Original Article

Cancer Chemotherapy and Pharmacology

, Volume 59, Issue 5, pp 643-650

First online:

Histological changes in bladders of patients submitted to ifosfamide chemotherapy even with mesna prophylaxis

  • Marcos Venício Alves LimaAffiliated withDepartment of Surgery, Division of Urology, Cancer Institute of Ceará
  • , Francisco Valdeci FerreiraAffiliated withDepartment of Pathology, Cancer Institute of Ceará
  • , Francisco Yuri Bulcão MacedoAffiliated withDepartment of Physiology and Pharmacology, Faculty of Medicine, Universidade Federal do Ceará
  • , Gerly Anne de Castro BritoAffiliated withDepartment of Morphology, Faculty of Medicine, Universidade Federal do Ceará
  • , Ronaldo Albuquerque RibeiroAffiliated withDepartment of Physiology and Pharmacology, Faculty of Medicine, Universidade Federal do CearáDepartment of Clinical Oncology, Cancer Institute of CearáCentro de Biomedicina, Faculdade de Medicina, Universidade Federal do Ceará Email author 

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Hemorrhagic cystitis (HC) is a limiting side effect of chemotherapy with ifosfamide (IFS). Mesna is the drug of choice for prevention of HC. In this study, we analyzed cystoscopic and histological changes present in bladders of patients using IFS with mesna prophylaxis.


Thirty-three patients selected for IFS plus three doses of mesna chemotherapy regime were assigned at random to two groups: Group I or reference group consisted of 18 patients yet untreated. Group II consisted of 15 patients in whom urinalysis and cystoscopy plus vesical biopsy were performed only 24 h after receiving the last dose of IFS. The cystoscopic and histological findings were used as parameters for evaluating the results. For the former the criterion adopted was macroscopic vesical changes in accordance with Gray’s criteria. Histological analyses were performed by evaluation method especially adapted to this study.


Even under treatment with three doses of mesna, 66.7% of patients presented cystoscopic alterations and 100% showed bladder mucosa microscopic alterations such as edema, exocytosis, and hemorrhage.


The standard protocol used for prevention of IFS-induced HC with three doses of mesna does not completely prevent bladder damage. The histopathological criteria used in this study for observation of inflammatory events allowed staging the intensity of IFS-induced urothelial and mucosal injury.


Ifosfamide Hemorrhagic cystitis Mesna Histopathology