated by ORC (n = 1086) or RARC (n = 386) between January 1, 2012 and December 31, 2015. Primary and secondary outcome measures were median OS and RFS, respectively. Survival outcomes were estimated using Kaplan-Meier curves. A multivariable Cox regression model was developed to adjust for possible confounders and to assess prognostic factors for survival including clinical variables, clinical and pathological disease stage, neoadjuvant therapy and surgical margin status. Results: The median follow-up was 5.1 years (95% confidence interval ([95%CI] 5.0–5.2). The median OS after ORC was 5.0 years (95%CI 4.3–5.6) versus 5.8 years after RARC (95%CI 5.1–6.5). The median RFS was 3.8 years (95%CI 3.1–4.5) after ORC versus 5.0 years after RARC (95%CI 3.9–6.0). After multivariable adjustment, the hazard ratio for OS was 1.00 (95%CI 0.84–1.20) and for RFS 1.08 (95%CI 0.91–1.27) of ORC versus RARC. Patients who underwent ORC were older, had higher preoperative serum creatinine levels and more advanced clinical and pathological disease stage. Conclusion: ORC and RARC resulted in similar intermediate-term OS and RFS in a cohort of almost 1500 MIBC and high-risk NMIBC.

Published
2022

10. Intermediate-term overall survival of robot-assisted versus open radical cystectomy for muscle-invasive and high-risk non muscle-invasive bladder cancer in the Netherlands

Author

Hinsenveld, F.J., primary, Boormans, J.L., additional, Van Der Poel, H.G., additional, Van Der Schoot, D.K.E., additional, Vis, A.N., additional, Aben, K.K.H., additional, Arends, T., additional, De Rooij, J., additional, Windt, W.A.K.M., additional, Buddingh, K.T., additional, Claus, S., additional, Dekker, K., additional, Grondhuis Palacios, L.A., additional, Hermans, T.J.N., additional, Van Huystee, S., additional, Jaspers-Valentijn, M., additional, Lenting, A., additional, Lentjes, K.J., additional, Oomen, R.J.A., additional, Van Der Slot, M.A., additional, Stelwagen, P.J., additional, Van Der West, A., additional, and Van Beek, S.C., additional

Published
2021
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11. 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

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. Compérat, 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. 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.C. 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.V. Valdagni, R. Van Der Heijden, A.G. Van Poppel, H. Vartolomei, M.D. Veskimäe, E. Vilaseca, A. Rivera, F.A.V. Wiegel, T. Wiklund, P. Willemse, P.-P.M. Williams, A. Zigeuner, R. Horwich, A.

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 © 2019 European Society of Medical Oncology and European Association of Urology

Published
2020

12. 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

Author

Witjes JA, 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, Der Kwast TV, 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, De Blok W, J L De Visschere P, 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, Mir MC, Moschini M, Mostafid H, Müller AC, Müller CR, N'Dow J, Necchi A, Neuzillet Y, Oddens JR, Oldenburg J, Osanto S, J G Oyen W, 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, Lauridsen SV, Valdagni R, Van Der Heijden AG, Van Poppel H, Vartolomei MD, Veskimäe E, Vilaseca A, Rivera FAV, Wiegel T, Wiklund P, Williams A, Zigeuner R, Horwich A.

Subjects
Consensus, Follow-up, education, Bladder cancer, Diagnosis, Treatment, Delphi
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 prior to 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), and 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 statements, 33 (28%) achieved level 1 consensus and 49 (42%) 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 when further evidence is available to guide our approach. Patient summary: This report summarises findings from an international, multistakeholder project organised by the EAU and ESMO. In this project, a steering committee identified areas of bladder cancer management where there is currently no good-quality evidence to guide treatment decisions. From this, they developed a series of proposed statements, 71 of which achieved consensus by a large group of experts in the field of bladder cancer. It is anticipated that these statements will provide further guidance to health care professionals and could help improve patient outcomes until a time when good-quality evidence is available.

