The significance of the expression of dihydropyrimidine dehydrogenase in prostate cancer.

OBJECTIVE: To measure dihydropyrimidine dehydrogenase (DPD), an enzyme involved in the metabolism of 5-fluorouracil (5-FU), expression in prostate cancer and determine whether 5-chloro-2,4-dihydroxypyridine (CDHP), a potent inhibitor of DPD, enhances the antitumoral activity of 5-FU against prostate cancer. PATIENTS, MATERIALS AND METHODS: In all, 44 prostate tissue specimens were obtained from men who had a radical prostatectomy alone for prostate cancer, and 38 specimens from men who had had neoadjuvant hormonal therapy. We analysed the cancerous tissue and normal prostate tissue for DPD expression using immunohistochemistry, and determined its prognostic significance. In cultured human prostate cancer lines (DU145 and LNCaP), we compared the cytotoxicity of 5-FU/CDHP with that of 5-FU alone. Finally, in experiments on immunodeficient mice, we studied the effect of oral administration of tegafur, a pro-drug for 5-FU, with or without CDHP on the growth of tumours introduced by injection of DU145 cells. RESULTS: The expression of DPD was significantly higher in cancerous than normal prostate tissue; 36 of 44 (82%) specimens of prostate cancer expressed DPD, whereas only 25 of 44 (57%) specimens of normal prostate tissue expressed DPD. For men with prostate cancer who had radical prostatectomy alone, men with negative DPD expression tended to have a longer recurrence-free survival than those with positive expression; there were no recurrences in men with prostate cancer and negative DPD expression in the 5-year follow-up. DPD expression was significantly lower in men with prostate cancer who received neoadjuvant hormonal therapy. In vitro treatment of human prostate cancer cell lines with 5-FU/CDHP showed more cytotoxicity than with 5-FU treatment alone. Finally, DU145 tumours in mice treated with tegafur and CDHP were significantly smaller than in mice given tegafur alone. CONCLUSION: The present study showed that DPD expression is elevated in prostate cancer, and indicate that DPD inhibitors might enhance the antitumour activity of 5-FU against prostate cancer.

Significance of electrostimulation in detecting neurovascular bundle during radical prostatectomy.

OBJECTIVE: The reported rate of erectile dysfunction after nerve-sparing prostatectomy varies according to physicians. Because exact preservation of the neurovascular bundle (NVB) solely depends on the judgment of the physician, he or she should try to correctly identify the NVB and also avoid neurophysiologic injury of the NVB during the procedure. The purpose of the present study is to assess the status of the NVB preservation by physician's judgment at the operation, the changes in intracavernous pressure related to intraoperative electrical stimulation and postoperative histopathological examination. PATIENTS AND METHODS: Thirty-eight patients who underwent nerve-sparing radical prostatectomy judged by intraoperative electrical stimulation of the NVB were included in this study. Bilateral, unilateral and non-nerve-sparing procedures were performed in 18, 17, and 3 cases, respectively. The NVB preservation evaluated by intraoperative physician's judgment was compared to that evaluated by postoperative histopathological examination. Furthermore, the NVB preservation evaluated by intraoperative electrical stimulation was compared to that by physician's judgment and postoperative histopathological examination. RESULTS: For 68 of 76 NVB (89.5%), intraoperative subjective judgment and histopathological assessment were identical. For 66 of 76 NVB (86.8%), electrical stimulation findings and the physician's judgments were identical, and for 70 of 76 NVB (92.1%), electrical stimulation findings and histopathological findings were identical. CONCLUSION: Even if physicians are convinced of a successful nerve-sparing procedure, there are some cases in which the NVB is not preserved accurately or neurophysiological damage is suffered. Therefore, intraoperative electrical stimulation of the NVB as well as the cavernosal nerve is very useful in evaluation of NVB preservation.