[Sacral neuromodulation with InterStim™ system: Results from the French national register]. / Neuromodulation sacrée avec le système InterStim™ : résultats du registre national français.

AIM: To analyse current practice patterns and to evaluate (long-term) effectiveness and adverse events of sacral neuromodulation with InterStim™ Therapy based on data collected in a national register and to discuss the strengths and weaknesses of the register. PATIENTS AND METHODS: This is a French multicenter prospective observational trial including patients with a permanent implant (2003-2009). Voiding diary variables and patient satisfaction were analysed based on last follow-up visit since implantation. RESULTS: One thousand four hundred and eighteen patients (median age: 63 years, 1206 females) were included in the database (median follow-up: 12 months). One thousand and eighty-nine patients had non-neurological disease. The principal diagnosis was overactive bladder syndrome ([OAB], n=1170) and retention (n=151). Implantation occurred in 1358 patients; 1172 patients had greater than or equal to one registered follow-up. Clinical improvement of greater than or equal to 50% was seen in 447/527 patients with OAB at 12 months follow-up (median number of voids per 24 hours decreased from 15 at baseline to 8 at 12 months) and in 42/54 of patients with retention (median number of catheterization per 24 hours dropped from 5 at baseline to 0 at 12 months). Clinical improvement remained relatively stable up to 60 months. Median patient satisfaction with treatment was between 60 and 80%. Five hundred and twenty-four patients had at least one adverse event; loss of efficacy (n=244) occurred most frequently. CONCLUSIONS: In this large database sacral neuromodulation with InterStim™ Therapy seems to be an effective treatment through routine practice in the long-term (up to 60 months) for patients refractory to medical treatment.

Orai1 contributes to the establishment of an apoptosis-resistant phenotype in prostate cancer cells.

The molecular nature of calcium (Ca(2+))-dependent mechanisms and the ion channels having a major role in the apoptosis of cancer cells remain a subject of debate. Here, we show that the recently identified Orai1 protein represents the major molecular component of endogenous store-operated Ca(2+) entry (SOCE) in human prostate cancer (PCa) cells, and constitutes the principal source of Ca(2+) influx used by the cell to trigger apoptosis. The downregulation of Orai1, and consequently SOCE, protects the cells from diverse apoptosis-inducing pathways, such as those induced by thapsigargin (Tg), tumor necrosis factor α, and cisplatin/oxaliplatin. The transfection of functional Orai1 mutants, such as R91W, a selectivity mutant, and L273S, a coiled-coil mutant, into the cells significantly decreased both SOCE and the rate of Tg-induced apoptosis. This suggests that the functional coupling of STIM1 to Orai1, as well as Orai1 Ca(2+)-selectivity as a channel, is required for its pro-apoptotic effects. We have also shown that the apoptosis resistance of androgen-independent PCa cells is associated with the downregulation of Orai1 expression as well as SOCE. Orai1 rescue, following Orai1 transfection of steroid-deprived cells, re-established the store-operated channel current and restored the normal rate of apoptosis. Thus, Orai1 has a pivotal role in the triggering of apoptosis, irrespective of apoptosis-inducing stimuli, and in the establishment of an apoptosis-resistant phenotype in PCa cells.

Intermediate-conductance Ca2+-activated K+ channels (IKCa1) regulate human prostate cancer cell proliferation through a close control of calcium entry.

Accumulating data point to K(+) channels as relevant players in controlling cell cycle progression and proliferation of human cancer cells, including prostate cancer (PCa) cells. However, the mechanism(s) by which K(+) channels control PCa cell proliferation remain illusive. In this study, using the techniques of molecular biology, biochemistry, electrophysiology and calcium imaging, we studied the expression and functionality of intermediate-conductance calcium-activated potassium channels (IK(Ca1)) in human PCa as well as their involvement in cell proliferation. We showed that IK(Ca1) mRNA and protein were preferentially expressed in human PCa tissues, and inhibition of the IK(Ca1) potassium channel suppressed PCa cell proliferation. The activation of IK(Ca1) hyperpolarizes membrane potential and, by promoting the driving force for calcium, induces calcium entry through TRPV6, a cation channel of the TRP (Transient Receptor Potential) family. Thus, the overexpression of the IK(Ca1) channel is likely to promote carcinogenesis in human prostate tissue.