Published
2020

13. SRPK3 regulates alternative pre-mRNA splicing required for B lymphocyte development and humoral responsiveness

Author

Raul M. Torres, Knapp, Taliaferro Jm, Hagman, Eric Peterman, Arends T, and Brian P. O'Connor

Subjects
0303 health sciences, Lymphocyte, Alternative splicing, Biology, 3. Good health, Cell biology, 03 medical and health sciences, 0302 clinical medicine, SR protein, medicine.anatomical_structure, Antigen, RNA splicing, Conditional gene knockout, Transcriptional regulation, medicine, B cell, 030304 developmental biology, 030215 immunology
Abstract

Alternative splicing (AS) of pre-mRNA is a critical component of transcriptional regulation that diversifies the cellular proteome. The Serine-Arginine Protein Kinases (SRPK) initiate early events in AS. Using conditional knockout mice (cKO), we demonstrated the importance of the X-linked gene Srpk3 in B lymphocyte development and in response to immunization in vivo. Significantly decreased numbers of immature and mature B cells were observed in Srpk3-cKO BM relative to wild-type (WT). Immunization of Srpk3-cKO mice with a T lymphocyte-independent type-2 antigen elicited greatly reduced amounts of specific IgG3. Srpk3 deletion resulted in hundreds of differentially spliced mRNAs in B cells, including mRNAs encoding proteins associated with signaling pathways and mitochondrial function. Several alternative splicing outcomes in Srpk3-cKO cells are due to altered splicing regulation of SR proteins. We conclude that Srpk3 is an immunomodulatory kinase that controls humoral immunity via its regulation of pre-mRNA splicing, antibody production, and metabolism in B cells.One Sentence SummarySRPK3 regulates alternative splicing of pre-mRNA that is crucial for B cell development, activation and antibody responses.

Published
2019
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14. The frequency dependence of hygro-expansive scaling of oak

Author

Arends, T., Pel, L., Smeulders, D.M.J., Arends, T., Pel, L., and Smeulders, D.M.J.

Abstract

Fluctuations in the ambient relative humidity are often cyclic of nature, composed of a wide variety of frequencies. Variations may be as fast as one minute or as slow as a complete season. A wooden object exposed to these fluctuations exchanges moisture with the air, resulting in a change in the local moisture content of the wood. Since moisture penetration is affected by the timescale of the changes in ambient conditions, so are processes caused by moisture content variations. Moisture content variations cause dimensional changes of a wooden object, which, if mechanically restrained, lead to a buildup of stresses and ultimately to damage. It is therefore important to predict the frequency behavior of moisture content and expansion in wood. In the presented study, experiments are conducted in which the moisture content and expansion of oak cubes with different sizes is measured during sinusoidal relative humidity fluctuations with different frequencies. The amplitude in moisture content and expansion is shown to be simply scalable based on sample size only. Derived diffusion coefficients are in agreement with literature values, although the experimental frequency behavior is shown to deviate qualitatively from diffusive frequency behavior.

Published
2020

15. 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

Author

Witjes, JA, 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, Comperat, E, Crabb, S, Culine, S, De Bari, B, De Blok, 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, Grubmueller, 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-Espinos, E, Logager, V, Lorch, A, Loriot, Y, Meijer, R, Mir, MC, Moschini, M, Mostafid, H, Mueller, A-C, Mueller, CR, N'Dow, J, Necchi, A, Neuzillet, Y, Oddens, JR, Oldenburg, J, Osanto, S, Oyen, WJG, Pacheco-Figueiredo, L, Pappot, H, Patel, M, Pieters, BR, Plass, K, Remzi, M, Retz, M, Richenberg, J, Rink, M, Roghmann, F, Rosenberg, JE, Roupret, M, Rouviere, O, Salembier, C, Salminen, A, Sargos, P, Sengupta, S, Sherif, A, Smeenk, RJ, Smits, A, Stenzl, A, Thalmann, GN, Tombal, B, Turkbey, B, Lauridsen, SV, Valdagni, R, Van der Heijden, AG, Van Poppel, H, Vartolomei, MD, Veskimae, E, Vilaseca, A, Rivera, FAV, Wiegel, T, Wiklund, P, Williams, A, Zigeuner, R, Horwich, A, Witjes, JA, 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, Comperat, E, Crabb, S, Culine, S, De Bari, B, De Blok, 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, Grubmueller, 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-Espinos, E, Logager, V, Lorch, A, Loriot, Y, Meijer, R, Mir, MC, Moschini, M, Mostafid, H, Mueller, A-C, Mueller, CR, N'Dow, J, Necchi, A, Neuzillet, Y, Oddens, JR, Oldenburg, J, Osanto, S, Oyen, WJG, Pacheco-Figueiredo, L, Pappot, H, Patel, M, Pieters, BR, Plass, K, Remzi, M, Retz, M, Richenberg, J, Rink, M, Roghmann, F, Rosenberg, JE, Roupret, M, Rouviere, O, Salembier, C, Salminen, A, Sargos, P, Sengupta, S, Sherif, A, Smeenk, RJ, Smits, A, Stenzl, A, Thalmann, GN, Tombal, B, Turkbey, B, Lauridsen, SV, Valdagni, R, Van der Heijden, AG, Van Poppel, H, Vartolomei, MD, Veskimae, E, Vilaseca, A, Rivera, FAV, Wiegel, T, Wiklund, P, Williams, A, Zigeuner, R, and Horwich, 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 prior to 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), and 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 statements, 33 (28%) achieved level 1 consensus and 49 (42%) 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 stateme

