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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Lima
Marcos Venício Alves
MV
Department of Surgery, Division of Urology, Cancer Institute of Ceará, Fortaleza, Brazil.
Ferreira
Francisco Valdeci
FV
Macedo
Francisco Yuri Bulcão
FY
de Castro Brito
Gerly Anne
GA
Ribeiro
Ronaldo Albuquerque
RA
D000293:Adolescent; D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects* / Q000627:therapeutic use; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use; D003558:Cystoscopy; D004487:Edema / Q000139:chemically induced / Q000473:pathology; D004912:Erythrocytes / Q000187:drug effects; D005047:Etoposide / Q000627:therapeutic use; D005089:Exocytosis / Q000187:drug effects; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced / Q000473:pathology; D006801:Humans; D007069:Ifosfamide / Q000009:adverse effects* / Q000627:therapeutic use; D008297:Male; D015080:Mesna / Q000627:therapeutic use*; D008875:Middle Aged; D001743:Urinary Bladder / Q000473:pathology*; D001745:Urinary Bladder Diseases / Q000139:chemically induced* / Q000473:pathology*; D019459:Urothelium / Q000473:pathology
D018906:Antineoplastic Agents, Alkylating; D000972:Antineoplastic Agents, Phytogenic; D005047:Etoposide; D015080:Mesna; D007069:Ifosfamide