Systematization of the vesical and uterovaginal efferences of the female inferior hypogastric plexus (pelvic): applications to pelvic surgery on women patients.

OBJECTIVE: To locate and describe the various efferences of the plexus in order to make it easier to avoid nerve lesions during pelvic surgery on women patients through a better anatomical knowledge of the inferior hypogastric plexus (IHP). MATERIALS AND METHODS: We dissected 27 formalin embalmed female anatomical subjects, none of which bore any stigmata of subumbilical surgery. The dissection was always performed using the same technique: identification of the inferior hypogastric plexus, whose posterior superior angle follows on from the hypogastric nerve and whose top, which is anterior and inferior, is located exactly at the ureter's point of entry into the base of the parametrium, underneath the posterior layer of the broad ligament. RESULTS: The IHP is located at the level of the posterior floor of the pelvis, opposite to the sacral concavity. Its top, which is anterior inferior, is at the point of contact with the ureter at its entry into the posterior layer of the broad ligament. The uterovaginal, vesical and rectal efferences originate in the paracervix. Three efferent nerves branch, two of them from its top and the third from its inferior edge: (1) A vaginal nerve, medial to the ureter, follows the uterine artery and divides into two groups: anterior thin, heading for the vagina and the uterus; posterior, voluminous, heading in a superior rectal direction (=superior rectal nerve). (2) A vesical nerve, lateral to the ureter, divides into two groups, lateral and medial. (3) The inferior rectal nerve emerges from the inferior edge of the IHP, between the fourth sacral root and the ureter's point of entry into the base of the parametrium. CONCLUSION: The ureter is the crucial point of reference for the IHP and its efferences and acts as a real guide for identifying the anterior inferior angle or top of the IHP, the origin of the vaginal nerve, the level of the ureterovesical junction and the division of the vesical nerve into its two medial and lateral branches. Dissecting underneath and inside the ureter and the uterine artery involves a risk of lesion of the vaginal nerve and its uterovaginal branches. Further forward, between the intersection and the ureterovesical junction, dissecting and/or coagulating under the ureter involves a risk of lesions to the vesical nerve, which are likely to explain the phenomena of denervation of the anterior floor encountered after certain hysterectomies and/or surgical treatments of vesicoureteral reflux.

The female inferior hypogastric (= pelvic) plexus: anatomical and radiological description of the plexus and its afferences--applications to pelvic surgery.