Published
2020

16. 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. 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. Compérat, E. Crabb, S. Culine, S. De Bari, B. DeBlok, 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. 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. Carmen Mir, M. 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. Vahr Lauridsen, S. Valdagni, R. Van Der Heijden, A.G. Van Poppel, H. Vartolomei, M.D. Veskimäe, E. Vilaseca, A. Vives Rivera, F.A. Wiegel, T. Wiklund, P. Williams, A. Zigeuner, R. Witjes, J.A.

Subjects
education
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. © 2019 European Society for Medical Oncology

Published
2019

17. 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
Full Text
View/download PDF

18. 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

19. Dynamics of heterogeneous crosslinking in room temperature vulcanizing poly(dimethyl siloxane) and its dependence on moisture supply

Author

Arends, T., Huinink, H.P., Pel, L., Arends, T., Huinink, H.P., and Pel, L.

Abstract

The influence of moisture supply on the crosslinking rate in room temperature vulcanizing poly(dimethyl siloxane) is investigated using spatially resolved 1H nuclear magnetic resonance relaxometry. Using this technique, we observe heterogeneous crosslinking manifested in a front moving into the material from the exposed surface, which separates the crosslinked and uncrosslinked parts of the material. The presence of a sharp boundary indicates that moisture transport towards the front is the limiting factor in the crosslinking process. As a result, the moisture supply controls the crosslinking front velocity, which we capture in a diffusion-reaction model. Reasonable agreement is found between the front diffusivity retrieved directly from nuclear magnetic resonance experiments and calculated values using independently measured properties of the crosslinked silicone rubber. This result demonstrates the direct relationship between exposure moisture content, moisture diffusion, and crosslink density on the crosslinking front dynamics in room temperature vulcanizing poly(dimethyl siloxane).

Published
2019

20. 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

21. 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

22. P0823 - Intermediate-term overall survival of robot-assisted versus open radical cystectomy for muscle-invasive and high-risk non muscle-invasive bladder cancer in the Netherlands

Author

Hinsenveld, F.J., Boormans, J.L., Van Der Poel, H.G., Van Der Schoot, D.K.E., Vis, A.N., Aben, K.K.H., Arends, T., De Rooij, J., Windt, W.A.K.M., Buddingh, K.T., Claus, S., Dekker, K., Grondhuis Palacios, L.A., Hermans, T.J.N., Van Huystee, S., Jaspers-Valentijn, M., Lenting, A., Lentjes, K.J., Oomen, R.J.A., Van Der Slot, M.A., Stelwagen, P.J., Van Der West, A., and Van Beek, S.C.

Published
2021
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24. Moisture transport in pine wood during one-sided heating studied by NMR

Author

Arends, T., Barakat, A.J., Pel, L., Arends, T., Barakat, A.J., and Pel, L.

