Contribution of functional voltage-gated Na+ channel expression to cell behaviors involved in the metastatic cascade in rat prostate cancer: I. Lateral motility.

Previous work suggested that functional voltage-gated Na(+) channels (VGSCs) are expressed specifically in strongly metastatic cells of rat and human prostate cancer (PCa), thereby raising the possibility that VGSC activity could be involved in cellular behavior(s) related to the metastatic cascade. In the present study, the possible role of VGSCs in the lateral motility of rat PCa cells was investigated in vitro by testing the effect of modulators that either block or enhance VGSC activity. Two rat PCa cell lines of markedly different metastatic ability were used in a comparative approach: the strongly metastatic MAT-LyLu and the weakly metastatic AT-2 cell line, only the former being known to express functional VGSCs. Using both electrophysiological recording and a motility assay, the effects of two VGSC blockers (tetrodotoxin and phenytoin) and four potential openers (veratridine, aconitine, ATX II, and brevetoxin) were monitored on (a) Na(+) channel activity and (b) cell motility over 48 h. Tetrodotoxin (at 1 microM) and phenytoin (at 50 microM) both decreased the motility index of the MAT-LyLu cell line by 47 and 11%, respectively. Veratridine (at 20 microM) and brevetoxin (at 10 nM) had no effect on the motility of either cell line, whilst aconitine (at 100 microM) and ATX II (at 25 pM) significantly increased the motility of the MAT-LyLu cell line by 15 and 9%, respectively. Importantly, at the concentrations used, none of these drugs had effects on the proliferation or viability of either cell line. The results, taken together, would suggest strongly that functional VGSC expression enhances cellular motility of PCa cells. The relevance of these findings to the metastatic process in PCa is discussed.

A comparison between loop diathermy conization and cold-knife conization for management of cervical dysplasia associated with unsatisfactory colposcopy.

Eighty-six women with cervical dysplasia and unsatisfactory colposcopy were managed with excisional conization--43 with outpatient loop diathermy conization under local anesthesia and 43 matched controls with cold-knife conization as inpatients under general anesthesia. Both groups were similar in terms of age, parity, and severity of dyskaryosis on initial cytology, treatment success rates, and completeness of excision. However, loop diathermy conization was significantly quicker (2.8 +/- 2.9 min vs 14 +/- 18.6 min) and associated with less intraoperative blood loss (3.3 +/- 2.8 ml vs 79.1 +/- 74.6 ml) (P < 0.01) than cold-knife conization. Furthermore, the proportion of women with at least one complication was significantly less following loop (4.7%) than cold-knife conization (20.9%) (P < 0.05). We conclude that outpatient loop diathermy conization performed under local anesthesia is quicker and causes less intraoperative blood loss and immediate postoperative complications than cold-knife conization for management of cervical dysplasia associated with unsatisfactory colposcopy.

Outpatient excisional management of cervical intraepithelial neoplasia. A prospective, randomized comparison between loop diathermy excision and laser excisional conization.

OBJECTIVE: The purpose of our study was to compare loop diathermy excision and laser excisional conization with respect to treatment time, reliability, effectiveness, and safety. STUDY DESIGN: Three hundred women with cervical intraepithelial neoplasia attending our colposcopy clinic were randomized to treatment with either loop diathermy excision (group 1, n = 150) or carbon dioxide laser excisional conization (group 2, n = 150), both performed with local anesthesia on an outpatient basis. Student's t or Mann-Whitney test were used to compare continuous data; the chi 2 test was used for categoric data. RESULTS: The mean age, parity, histologic features, depth of excision, and occurrence of residual or recurrent disease were similar; however, the mean time required to complete treatment and hemostasis (2.5 +/- 3.6 vs 24.2 +/- 11.8 min), patient discomfort, blood loss (2.77 +/- 3.76 vs 27.15 +/- 17.51 ml; p < 0.001), and considerable thermal artifact affecting histologic interpretation of excision margins (5 cases vs 25 cases; p < 0.01) were significantly less in group 1 than in group 2. CONCLUSION: In our experience outpatient loop diathermy excision is an equally effective, quicker, safer, and more reliable excisional technique than laser excisional conization.