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Efficacy of Urinary Mast Cell Mediators in Patients with Primary High-Grade Non-Muscle Invasive Bladder Cancer Treated with BCG Immunotherapy
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  • Muhammed Fatih Simsekoglu,
  • Islim Kaleler,
  • Cetin Demirdag,
  • Sinharib Citgez,
  • Ezel Uslu,
  • Ahmet Erozenci,
  • Zubeyr Talat
Muhammed Fatih Simsekoglu
Istanbul University-Cerrahpasa Cerrahpasa Faculty of Medicine
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Islim Kaleler
Istanbul University-Cerrahpasa Cerrahpasa Faculty of Medicine
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Cetin Demirdag
Istanbul University-Cerrahpasa Cerrahpasa Faculty of Medicine
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Sinharib Citgez
Istanbul University-Cerrahpasa Cerrahpasa Faculty of Medicine
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Ezel Uslu
Istanbul University-Cerrahpasa Cerrahpasa Faculty of Medicine
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Ahmet Erozenci
Istanbul University-Cerrahpasa Cerrahpasa Faculty of Medicine
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Zubeyr Talat
Istanbul University-Cerrahpasa Cerrahpasa Faculty of Medicine
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Abstract

Background: Mast cells play a critical role in tumor-associated immune pathways. We aimed to prospectively investigate the urinary mast cell mediators in patients with non-muscle invasive bladder cancer (NMIBC) treated with Bacillus Calmette-Guérin (BCG) immunotherapy. Methods: Nineteen patients who have received immunotherapy due to NMIBC and 19 healthy participants were enrolled. Urine samples were collected to assay N-methylhistamine, histamine and tryptase levels immediately before the first BCG instillation, immediately after the third and sixth instillations, and four weeks after the sixth instillation in patients with NMIBC and at a single visit in healthy participants. Cystoscopic examinations were performed on the patient with NMIBC at three-month intervals for two years. The changes in urinary markers due to BCC response, BCG instillation, and the presence of NMIBC were assessed. Results: The average age was 56.1 ± 10.5 years in patients with NMIBC. Fourteen patients had high-grade Ta tumors, and 5 had high-grade T1 tumors. While 12 patients responded, 6 presented with recurrence and 1 with progression. There was no correlation between the levels of mast cell mediators and BCG response. The N-methylhistamine and histamine levels were increased significantly with the onset of immunotherapy and N-methylhistamine levels were decreased significantly when immunotherapy was terminated. Pre-BCG estimated marginal means of N-methylhistamine were significantly higher in patients with NMIBC than healthy participants. Conclusions: This is the first study to determine that urine histamine and N-methylhistamine levels showing the change with immunotherapy. However, these mediators were not found to predict the patients’ response to immunotherapy.