title: Urinary cytokines in patients treated with intravesical mitomycin-C with and without hyperthermia.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Urology, Radboud University Medical Centre, Geert Grooteplein zuid 10, 6525 GA, Nijmegen, The Netherlands. Tom.arends@radboudumc.nl.
authors.forename: Tom J H
authors.initials: TJ
authors.lastname: Arends
authors.affiliation: Department of Urology, Radboud University Medical Centre, Geert Grooteplein zuid 10, 6525 GA, Nijmegen, The Netherlands. josfalke@gmail.com.
authors.forename: Johannes
authors.initials: J
authors.lastname: Falke
authors.affiliation: Department of Urology, Radboud University Medical Centre, Geert Grooteplein zuid 10, 6525 GA, Nijmegen, The Netherlands. Rianne_lammers@hotmail.com.
authors.forename: Rianne J M
authors.initials: RJ
authors.lastname: Lammers
authors.affiliation: Canisius Wilhelmina Ziekenhuis, Weg door Jonkerbos 100, 6532 SZ, Nijmegen, The Netherlands. r.somford@cwz.nl.
authors.forename: Diederik M
authors.initials: DM
authors.lastname: Somford
authors.affiliation: Biostatistician, Department for Health Evidence, Radboud University Medical Centre, Geert Grooteplein zuid 10, 6525 GA, Nijmegen, The Netherlands. Jan.cm.hendriks@radboudumc.nl.
authors.forename: Jan C M
authors.initials: JC
authors.lastname: Hendriks
authors.affiliation: Department of Urology, Radboud University Medical Centre, Geert Grooteplein zuid 10, 6525 GA, Nijmegen, The Netherlands. Mirjam.deweijert@radboudumc.nl.
authors.forename: Mirjam C A
authors.initials: MC
authors.lastname: de Weijert
authors.affiliation: Department of Urology, Radboud University Medical Centre, Geert Grooteplein zuid 10, 6525 GA, Nijmegen, The Netherlands. Harm.arentsen@radboudumc.nl.
authors.forename: Harm C
authors.initials: HC
authors.lastname: Arentsen
authors.affiliation: Department of Urology, Radboud University Medical Centre, Geert Grooteplein zuid 10, 6525 GA, Nijmegen, The Netherlands. toine.vanderheijden@radboudumc.nl.
authors.forename: Antoine G
authors.initials: AG
authors.lastname: van der Heijden
authors.affiliation: Department of Urology, Radboud University Medical Centre, Geert Grooteplein zuid 10, 6525 GA, Nijmegen, The Netherlands. Egbert.oosterwijk@radboudumc.nl.
authors.forename: Egbert
authors.initials: E
authors.lastname: Oosterwijk
authors.affiliation: Department of Urology, Radboud University Medical Centre, Geert Grooteplein zuid 10, 6525 GA, Nijmegen, The Netherlands. fred.witjes@radboudumc.nl.
authors.forename: J
authors.initials: J
authors.lastname: Alfred Witjes
mesh_terms: D000283:Administration, Intravesical; D000368:Aged; D000369:Aged, 80 and over; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage; D014408:Biomarkers, Tumor / Q000652:urine; D002295:Carcinoma, Transitional Cell / Q000473:pathology / Q000628:therapy*; D016207:Cytokines / Q000652:urine*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D006979:Hyperthermia, Induced / Q000379:methods*; D007322:Instillation, Drug; D008297:Male; D008875:Middle Aged; D016685:Mitomycin / Q000008:administration & dosage*; D012189:Retrospective Studies; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000473:pathology / Q000628:therapy*
chemical_list: D000903:Antibiotics, Antineoplastic; D014408:Biomarkers, Tumor; D016207:Cytokines; D016685:Mitomycin
keywords: Bladder cancer; Bladder instillation; Chemotherapy; Cytokines; Induced hyperthermia