Abstract

The quantification of moisture transport in heated wood is relevant to several fields, e.g. for lumber drying and processing and for fire safety risk assessment. We present non-destructive and simultaneous measurements of the moisture content and temperature distributions in pine wood during unilateral exposure to a heat source. The moisture content is measured by a nuclear magnetic resonance setup specifically built for the evaluation of moisture transport in porous materials at elevated temperatures. Temperature profiles are obtained by thermocouples placed at different distances from the exposed surface. While the temperature rises, a peak in the moisture content is formed, which travels towards the unexposed surface. The velocity of the moisture content peak depends on the principal direction in which transport occurs, as confirmed by experiments. Numerical simulations of moisture transport are performed which can qualitatively reproduce the behavior observed in experiments. Moreover, several characteristics, such as the timescale and non-linearity of the moisture peak position, are well captured. The influence of several input parameters, such as the permeability and diffusion coefficient, on the moisture peak dynamics is elaborately explored.

Published
2018

25. Moisture penetration in oak during sinusoidal humidity fluctuations studied by NMR

Author

Arends, T., Pel, Leo, Smeulders, D.M.J., Arends, T., Pel, Leo, and Smeulders, D.M.J.

Abstract

Most natural fluctuations in relative humidity are cyclic of nature, e.g. daily or seasonal. During these fluctuations, hygroscopic materials exchange moisture with the surrounding air. The penetration of moisture into the material depends on the frequency of the fluctuation, but also on the transport characteristics of the material. Here we present an experimental study on the penetration depth of moisture in oak during sinusoidal relative humidity fluctuations, covering a wide range of frequencies. Using nuclear magnetic resonance, we show that the amplitude in moisture content decreases exponentially from the exposed surface. The slope of the decay on a logarithmic scale provides the diffusion coefficient in the three principal directions of wood (longitudinal, radial, tangential), which are in good agreement with literature values. Furthermore, we show the influence of the moisture content range on the decay in amplitude by performing experiments in different relative humidity ranges. Numerical experiments are performed to assess the dependence of moisture penetration on different model parameters.

Published
2018

26. Fluids in porous media: Transport and phase changes

Author

Huinink, H.P., Ruijten, P., Arends, T., Transport in Permeable Media, Energy Technology, and Thermo-Chemical Materials Lab

Abstract

This book introduces the reader into the field of the physics of processes occurring in porous media. It targets Master and PhD students who need to gain fundamental understanding the impact of confinement on transport and phase change processes. The book gives brief overviews of topics like thermodynamics, capillarity and fluid mechanics in order to launch the reader smoothly into the realm of porous media. In-depth discussions are given of phase change phenomena in porous media, single phase flow, unsaturated flow and multiphase flow. In order to make the topics concrete the book contains numerous example calculations. Further, as much experimental data as possible is plugged in to give the reader the ability to quantify phenomena.

Published
2016

29. 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

30. DUX4-induced HSATII RNA accumulation drives protein aggregation impacting RNA processing pathways.

Author

Arends T, Bennett SR, and Tapscott SJ

Abstract

RNA-driven protein aggregation leads to cellular dysregulation by sequestering regulatory proteins, disrupting normal cellular processes, and contributing to the development of diseases and tumorigenesis. Here, we show that double homeobox 4 (DUX4), an early embryonic transcription factor and causative gene of facioscapulohumeral muscular dystrophy (FSHD), induces the accumulation of stable intranuclear RNAs, including nucleolar-associated RNA and human satellite II (HSATII) repeat RNA. Stable intranuclear RNAs drive protein aggregation in DUX4-expressing muscle cells. Specifically, HSATII RNA sequesters m 6 A and m 5 C RNA methylation factors. Furthermore, HSATII-YBX1 ribonucleoprotein (RNP) complex formation is mediated by HSATII RNA accumulation, NSUN2 activity and RNA methylation. YBX-1 specifically associates with HSATII double-stranded RNA. Aberrant HSATII-RNP complexes affect key RNA processing pathways, including mRNA splicing. Differential splicing of genes mediated by HSATII-RNP complexes are associated with pathways known to be dysregulated by DUX4 expression. These findings highlight the broader influence of DUX4 on nuclear RNA dynamics and suggest that HSATII RNA could be a critical mediator of RNA processing regulation in DUX4-expressing cells. Understanding the impact of HSATII-RNP formation on RNA processing pathways provides valuable insight into the molecular mechanisms underlying FSHD., Competing Interests: COMPETING INTERESTS The authors declare no competing financial interests.

Published
2024
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31. Facioscapulohumeral Dystrophy: Molecular Basis and Therapeutic Opportunities.