AIM OF THE STUDY: We wanted to determine the anatomical features of the inferior hypogastric plexus (IHP), and the useful landmarks for a safe surgical approach during pelvic surgery. MATERIALS AND METHODS: We dissected the IHP in 22 formolized female anatomical subjects, none of which bore any stigmata of subumbilical surgery. RESULTS: The inferior hypogastric plexus (IHP) is a triangle with a posterior base and an anterior inferior top. It can be described as having three edges and three angles; its inferior edge stretches constantly from the fourth sacral root to the ureter's point of entry into the posterior layer of the broad ligament; its cranial edge is strictly parallel to the posterior edge of the hypogastric artery, along which it runs at a distance of 10 mm; its posterior (dorsal) edge is at the point of contact with the sacral roots, from which it receives its afferences. They most frequently originate from S3 or S4 (60%) and then, in one or two branches, often from S2 (40%), never from S1 and in exceptional cases from S5 (20%). There are sympathetic afferences in 30% of cases, usually through a single branch of the second, third or fourth sacral ganglion. All IHPs have at least one sacral afference and sometimes there may be up to three afferences from the same sacral root. Its dorsal cranial angle, which is superior, comes after the SHP (hypogastric nerve or presacral nerve filament); its anterior inferior angle is located exactly at the ureter's point of entry into the posterior layer of the broad ligament. This is the top of the IHP; its posterior inferior angle is located at the point of contact with the fourth sacral root. At its entrance at the base of the parametrium the pelvic ureter is the anterior, fundamental positional reference for the IHP. The vaginal efferences come out of the top of the IHP through branches leading to the bladder, the vagina and the rectum, which originate through two trunks exactly underneath the crossing point of the ureter and the uterine artery: (i) one trunk leading to the bladder runs along and underneath the ureter and divides into two groups, which are lateral and medial, trigonal. (ii) the trunk leading to the vagina runs along the inferior edge of the uterine artery. At the point of contact with the lateral edge of the vagina, it splits into two groups: anterior thin and posterior voluminous. Some of its branches perforate the posterior wall of the vagina and are distributed to the rectovaginal septum in a tooth comb pattern. The inferior branches, which emerge from the inferior edge of the IHP, reach the rectum directly. The dissection of the 22 specimens allowed us to describe three efferent plexuses: a vaginal rectal plexus, a vesical plexus and a inferior rectal plexus. So the IHP's anterior, fundamental positional reference is the pelvic ureter at the point where it enters at the base of the parametrium, then at the crossing point of the uterine artery. The ureter is the vector for vesical efferences, the uterine artery is the vector for vaginal efferences, which are thus sent into the vesicovaginal septum and the rectovaginal septum. This surgical point of reference is of vital importance in nerve sparing during the course of a simple or extended hysterectomy. Any dissection carried out underneath and outside of the ureter inevitably carries a risk of lesions to its efferent, lateral vesical or medial, rectovaginal fibres.

Evidence for specific TRPM8 expression in human prostate secretory epithelial cells: functional androgen receptor requirement.

TRPM8 (melastatine-related transient receptor potential member 8), a member of the transient receptor potential (TRP) superfamily of cation channels, has been shown to be a calcium-channel protein. TRPM8 mRNA has also been shown to be overexpressed in prostate cancer and is considered to play an important role in prostate physiology. This study was designed to determine the androgen-regulation mechanisms for TRPM8 mRNA expression and to identify the phenotype of TRPM8-expressing cells in the human prostate. Our findings show that trpm8 gene expression requires a functional androgen receptor. Furthermore, this article argues strongly in favour of the fact that the trpm8 gene is a primary androgen-responsive gene. Single-cell reverse transcriptase PCR and immunohistochemical experiments also showed that the trpm8 gene was mainly expressed in the apical secretory epithelial cells of the human prostate and trpm8 down-regulation occurred during the loss of the apical differentiated phenotype of the primary cultured human prostate epithelial cells. The androgen-regulated trpm8 expression mechanisms are important in understanding the progression of prostate cancer to androgen-independence. These findings may contribute to design a strategy to predict prostate cancer status from the TRPM8 mRNA level. Furthermore, as the TRPM8 channel is localized in human prostate cells, it will be interesting to understand its physiological function in the normal prostate and its potential role in prostate cancer development.

An optimal bronchial tree may be dangerous.

The geometry and dimensions of branched structures such as blood vessels or airways are important factors in determining the efficiency of physiological processes. It has been shown that fractal trees can be space filling and can ensure minimal dissipation. The bronchial tree of most mammalian lungs is a good example of an efficient distribution system with an approximate fractal structure. Here we present a study of the compatibility between physical optimization and physiological robustness in the design of the human bronchial tree. We show that this physical optimization is critical in the sense that small variations in the geometry can induce very large variations in the net air flux. Maximum physical efficiency therefore cannot be a sufficient criterion for the physiological design of bronchial trees. Rather, the design of bronchial trees must be provided with a safety factor and the capacity for regulating airway calibre. Paradoxically, our results suggest that bronchial malfunction related to asthma is a necessary consequence of the optimized efficiency of the tree structure.

Ca2+ homeostasis and apoptotic resistance of neuroendocrine-differentiated prostate cancer cells.

