British Journal of Urology (1998), 82, 122–126 Bladder cancer recurrence by implantation of exfoliated cells: is c-linolenic acid an eVective tumoricidal agent? L.Z. SOLOMON, A.M. JENNINGS, S.J. FOLEY*, B.R. BIRCH and A.J. COOPER Department of Urology, Southampton University Hospitals NHS Trust, Southampton and *Department of Urology, St Mary’s Hospital, Portsmouth, UK Objective To compare the tumoricidal eBcacy of meglu- reduction with any other agent. Both epirubicin and mitomycin were as eCective as MeGLA in preventing mine c-linolenic acid (MeGLA), mitomycin C, epirub- icin and water on two urothelial cell lines, and to colony formation from suspended drug-sensitive (par- ental) cells. However, using multidrug-resistant (MDR) establish the eCect of serum protein levels derived from bladder cancer resection craters on the action of cell lines, only MeGLA prevented any colony forma- tion, although counts were greatly reduced by mito- these agents. Materials and methods The human urothelial cell lines mycin and epirubicin. Water was least eCective as a tumoricidal agent on both adherent and suspended MGHU-1 and RT112 and their drug-resistant variants were exposed to short pulses of aqueous MeGLA, cells. On the latter, water was markedly inactivated by adding 5% serum. TURBT waste irrigation fluid mitomycin, epirubicin and water. Both adherent and suspended cells were exposed to these agents. The was found frequently to contain such quantities of serous fluid contamination, as shown by albumin MTT viable biomass assay and a clonogenic assay were used to establish tumoricidal eBcacy. These estimates in waste fluid from 10 consecutive patients undergoing this procedure. experiments were then repeated to assess the eCect of added serum proteins on the test results. Estimates of Conclusion MeGLA is an eCective tumoricidal agent against both parental and MDR cell lines. Its eBcacy protein in the waste irrigation fluid from 10 patients undergoing transurethral resection of bladder tumour is maintained in the presence of clinically relevant serum contamination. (TURBT) were used to select the quantity of protein used in the study, to establish the clinical relevance. Keywords Water, exfoliated cells, gamma linolenic acid, bladder cancer, tumoricide, intravesical chemotherapy Results MeGLA caused >95% reduction in the residual viable biomass of adherent cells, compared with <50% TUR is worthwhile in reducing the risk of tumour Introduction recurrence [8–10]. Epirubicin and mitomycin have both been used for this purpose, while others advocate the Transurethral resection (TUR) with fulguration of the tumour remains the commonest approach to superficial use of water as a possible tumoricidal agent [11]. Several studies have shown a reduced risk of recur- bladder cancer. However, even with this treatment, up to 85% of patients will have recurrent tumours, often rence when the treatment protocol includes intravesical chemotherapy after TURBT [12–16]. Although this is a during the first year [1–3]. Most recurrences are prob- ably new tumours arising from other areas of dysplastic welcome improvement, recurrences may still occur pre- sumably because there is a high incidence of multidrug urothelium, but a significant proportion may result from tumour cell implantation [4], which may occur during resistance, which exists even before instituting chemo- therapy [17]. The osmotic eCects of water, and the eCects the endoscopic treatment of the original tumour [5]. This may arise by ‘seeding’ of detached tumour cells of many other commonly used tumoricidal drugs, are diminished in the presence of blood, which may reduce after trauma to the mucosa, which acts by facilitating the reception of ‘seeds’ [6,7], or lowering the resistance its eCectiveness as a lytic agent [18]. The need for a novel compound that is not compromised by resistance of the tissues to the original carcinogenic factor [4]. It is therefore recommended that at the very least, a single phenomena or inactivation in the presence of body fluids is clear. instillation of a cytotoxic drug within 24 h of the initial Meglumine c-linolenic acid (Me-GLA) may be an eCec- tive tumoricidal agent. It is well tolerated intravesically Accepted for publication 17 March 1998 122 © 1998 British Journal of Urology