Tom J H Arends1, Johannes Falke2, Rianne J M Lammers3, Diederik M Somford4, Jan C M Hendriks5, Mirjam C A de Weijert6, Harm C Arentsen7, Antoine G van der Heijden8, Egbert Oosterwijk9, J Alfred Witjes10. 1. Department of Urology, Radboud University Medical Centre, Geert Grooteplein zuid 10, 6525 GA, Nijmegen, The Netherlands. Tom.arends@radboudumc.nl. 2. Department of Urology, Radboud University Medical Centre, Geert Grooteplein zuid 10, 6525 GA, Nijmegen, The Netherlands. josfalke@gmail.com. 3. Department of Urology, Radboud University Medical Centre, Geert Grooteplein zuid 10, 6525 GA, Nijmegen, The Netherlands. Rianne_lammers@hotmail.com. 4. Canisius Wilhelmina Ziekenhuis, Weg door Jonkerbos 100, 6532 SZ, Nijmegen, The Netherlands. r.somford@cwz.nl. 5. Biostatistician, Department for Health Evidence, Radboud University Medical Centre, Geert Grooteplein zuid 10, 6525 GA, Nijmegen, The Netherlands. Jan.cm.hendriks@radboudumc.nl. 6. Department of Urology, Radboud University Medical Centre, Geert Grooteplein zuid 10, 6525 GA, Nijmegen, The Netherlands. Mirjam.deweijert@radboudumc.nl. 7. Department of Urology, Radboud University Medical Centre, Geert Grooteplein zuid 10, 6525 GA, Nijmegen, The Netherlands. Harm.arentsen@radboudumc.nl. 8. Department of Urology, Radboud University Medical Centre, Geert Grooteplein zuid 10, 6525 GA, Nijmegen, The Netherlands. toine.vanderheijden@radboudumc.nl. 9. Department of Urology, Radboud University Medical Centre, Geert Grooteplein zuid 10, 6525 GA, Nijmegen, The Netherlands. Egbert.oosterwijk@radboudumc.nl. 10. Department of Urology, Radboud University Medical Centre, Geert Grooteplein zuid 10, 6525 GA, Nijmegen, The Netherlands. fred.witjes@radboudumc.nl.
Abstract
OBJECTIVES: To explore whether urinary cytokine and chemokine (CK) levels differed between cold mitomycin-C (cold-MMC)-treated patients and chemohyperthermia (C-HT)-treated patients, to shed light on the possible molecular mechanisms that might explain the superior outcome of C-HT. Furthermore, CK-differences were explored between C-HT responders and C-HT non-responders. METHODS: Twelve NMIBC patients were included. Nine received six-weekly C-HT, and three received four-weekly cold-MMC instillations. Urine was collected on 8-12 time points before and after every treatment. MDC, IL-2, IL-6, IL-8, IP-10, MCP-1 and RANTES were determined by Luminex(®)-analysis. RESULTS: Elevated urinary CK levels were observed in both groups after treatment. In general, CK-peaks were lower in the cold-MMC group in comparison with levels in the C-HT group. Significant higher MCP-1 and IL-6 levels were observed in C-HT-treated patients. Additionally, significant cumulative effects were observed for IP-10 and IL-2. However, IP-10 and IL-2 levels did not significantly differ between treatments. MDC levels after the first week of treatment were significantly higher in the C-HT responders compared with the non-responders. CONCLUSION: MMC treatment leads to elevated urinary CK levels with significantly higher MCP-1 and IL-6 levels in C-HT-treated patients. Increased MDC levels after the first C-HT instillation appear to be related to good clinical outcome and might be of additional value to personalize treatment. Studies involving more patients and longer follow-up are needed to substantiate this observation.
OBJECTIVES: To explore whether urinary cytokine and chemokine (CK) levels differed between cold mitomycin-C (cold-MMC)-treated patients and chemohyperthermia (C-HT)-treated patients, to shed light on the possible molecular mechanisms that might explain the superior outcome of C-HT. Furthermore, CK-differences were explored between C-HT responders and C-HT non-responders. METHODS: Twelve NMIBC patients were included. Nine received six-weekly C-HT, and three received four-weekly cold-MMC instillations. Urine was collected on 8-12 time points before and after every treatment. MDC, IL-2, IL-6, IL-8, IP-10, MCP-1 and RANTES were determined by Luminex(®)-analysis. RESULTS: Elevated urinary CK levels were observed in both groups after treatment. In general, CK-peaks were lower in the cold-MMC group in comparison with levels in the C-HT group. Significant higher MCP-1 and IL-6 levels were observed in C-HT-treated patients. Additionally, significant cumulative effects were observed for IP-10 and IL-2. However, IP-10 and IL-2 levels did not significantly differ between treatments. MDC levels after the first week of treatment were significantly higher in the C-HT responders compared with the non-responders. CONCLUSION:MMC treatment leads to elevated urinary CK levels with significantly higher MCP-1 and IL-6 levels in C-HT-treated patients. Increased MDC levels after the first C-HT instillation appear to be related to good clinical outcome and might be of additional value to personalize treatment. Studies involving more patients and longer follow-up are needed to substantiate this observation.
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