Author

Arends T, Hamm DC, van der Maarel S, and Tapscott SJ

Abstract

Facioscapulohumeral dystrophy (FSHD) is caused by misexpression of the early embryonic transcription factor Double Homeobox Protein 4 (DUX4) in skeletal muscle. DUX4 is normally expressed at the 4-cell stage of the human embryo and initiates a portion of the first wave of embryonic gene expression that establishes the totipotent cells of the embryo. Following brief expression, the DUX4 locus is suppressed by epigenetic silencing and remains silenced in nearly all somatic cells. Mutations that cause FSHD decrease the efficiency of epigenetic silencing of the DUX4 locus and result in aberrant expression of this transcription factor in skeletal muscles. DUX4 expression in these skeletal muscles reactivates part of the early totipotent program and suppresses the muscle program-resulting in a progressive muscular dystrophy that affects some muscles earlier than others. These advances in understanding the cause of FSHD have led to multiple therapeutic strategies that are now entering clinical trials., (Copyright © 2024 Cold Spring Harbor Laboratory Press; all rights reserved.)

Published
2024
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32. DUX4-induced HSATII transcription causes KDM2A/B-PRC1 nuclear foci and impairs DNA damage response.

Author

Arends T, Tsuchida H, Adeyemi RO, and Tapscott SJ

Subjects
Cell Nucleus genetics, Epigenomics, Histones genetics, Humans, F-Box Proteins metabolism, Jumonji Domain-Containing Histone Demethylases metabolism, Cell Cycle Proteins metabolism, DNA Repair, Homeodomain Proteins metabolism, Multiprotein Complexes metabolism
Abstract

Polycomb repressive complexes regulate developmental gene programs, promote DNA damage repair, and mediate pericentromeric satellite repeat repression. Expression of pericentromeric satellite repeats has been implicated in several cancers and diseases, including facioscapulohumeral dystrophy (FSHD). Here, we show that DUX4-mediated transcription of HSATII regions causes nuclear foci formation of KDM2A/B-PRC1 complexes, resulting in a global loss of PRC1-mediated monoubiquitination of histone H2A. Loss of PRC1-ubiquitin signaling severely impacts DNA damage response. Our data implicate DUX4-activation of HSATII and sequestration of KDM2A/B-PRC1 complexes as a mechanism of regulating epigenetic and DNA repair pathways., (© 2024 Arends et al.)

Published
2024
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33. Intermediate-term survival of robot-assisted versus open radical cystectomy for muscle-invasive and high-risk non-muscle invasive bladder cancer in The Netherlands.

Author

Hinsenveld FJ, Boormans JL, van der Poel HG, van der Schoot DKE, Vis AN, Aben KKH, Arends TJ, Ausems PJ, Baselmans D, Berger C, Berrens A, Bickerstaffe H, Bos SD, Braam M, Buddingh KT, Claus S, Dekker K, van Doeveren T, Einerhand S, Fossion L, van Gennep EJ, van Ginkel N, Palacios G, Hermans T, Hobijn MM, van Huystee SH, Jaspers-Valentijn M, Klaver OS, Koldewijn EL, Korsten L, Lenting A, Lentjes KJ, Luiting HB, van der Meer S, Nieuwenhuijzen JA, Noordzij MA, Nooter RI, Notenboom C, Oomen R, van Roermund J, de Rooij J, Roshani H, Schrier BP, van der Slot MA, Somford DM, Stelwagen PJ, Stroux A, van der West A, Wijsman BP, Windt W, van Zanten P, and van Beek SC

Subjects
Aged, Female, Humans, Male, Netherlands, Retrospective Studies, Survival Analysis, Urinary Bladder Neoplasms mortality, Urinary Bladder Neoplasms pathology, Cystectomy methods, Robotic Surgical Procedures methods, Robotics methods, Urinary Bladder Neoplasms surgery
Abstract

