Non-albicans Candida is the most common cause of candidemia in pediatric cancer patients.

GOALS: Candidemia is a serious infection that can severely complicate the care of children with cancer. We sought to determine the spectrum of Candida species in children with cancer, since effective therapy may depend on the species involved. PATIENTS AND METHODS: A retrospective review of candidemia episodes in our pediatric oncology patients over a 9-year period was conducted. During this period azole prophylaxis was not routine in this group. RESULTS: 38 episodes of candidemia were identified: C. albicans 29%, C. tropicalis 26%, C. parapsilosis 24%, C. krusei 8%, C. glabrata 8%, and C. lusitaniae 5%. Non-albicans Candida was common in patients not receiving azole prophylaxis. Species typically susceptible to azoles were common among patients not using azoles. Death attributed to the fungal infection occurred in 21% of episodes, with nearly all the deaths occurring in patients with C. albicans and C. tropicalis. CONCLUSIONS: C. albicans is not the predominant species in pediatric oncology patients experiencing candidemia, even in azole-naive patients.

Pharmacokinetics of etanidazole (SR-2508) in bladder and cervical cancer: evidence of diffusion from urine.

Following an IV infusion of 2.0 g/m2 of Etanidazole, the mean tumor concentration 40 min after injection was 126 micrograms/g in bladder cancer and 65 micrograms/g in cervical cancer. The tumor/plasma concentration ratio was 1.88 in bladder and 0.85 in cervical cancer. This high tumor concentration in bladder cancer could be accounted for by diffusion from a highly concentrated urine. This renders bladder cancer a suitable clinical model for testing this sensitizer.

Cell proliferation in carcinoma in bilharzial bladder: influence of pre-operative irradiation and clinical implications.

Cell proliferation in carcinoma in the bilharzial bladder was studied in 92 patients in terms of the in vitro labeling index (LI), cell density (CD) and labeled cell density (LCD) using the in vitro 3H-Tdr technique. Cell proliferation was much greater in high than in low grade tumors and in deep than in superficial parts of the tumor, but was much less dependent on cell type; transitional cell cancer had the highest activity followed by squamous cell and adenocarcinoma. The probability of local recurrence after cystectomy decreased markedly when the LI exceeded 5.0%. The influence of the following three pre-operative radiotherapy regimens was studied: split-course (SC): the initial course consisted of 20 Gy in 10 treatments with a similar course was given after one week, hyper-fractionation using 17 treatments 0.6 Gy each on two successive days, this 2-day course of 20 Gy was repeated after one week, and concentrated irradiation consisting of two treatments, 6.0 Gy each with a gap of one week. Cystectomy was performed 14-20 days after treatment in all groups. Preoperative irradiation was generally associated with an increased probability of local control. The unfavorable influence of a high pretreatment LI was not noted after pre-operative irradiation. The CD was also reduced in proportion to the pretreatment LI. It is proposed that the response to irradiation was proportional to the initial proliferation activity and hence the prognostic significance of tumor grade and pretreatment LI was masked. Postirradiation tumor volume reduction was a strong predictor of treatment outcome. Concentrated irradiation was the least efficient pre-operative irradiation regimen and was associated with the least tumor volume reduction.

The topical use of misonidazole in bladder cancer.

Penetration studies of MIS after intravesical administration showed adequate concentrations with a gradient across the tumor. After instillation of 2.5 g in 50 ml water the concentration in the deep parts of the tumor amounted to about 100 microgram per ml. This corresponds to a SER for hypoxic cell of the order of 1.7. A more uniform tissue distribution of the drug was noted 3.5 hours after an oral dose of 3 g/meter square. The concentration in the deep parts of the tumor and perivesical tissue was of the order of 100 micrograms/g. The concentration in these regions are relevant to preoperative irradiation which aims at sterilizing the deep infiltrating margins. The intravesical use with or without oral augmentation is suitable for use in association with concentrated preoperative radiotherapy regimens. The topical use of MIS in such regimens markedly reduces the risk of neurotoxicity. The tissue concentration resulting from the two routes proved to be additive. The higher concentration in lymph nodes after the oral route the greater concentration and prolonged contact after combined administration may have therapeutic merits.