Outcome predictors of high-energy transurethral microwave thermotherapy.

PURPOSE: Despite the good results of high-energy transurethral microwave thermotherapy (TUMT) for treatment of benign prostatic hyperplasia (BPH), it still is difficult to predict the response to treatment on an individual basis. In addition to clinical baseline parameters, histologic parameters seem to play a role in response variance after TUMT. High-energy TUMT has become widely accepted as a minimally invasive outpatient treatment in patients with lower urinary tract symptoms and BPH. Most patients benefit substantially from targeted microwave thermotherapy; however, little is known about optimal patient selection and the most relevant outcome parameters. MATERIALS AND METHODS: We evaluated Medline-based studies published between 1989 and 2000, including 900 patients suffering from lower urinary tract symptoms due to BPH who were undergoing TUMT. We evaluated outcome predictors for TUMT, such as histopathological parameters, prostate-specific antigen, and volume. RESULTS: Histologic and clinical outcome parameters were identified. Patient-to-patient differences in stromal-to-epithelial ratio of prostate tissue did affect outcomes. Poor responders to TUMT seemed to have a higher vessel density and a lower epithelial/stromal ratio. Relatively more abundant epithelial cells in the prostate tissue may lead to more favorable outcomes. Use of higher energy, patients with higher grade of obstruction, younger patient age, larger prostate volume (>25 mL), and higher prostate-specific antigen levels seemed to be associated with a better response to TUMT. CONCLUSIONS: New energy protocols could help tailor treatment to the individual needs of each patient. Nomograms based on volume, age, and pressure-flow parameters could assist in making clinical recommendations and identifying treatment responders; however, the total amount of energy appeared to have a high impact on the prediction of response.

The potentiated antileukemic effects of doxorubicin and interleukin-12 combination are not dependent on nitric oxide production.

In our recent study we described a significant antileukemic efficacy of a combination therapy with interleukin-12 (IL-12) and doxorubicin (DOX) in the L1210 leukemia model. This therapeutic effect was abrogated by elimination of activated macrophages. Activated macrophages produce a variety of factors that can contribute to the elimination of tumor cells in vivo, including proteases, TNF, reactive oxygen intermediates, and nitric oxide (NO). Based on the results of previous reports, the contribution of NO in potentiated antileukemic effects of IL-12 + DOX combination seemed to be highly possible. Both DOX and IL-12 given alone increased the production of NO by peritoneal macrophages, however, macrophages derived from the mice treated with the combination of those agents produced significantly less NO than macrophages from IL-12-alone-treated mice. Production of NO by spleen macrophages after IL-12 + DOX treatment was higher than it was in controls, IL-12-alone or DOX-alone-treated groups. In serum, concentrations of NOx- in IL-12- or IL-12 + DOX-treated mice were significantly higher in comparison with controls, however not significantly different from each other. Addition of L-NAME treatment to the IL-12 + DOX therapy in leukemia-bearing mice did not significantly change the antileukemic efficacy of this therapy. Thus, our results indicate that the augmented antileukemic effects of IL-12 + DOX combination therapy in L1210 model are NO-independent. Therefore, further studies on the possible mechanisms of potentiated antileukemic activity of combination of IL-12 and DOX would be worth pursuing.