Background: Radical cystectomy with pelvic lymph node dissection is the recommended treatment in non-metastatic muscle-invasive bladder cancer (MIBC). In randomised trials, robot-assisted radical cystectomy (RARC) showed non-inferior short-term oncological outcomes compared with open radical cystectomy (ORC). Data on intermediate and long-term oncological outcomes of RARC are limited., Objective: To assess the intermediate-term overall survival (OS) and recurrence-free survival (RFS) of patients with MIBC and high-risk non-MIBC (NMIBC) who underwent ORC versus RARC in clinical practice., Methods and Materials: A nationwide retrospective study in 19 Dutch hospitals including patients with MIBC and high-risk NMIBC treated by ORC (n = 1086) or RARC (n = 386) between January 1, 2012 and December 31, 2015. Primary and secondary outcome measures were median OS and RFS, respectively. Survival outcomes were estimated using Kaplan-Meier curves. A multivariable Cox regression model was developed to adjust for possible confounders and to assess prognostic factors for survival including clinical variables, clinical and pathological disease stage, neoadjuvant therapy and surgical margin status., Results: The median follow-up was 5.1 years (95% confidence interval ([95%CI] 5.0-5.2). The median OS after ORC was 5.0 years (95%CI 4.3-5.6) versus 5.8 years after RARC (95%CI 5.1-6.5). The median RFS was 3.8 years (95%CI 3.1-4.5) after ORC versus 5.0 years after RARC (95%CI 3.9-6.0). After multivariable adjustment, the hazard ratio for OS was 1.00 (95%CI 0.84-1.20) and for RFS 1.08 (95%CI 0.91-1.27) of ORC versus RARC. Patients who underwent ORC were older, had higher preoperative serum creatinine levels and more advanced clinical and pathological disease stage., Conclusion: ORC and RARC resulted in similar intermediate-term OS and RFS in a cohort of almost 1500 MIBC and high-risk NMIBC., Competing Interests: Conflict of interest All authors declare no conflicts of interest., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Published
2022
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34. Chromodomain helicase DNA-binding 4 (CHD4) regulates early B cell identity and V(D)J recombination.

Author

Hagman JR, Arends T, Laborda C, Knapp JR, Harmacek L, and O'Connor BP

Subjects
B-Lymphocytes metabolism, DNA, DNA Helicases genetics, DNA Helicases metabolism, Humans, Mi-2 Nucleosome Remodeling and Deacetylase Complex genetics, Mi-2 Nucleosome Remodeling and Deacetylase Complex metabolism, V(D)J Recombination
Abstract

B lymphocytes develop from uncommitted precursors into immunoglobulin (antibody)-producing B cells, a major arm of adaptive immunity. Progression of early progenitors to antibody-expressing cells in the bone marrow is orchestrated by the temporal regulation of different gene programs at discrete developmental stages. A major question concerns how B cells control the accessibility of these genes to transcription factors. Research has implicated nucleosome remodeling ATPases as mediators of chromatin accessibility. Here, we describe studies of chromodomain helicase DNA-binding 4 (CHD4; also known as Mi-2β) in early B cell development. CHD4 comprises multiple domains that function in nucleosome mobilization and histone binding. CHD4 is a key component of Nucleosome Remodeling and Deacetylase, or NuRD (Mi-2) complexes, which assemble with other proteins that mediate transcriptional repression. We review data demonstrating that CHD4 is necessary for B lineage identity: early B lineage progression, proliferation in response to interleukin-7, responses to DNA damage, and cell survival in vivo. CHD4-NuRD is also required for the Ig heavy-chain repertoire by promoting utilization of distal variable (V H ) gene segments in V(D)J recombination. In conclusion, the regulation of chromatin accessibility by CHD4 is essential for production of antibodies by B cells, which in turn mediate humoral immune responses to pathogens and disease., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Published
2022
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35. 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].

Author

Witjes JA, 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, De Blok 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, Mir MC, 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, Lauridsen SV, Valdagni R, Van Der Heijden AG, Van Poppel H, Vartolomei MD, Veskimäe E, Vilaseca A, Rivera FAV, Wiegel T, Wiklund P, Willemse PM, Williams A, Zigeuner R, and Horwich A

Published
2020
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36. CHD4 is essential for transcriptional repression and lineage progression in B lymphopoiesis.