Neuroendocrine (NE) differentiation is a hallmark of advanced, androgen-independent prostate cancer, for which there is no successful therapy. NE tumor cells are nonproliferating and escape apoptotic cell death; therefore, an understanding of the apoptotic status of the NE phenotype is imperative for the development of new therapies for prostate cancer. Here, we report for the first time on alterations in intracellular Ca(2+) homeostasis, which is a key factor in apoptosis, caused by NE differentiation of androgen-dependent prostate cancer epithelial cells. NE-differentiating regimens, either cAMP elevation or androgen deprivation, resulted in a reduced endoplasmic reticulum Ca(2+)-store content due to both SERCA 2b Ca(2+) ATPase and luminal Ca(2+) binding/storage chaperone calreticulin underexpression, and to a downregulated store-operated Ca(2+) current. NE-differentiated cells showed enhanced resistance to thapsigargin- and TNF-alpha-induced apoptosis, unrelated to antiapoptotic Bcl-2 protein overexpression. Our results suggest that targeting the key players determining Ca(2+) homeostasis in an attempt to enhance the proapoptotic potential of malignant cells may prove to be a useful strategy in the treatment of advanced prostate cancer.

Interplay between geometry and flow distribution in an airway tree.

Uniform flow distribution in a symmetric volume can be realized through a symmetric branched tree. It is shown here, however, by 3D numerical simulation of the Navier-Stokes equations, that the flow partitioning can be highly sensitive to deviations from exact symmetry if inertial effects are present. The flow asymmetry is quantified and found to depend on the Reynolds number. Moreover, for a given Reynolds number, we show that the flow distribution depends on the aspect ratio of the branching elements as well as their angular arrangement. Our results indicate that physiological variability should be severely restricted in order to ensure adequate fluid distribution through a tree.

The inferior hypogastric plexus (pelvic plexus): its importance in neural preservation techniques.

The progress in the surgery of male neurological cancers relies on the anatomico-surgical approach to the pelvic neural structures. The objective of our study was to provide a better understanding of the inferior hypogastric plexus (IHP) and its anatomical relationships in order to spare it during radical prostatectomy. Fifteen male formalin-preserved cadavers which had no sub-umbilical scar were used. In five subjects, the superior hypogastric plexus (SHP) and the pre-sacral plexus were displayed then the IHP and its sacral afferents (pelvic splanchnic nerves or erector nerves of Eckhardt) were dissected out. Serial sections of the IHP were then studied in ten subjects. This allowed its identification on certain imaging sections obtained in pelvic tumor pathology and these made up the "reference cuts". The IHP lies within a fibro-fatty plate which is flat, rectangular, sub-peritoneal, sagittal and symmetrical. It arises at the level of the intersection between the vas deferens and the terminal pelvic ureter and follows the postero-lateral aspect and circumvolutions of the seminal vesicle, with which there is a plane of surgical cleavage. The seminal vesicle is, therefore, an essential landmark for this neural structure. The plane of this cleavage may be used in pelvic cancer surgery. The safest technical means of respecting sexual function and the integrity of the IHP is to keep it at a distance. The preservation of a lateral layer of the seminal vesicle is probably a method of limiting these complications as long as this does not conflict with the oncological clearance. An irregular communicating branch was found in one of five cases between the IHP, the sacral plexus and the pudendal nerve. This communicating branch lay immediately behind the intersection between the vas deferens and the ureter in the sacral concavity. It overhangs the IHP in the seminal vesicle. Impotence remains a frequent complication after radical prostatectomy. The methods of neural preservation at the prostatic apex are known but neural preservation should also be carried out posteriorly at the lateral pole of the seminal vesicle. The possibility of posterior neural preservation may be assessed pre-operatively by study of the "reference sections". The cleavage plane between the seminal vesicle and the IHP may be used intra-operatively to spare the IHP. The cavernous nerve in particular emerges at the antero-inferior border of the IHP before running along the postero-lateral aspect of the prostate. It therefore passes in contact with the seminal vesicle and may as a result be injured during radical prostatectomy with vesiculectomy. A proximal communicating branch between the IHP and the pudendal nerve is irregular. Such communicating branches may explain a better recovery of sexual function in curative neurological cancer surgery. The essential relationship of the IHP is with the seminal vesicle. The two are in tight contact and the seminal vesicle has a true plane of surgical cleavage with IHP. The risk of injuries to the posterior erectile mechanisms can be reduced either by using the cleavage plane between the IHP and seminal vesicle or by leaving a layer of the seminal vesicle when the oncological conditions allow. During celio-surgery, the operator must be careful to retract the little bands of the seminal vesicle and divide the fibrous and vascular tracts which tighten during this maneuver. During an abdominal approach, dissection of the seminal vesicle takes place at the bottom of a real pit. The operator must carry out the division leaving a layer of the seminal vesicle in place rather than trying to extract all the seminal vesicle by placing the forceps blindly. This maneuver is naturally dependent on the oncological situation. The anatomical confirmation of a regular or irregular proximal or distal communicating branch between the IHP and the pudendal nerve is probably an explanation for the sometimes uncertain results of new techniques of neural preservation in curative cancer surgery.

