Histological changes in bladders of patients submitted to ifosfamide chemotherapy even with mesna prophylaxis
- First Online:
- 174 Downloads
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.
KeywordsIfosfamide Hemorrhagic cystitis Mesna Histopathology
- 11.Hu VY, Malley S, Dattilio A, Folsom SB, Zvara P, Vizzard MA (2003) COX-2 and prostanoid expression in micturition pathways after cyclophosphamide-induced cystitis in the rat. Am J Physiol Regul Integr Comp Physiol 284:574–585Google Scholar
- 12.Gray KJ, Engelmann UH, Johnson EH, Fishman IJ (1986) Evaluation of misoprostol cytoprotection of the bladder with cyclophosphamide (Cytoxan) therapy. J Urol 133:497–500Google Scholar
- 13.Katz A, Epelman S, Anelli A et al (1995) A prospective randomized evaluation of three schedules of mesna administration in patients receiving an ifosfamide-containing chemotherapy regimen: sustained efficiency and simplified administration. J Cancer Res Clin Oncol 121:128–131PubMedCrossRefGoogle Scholar
- 18.Ribeiro RA, Freitas HC, Campos MC et al (2002) Tumor necrosis factor-α and interleukin-1β mediate the production of nitric oxide involved in the pathogenesis of ifosfamide induced hemorrhagic cystitis in mice. J Urol 150:2229–2234Google Scholar
- 19.Shepherd JD, Pringle LE, Barnett MJ, Klingemann HG, Reece DE, Phillips GL (1991) Mesna versus hyperhydration for the prevention of cyclophosphamide-induced hemorrhagic cystitis in bone marrow transplantation. J Clin Oncol 11:2016–2020Google Scholar
- 20.Souza-Filho MVP, Lima MVA, Pompeu MML, Ballejo G, Cunha FQ, Ribeiro RA (1997) Involvement of nitric oxide in the pathogenesis of cyclophosphamide-induced hemorrhagic cystitis. Am J Pathol 150:247–256Google Scholar