Author

Arends T, Dege C, Bortnick A, Danhorn T, Knapp JR, Jia H, Harmacek L, Fleenor CJ, Straign D, Walton K, Leach SM, Feeney AJ, Murre C, O'Connor BP, and Hagman JR

Subjects
Animals, B-Lymphocytes cytology, Chromatin Assembly and Disassembly genetics, Gene Expression Regulation genetics, Mice, Mice, Transgenic, B-Lymphocytes metabolism, Cell Lineage genetics, DNA Helicases genetics, Lymphopoiesis genetics, Transcription, Genetic genetics
Abstract

Cell lineage specification is a tightly regulated process that is dependent on appropriate expression of lineage and developmental stage-specific transcriptional programs. Here, we show that Chromodomain Helicase DNA-binding protein 4 (CHD4), a major ATPase/helicase subunit of Nucleosome Remodeling and Deacetylase Complexes (NuRD) in lymphocytes, is essential for specification of the early B cell lineage transcriptional program. In the absence of CHD4 in B cell progenitors in vivo, development of these cells is arrested at an early pro-B-like stage that is unresponsive to IL-7 receptor signaling and unable to efficiently complete V(D)J rearrangements at Igh loci. Our studies confirm that chromatin accessibility and transcription of thousands of gene loci are controlled dynamically by CHD4 during early B cell development. Strikingly, CHD4-deficient pro-B cells express transcripts of many non-B cell lineage genes, including genes that are characteristic of other hematopoietic lineages, neuronal cells, and the CNS, lung, pancreas, and other cell types. We conclude that CHD4 inhibits inappropriate transcription in pro-B cells. Together, our data demonstrate the importance of CHD4 in establishing and maintaining an appropriate transcriptome in early B lymphopoiesis via chromatin accessibility., Competing Interests: The authors declare no conflict of interest., (Copyright © 2019 the Author(s). Published by PNAS.)

Published
2019
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37. Zinc Finger Protein 521 Regulates Early Hematopoiesis through Cell-Extrinsic Mechanisms in the Bone Marrow Microenvironment.

Author

Fleenor CJ, Arends T, Lei H, Åhsberg J, Okuyama K, Kuruvilla J, Cristobal S, Rabe JL, Pandey A, Danhorn T, Straign D, Espinosa JM, Warming S, Pietras EM, Sigvardsson M, and Hagman JR

Subjects
Animals, B-Lymphocytes cytology, B-Lymphocytes metabolism, Cytokines metabolism, Hematopoiesis genetics, Hematopoietic Stem Cells cytology, Lymphopoiesis genetics, Lymphopoiesis physiology, Mice, Mice, 129 Strain, Mice, Inbred C57BL, Mice, Knockout, Myelopoiesis genetics, Myelopoiesis physiology, Protein Binding, Stem Cell Niche genetics, T-Lymphocytes cytology, T-Lymphocytes metabolism, Transcription Factors deficiency, Transcription Factors genetics, Hematopoiesis physiology, Hematopoietic Stem Cells metabolism, Stem Cell Niche physiology, Transcription Factors metabolism
Abstract

Zinc finger protein 521 (ZFP521), a DNA-binding protein containing 30 Krüppel-like zinc fingers, has been implicated in the differentiation of multiple cell types, including hematopoietic stem and progenitor cells (HSPC) and B lymphocytes. Here, we report a novel role for ZFP521 in regulating the earliest stages of hematopoiesis and lymphoid cell development via a cell-extrinsic mechanism. Mice with inactivated Zfp521 genes ( Zfp521 ) possess reduced frequencies and numbers of hematopoietic stem and progenitor cells, common lymphoid progenitors, and B and T cell precursors. Notably, ZFP521 deficiency changes bone marrow microenvironment cytokine levels and gene expression within resident HSPC, consistent with a skewing of hematopoiesis away from lymphopoiesis. These results advance our understanding of ZFP521's role in normal hematopoiesis, justifying further research to assess its potential as a target for cancer therapies.-/- ) possess reduced frequencies and numbers of hematopoietic stem and progenitor cells, common lymphoid progenitors, and B and T cell precursors. Notably, ZFP521 deficiency changes bone marrow microenvironment cytokine levels and gene expression within resident HSPC, consistent with a skewing of hematopoiesis away from lymphopoiesis. These results advance our understanding of ZFP521's role in normal hematopoiesis, justifying further research to assess its potential as a target for cancer therapies., (Copyright © 2018 American Society for Microbiology.)

Published
2018
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38. Germinal Center T Follicular Helper Cells Are Highly Permissive to HIV-1 and Alter Their Phenotype during Virus Replication.