[Comparison of 3 self lubrificated urethral catheters: prospective study on 27 patients]. / Comparaison de trois sondes urétrales droites autolubrifiées: étude prospective chez 27 patients.

Clean intermittent catheterization has become a usual procedure in urologic practice. Self lubrificated catheters are nowadays accepted as the most efficient. This randomised and prospective study compared tolerance and efficiency in a group of 27 patients of three well known catheters (12 charriere, straight): Flocath (Ruschcare), Lofric (Astratech) and Easycath (Coloplast). The systematic comparison of this three catheters did not allow to put in a prominent position one of these. The three catheters are extremely close in terms of tolerance and performance.

[Recurrent peri-stomal varix hemorrhage after diversion using the Bricker's technique]. / Hémorragies récurrentes par des varices péri-stomiales après dérivation selon Bricker.

Peristomal varices can occur in patients with gastrointestinal or urinary diversions associated with portal hypertension. It is now no longer rare to propose radical surgery for invasive bladder tumours in patients also suffering from hepatic cirrhosis, responsible for specific subsequent complications. Less than ten cases of varicose haemorrhages have been described on ileal bladders. The authors report the case of a patient with cirrhosis (Child B) treated surgically (radical cystoprostatectomy and Bricker transileal cutaneous diversion) for invasive bladder tumour. Episodes of bleeding varices occurred two months after surgery. Repeated and abundant haemorrhage led to the placement of an intrahepatic shunt (TIPS) allowing reduction of the portal hypertension and the severity of the bleeding. When local control of the bleeding is no longer possible, reduction of the portosystemic pressure gradient is required. TIPS is an effective alternative to surgical shunts, responsible for high morbidity and mortality in these debilitated patients.

[Long-term results of interferential current stimulation in the treatment of bladder instability]. / Résultats à long-terme de la stimulation par courants interférentiels dans le traitement de l'instabilité vésicale.

OBJECTIVE: To study the late results of interferential current stimulation in the treatment of detrusor instability. MATERIAL AND METHODS: 62 patients with detrusor instability refractory to medical treatment by anticholinergic drugs were treated by interferential current stimulation. This technique combines the advantages of retraining stimulation with external application. This retrospective study was based on 62 patients (43 children, 11 men and 8 women) presenting with detrusor instability between January 1990 and December 1997. All patients were assessed clinically and by a radiological, bacteriological and urodynamic work-up prior to treatment. The mean follow-up was 5 years (range: 18 months to 10 years). RESULTS: The results of this technique were excellent, with 80.9% of cures at one year, but they tended to fade over time to 40% of cures at 5 years. However, results which deteriorate after one year can generally be maintained by performing 5 maintenance sessions every 12 or 18 months. CONCLUSION: Treatment of detrusor instability by interferential current is a reliable technique which constitutes an alternative to the other methods of retraining stimulation and can be performed in cases of instability refractory to anticholinergic drugs, before considering neuromodulation or surgery. Five to 10 maintenance sessions every 12 or 18 months ensure stable long-term results in the majority of cases.

