RESUMEN
Ovarian cancer (OC), is a disease difficult to diagnose in an early stage implicating a poor prognosis. The 5-year overall survival in Belgium has not changed in the last 18 years and remains 44 %. There is no effective screening method (secondary prevention) to detect ovarian cancer at an early stage. Primary prevention of ovarian cancer came in the picture through the paradigm shift that the fallopian tube is often the origin of ovarian cancer and not the ovary itself. Opportunistic bilateral salpingectomy (OBS) during benign gynaecological and obstetric surgery might have the potential to reduce the risk of ovarian cancer by as much as 65 %. Bilateral risk-reducing salpingectomy during a benign procedure is feasible, safe, appears to have no impact on the ovarian function and seems to be cost effective. The key question is whether we should wait for a RCT or implement OBS directly in our daily practice. Guidelines regarding OBS within our societies are therefore urgently needed. Our recommendation is to inform all women without a child wish, undergoing a benign gynaecological or obstetrical surgical procedure about the pro's and the con's of OBS and advise a bilateral salpingectomy. Furthermore, there is an urgent need for a prospective registry of OBS. The present article is the consensus text of the Flemish Society of Obstetrics and Gynaecology (VVOG) regarding OBS.
RESUMEN
Until now hormonal regulation of flavin-containing monooxygenase (FMO) has been studied to a limited extent and all experiments reported so far have been carried out in vivo using invasive techniques. In order to examine whether in vitro models could be applied to study the regulation of FMO, pure cultures of rat hepatocytes and their co-cultures with primitive bile-duct epithelial cells have been used. Since the addition of foetal calf serum (FCS) to the medium, usually done to improve cell attachment, could interact with some hormones, the effect of its removal on FMO activity has been investigated. Furthermore, to find out if in vitro results comparable with the in vivo situation could be obtained, phenobarbital was added and its effect on the FMO system was measured. In pure hepatocyte cultures FMO activity declined continuously as a function of culture time, and after 6 days it was only 15% of that obtained for freshly isolated hepatocytes. In contrast, in co-cultures after an initial decrease a steady-state situation was maintained at a level of approximately 37% of the initial value. This observation was noted from day 7 onwards and for at least 1 wk. It was also observed that in both culture systems, the various media had no statistically significant effect on FMO activity expressed in nmol methimazole/min/mg microsomal protein. In pure hepatocyte cultures, however, addition of FCS and phenobarbital significantly increased the microsomal protein content per culture dish in comparison with the value obtained for serum-free medium. In the latter case deterioration and loss of hepatocytes in the absence of FCS occurred. In conclusion, the expression of FMO is better and longer maintained in co-cultures than in pure cultures. The removal of FCS from the medium in co-cultures does not affect FMO activity. Since addition of phenobarbital has no inducing effects on FMO activity, as is also the case in vivo, the results support the idea of using co-cultures of rat hepatocytes as an in vitro model for regulation studies of FMO.
RESUMEN
The determination of the mixed function flavin-containing monooxygenase activity in rat liver and in hepatocytes and their cultures by spectrophotometric measurement of the oxygenation of methimazole is complicated by an inhibition caused by some of the reagents used during this method. Optimal conditions were determined for measuring this enzyme activity in microsomal preparations of rat liver and its hepatocytes. Optimal flavin-containing monooxygenase activities were obtained for measurements performed in a 0.25 M N-[2-hydroxy-1,1-bis(hydroxymethyl)ethyl]glycine-EDTA buffer at pH 8.7 and at a methimazole concentration of 2 mM. Data are also presented which show that no interferences caused by either cytochrome P450-dependent enzymes or by the reduction of methimazole disulfide by glutathione have to be taken into account when determining methimazole oxygenation. Finally, the above assay was also used to study flavin-containing monooxygenase activity in primary monolayer cultures of hepatocytes for 6 days.