Author

Kohler SL, Pham MN, Folkvord JM, Arends T, Miller SM, Miles B, Meditz AL, McCarter M, Levy DN, and Connick E

Subjects
Asymptomatic Diseases, Cell Differentiation, Cells, Cultured, HIV Infections virology, Host Specificity, Humans, Palatine Tonsil pathology, Phenotype, Programmed Cell Death 1 Receptor metabolism, Receptors, CXCR5 metabolism, Superinfection, T-Lymphocytes, Helper-Inducer virology, Virus Replication, Germinal Center immunology, HIV Infections immunology, HIV-1 physiology, T-Lymphocytes, Helper-Inducer immunology
Abstract

HIV-1 replication is concentrated within CD4(+) T cells in B cell follicles of secondary lymphoid tissues during asymptomatic disease. Limited data suggest that a subset of T follicular helper cells (TFH) within germinal centers (GC) is highly permissive to HIV-1. Whether GC TFH are the major HIV-1 virus-producing cells in vivo has not been established. In this study, we investigated TFH permissivity to HIV-1 ex vivo by spinoculating and culturing tonsil cells with HIV-1 GFP reporter viruses. Using flow cytometry, higher percentages of GC TFH (CXCR5(high)PD-1(high)) and CXCR5(+)programmed cell death-1 (PD-1)(low) cells were GFP(+) than non-GC TFH (CXCR5(+)PD-1(intermediate)) or extrafollicular (EF) (CXCR5(-)) cells. When sorted prior to spinoculation, however, GC TFH were substantially more permissive than CXCR5(+)PD-1(low) or EF cells, suggesting that many GC TFH transition to a CXCR5(+)PD-1(low) phenotype during productive infection. In situ hybridization on inguinal lymph node sections from untreated HIV-1-infected individuals without AIDS revealed higher frequencies of HIV-1 RNA(+) cells in GC than non-GC regions of follicle or EF regions. Superinfection of HIV-1-infected individuals' lymph node cells with GFP reporter virus confirmed the permissivity of follicular cells ex vivo. Lymph node immunostaining revealed 96% of CXCR5(+)CD4(+) cells were located in follicles. Within sorted lymph node cells from four HIV-infected individuals, CXCR5(+) subsets harbored 11-66-fold more HIV-1 RNA than CXCR5(-) subsets, as determined by RT PCR. Thus, GC TFH are highly permissive to HIV-1, but downregulate PD-1 and, to a lesser extent, CXCR5 during HIV-1 replication. These data further implicate GC TFH as the major HIV-1-producing cells in chronic asymptomatic HIV-1 infection., (Copyright © 2016 by The American Association of Immunologists, Inc.)

Published
2016
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39. Follicular regulatory T cells impair follicular T helper cells in HIV and SIV infection.

Author

Miles B, Miller SM, Folkvord JM, Kimball A, Chamanian M, Meditz AL, Arends T, McCarter MD, Levy DN, Rakasz EG, Skinner PJ, and Connick E

Subjects
Adult, Aged, Animals, Cells, Cultured, Chronic Disease, Female, Humans, Indoleamine-Pyrrole 2,3,-Dioxygenase metabolism, Macaca mulatta, Male, Middle Aged, Palatine Tonsil metabolism, Transforming Growth Factor beta metabolism, Young Adult, HIV Infections immunology, Lymph Nodes immunology, Simian Acquired Immunodeficiency Syndrome immunology, T-Lymphocytes, Helper-Inducer physiology, T-Lymphocytes, Regulatory physiology
Abstract

Human and simian immunodeficiency viruses (HIV and SIV) exploit follicular lymphoid regions by establishing high levels of viral replication and dysregulating humoral immunity. Follicular regulatory T cells (TFR) are a recently characterized subset of lymphocytes that influence the germinal centre response through interactions with follicular helper T cells (TFH). Here, utilizing both human and rhesus macaque models, we show the impact of HIV and SIV infection on TFR number and function. We find that TFR proportionately and numerically expand during infection through mechanisms involving viral entry and replication, TGF-β signalling, low apoptosis rates and the presence of regulatory dendritic cells. Further, TFR exhibit elevated regulatory phenotypes and impair TFH functions during HIV infection. Thus, TFR contribute to inefficient germinal centre responses and inhibit HIV and SIV clearance.

Published
2015
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