Volume-regulated chloride conductance in the LNCaP human prostate cancer cell line.

Patch-clamp recordings were used to study ion currents induced by cell swelling caused by hypotonicity in human prostate cancer epithelial cells, LNCaP. The reversal potential of the swelling-evoked current suggested that Cl(-) was the primary charge carrier (termed I(Cl,swell)). The selectivity sequence of the underlying volume-regulated anion channels (VRACs) for different anions was Br(-) approximately I(-) > Cl(-) > F(-) > methanesulfonate >> glutamate, with relative permeability numbers of 1.26, 1.20, 1.0, 0.77, 0.49, and 0.036, respectively. The current-voltage patterns of the whole cell currents as well as single-channel currents showed moderate outward rectification. Unitary VRAC conductance was determined at 9.6 +/- 1.8 pS. Conventional Cl(-) channel blockers 5-nitro-2-(3-phenylpropylamino)benzoic acid (100 microM) and DIDS (100 microM) inhibited whole cell I(Cl,swell) in a voltage-dependent manner, with the block decreasing from 39.6 +/- 9.7% and 71.0 +/- 11. 0% at +50 mV to 26.2 +/- 7.2% and 14.5 +/- 6.6% at -100 mV, respectively. Verapamil (50 microM), a standard Ca(2+) antagonist and P-glycoprotein function inhibitor, depressed the current by a maximum of 15%. Protein tyrosine kinase inhibitors downregulated I(Cl,swell) (genistein with an IC(50) of 2.6 microM and lavendustin A by 60 +/- 14% at 1 microM). The protein tyrosine phosphatase inhibitor sodium orthovanadate (500 microM) stimulated I(Cl,swell) by 54 +/- 11%. We conclude that VRACs in human prostate cancer epithelial cells are modulated via protein tyrosine phosphorylation.

Tendinous arch of the pelvic fascia: application to the technique of paravaginal colposuspension.

The authors give a description of the anatomy and topography of the tendinous arch of the pelvic fascia (TAPF), in order to facilitate its location during surgery. 35 TAPF in 25 female cadavers were dissected. The reproducibility of the landmarks was then verified at laparotomy. The TAPF can be easily identified and its resistance remains constant, even when the pelvic floor is hypotrophic. Its anterior extremity (d2) is at about 46 mm on a line perpendicular to the anterior edge of the pectineal ligament (35-55 mm), next to the pubovesical ligament. Its median part (dl) is perpendicular to the obturator foramen at a site located at an average of 30 mm below the obturator foramen (25-50 mm). Its posterior end is located at the ischial spine. These anterior landmarks, the only ones useful during surgery, allow its very easy location with the palmar surface of the finger. Testard and Delancey demonstrated the major role of the TAPF in stabilising the urethra submitted to strain. Richardson described a technique of paravaginal suspension for curing paravaginal fascial defect. The TAPF has never been well described, but his work allows its easy location during surgery. The suture of the vagina to the TAPF allows a more physiologic and stronger suspension of the bladder neck than other classical techniques.

Microwave thermochemotherapy in the treatment of the bladder carcinoma--electromagnetic and dielectric studies--clinical protocol.

Microwave thermotherapy is currently used in clinical routines for benign prostatic hyperplasia treatments. The temperature increase is obtained using an endocavitary microwave applicator placed in the prostatic urethra. This urethral applicator after a technical modification can be placed inside the bladder in order to potentiate the effects of the treatment by chemotherapy of vesical carcinoma. This paper deals with electromagnetic studies of this new endocavitary applicator. First of all, the experimental determination of the dielectric permittivities for the propagation domain characterization is achieved in order to be used in the electromagnetic model. Compared to experimental results, these simulations obtained by the finite-difference time-domain formalism allow us to determine the electromagnetic performance of this applicator. Finally, the in vivo study realized on anesthetized dogs to determine the therapeutic protocol associating chemotherapy and thermotherapy in the treatment of the bladder cancer is presented.

Variations of the radial artery in man.

Variations of the radial artery are common in man. A high origin, due either to precocious bifurcation or to persistent duplication of the brachial artery, and the presence of a superficial dorsal ramus in the forearm suggest hemodynamic insufficiency of the axial vascular network allowing persistence of certain portions of the superficial system of the upper limb. Confusion of these unusual arteries with the subcutaneous veins may explain the accidental injection of drugs and distal necrosis of the limb. Knowledge of these variations may facilitate ascending catheterization of the cardiac cavities.

Anatomic variation in the origin of the main renal arteries: spiral CTA evaluation.

The aim of this study was to provide quantitative data on the origin and trajectory of the main renal arteries using spiral CT angiography and arteriography. Normal renal artery anatomy was assessed on spiral CT angiography (axial transverse sections and shaded-surface-display reconstructions) in 100 patients referred for renal arteriography who had no significant renal artery stenosis. Two hundred major renal arteries were studied. The vast majority of right (88 %) and left (87 %) renal arteries originated between the lower third of the first lumbar vertebra and the lower border of the second lumbar vertebra. In 50 patients both ostia were at the same level; in the remaining 50 patients, the right ostium was located above the left in 37 patients. On the right, the angle of origin varied from -10 to + 55 degrees (mean + 24 degrees ). On the left, the angle of origin varied from + 30 to -55 degrees (mean -11 degrees ). Spiral CT angiography provides additional anatomic data, notably regarding the angle of origin of the renal arteries, that is potentially useful for planning interventional procedures.

[Study of the synergy of microwave hyperthermia/intravesical chemotherapy in the prevention of recurrences of superficial tumors of the bladder]. / Etude de la synergie hyperthermie micro-onde/chimiothérapie intravésicale dans la prévention des récidives des tumeurs superficielles de vessie.

OBJECTIVES: Preliminary clinical studies of the combination of hyperthermia and intravesical chemotherapy indicated very encouraging results in favour of multidisciplinary treatment of recurrent superficial bladder tumours. The authors studied the in vitro and early in vivo effects of this treatment. MATERIAL AND METHODS: An intravesical catheter equipped with a microwave antenna was used for hyperthermia in vivo in dogs. The temperature was controlled by two intravesical thermocouples and 4 transducers on the bladder wall. 0, 40 or 80 mg of mitomycin were instilled in 60 ml of physiological saline. Dogs were sacrificed after each one-hour session, and histological intravesical lesions were defined as grade 0, 1 or 2 corresponding to absence of lesions, or the presence of inflammatory lesions or urothelial lesions, respectively. In vitro, the first step consisted of creation of an immortalized tumour cell line from a grade II bladder papilloma. This HVT 196 cell line was incubated between 37 degrees C and 44 degrees C with increasing mitomycin concentrations of 0 to 10 micrograms per ml. The cytotoxicity was measured by the MTT quantitative colorimetric method. RESULTS: In vivo, in 8 dogs, histological analysis of the comparative cytotoxicity of the various treatments confirmed the synergistic effect of heat and mitomycin C. In dogs treated at 45 degrees C, marked urothelial lesions were observed, regardless of the mitomycin C concentration. The in vitro comparative toxicity study on our cell line showed a much more intense cytotoxic effect with combined treatment than with cytostatic treatment alone. Expressed as the percentage of cytotoxicity compared to a control cell pool for a concentration of 1 microgram per ml. the temperature rise of the medium between 37 degrees C and 44 degrees C was accompanied by a cytotoxic effect of 8.4% and 98.41% respectively. CONCLUSION: A possible clinical application is potentiation of the action of mitomycin C by hyperthermia in the prevention of recurrent superficial bladder tumours, achieving increased efficacy and/or a decreased number of instillations.