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Bernard Malavaud

Publications and source records attributed to Bernard Malavaud.

At least 19 recordsLinked to original sources

Development of a seeded scaffold in the great omentum: feasibility of an in vivo bioreactor for bladder tissue engineering.

OBJECTIVES: Tissue engineering is very promising in bladder reconstruction. However, one of the main problems is to limit the development of ischaemic fibrosis during tissue maturation. We describe a model using the omentum as an in vivo bioreactor for a previously seeded scaffold. METHODS: Bladder biopsies were taken from five female pigs, from which both urothelial and smooth muscle cells cultures were made. These cultured cells were used to seed a sphere-shaped small intestinal submucosa (SIS) matrix, which was transferred into the omentum after 3 wk of cell growth. The grafts were harvested 3 wk later and histologic, immunohistochemical, and functional studies were performed. RESULTS: We obtained a highly vascularized tissue-engineered construct that contracted in response to acetylcholine stimulation. The wall thickness was 4mm, on average. Histologic and immunostaining analysis of the construct confirmed the presence of a multilayer urothelium on the luminal aspect and deeper fascicles organised tissue composed of differentiated smooth muscle cells and mature fibroblasts without evidence of inflammation or necrosis. Large- and small-diameter vessels were clearly identified histologically in the tissue obtained. CONCLUSION: The omentum permitted in vivo maturation of seeded scaffolds with the development of a dense vascularisation that is anticipated to prevent fibrosis and loss of contractility. This in vivo maturation into the omentum could be the first step before in situ implantation of the construct.

Animals↗

Seasonality of serum prostate-specific antigen levels: a population-based study.

OBJECTIVE: The measurement of PSA serum levels is central to all early detection programs for prostate cancer. Although individual PSA values were known to fluctuate in the short and long term, the influence of insolation and seasons on PSA had not been addressed to date. To assert the relationship between total and free PSA and meteorological data in 8644 participants (55-70 years) in the French arm of the ERSPC study. METHODS: Blood sample was taken at the local laboratory after informed consent and frozen sera were sent for central testing of total and free PSA. PSA measurement was performed within 7 days on the Access 1.0 automat with Hybritech reagents. Monthly meteorological data -- insolation, daily temperatures and rain precipitations -- were obtained from the local branches of the National Meteorology Agency. RESULTS: Total PSA -- but not free PSA -- was correlated with insolation, that is the monthly accrual in hours of sunshine during which the intensity was higher than 120 Watt x m(-2) (r = 0.05 (95%CI: 0.03-0.07; p < 0.0001)) while no relationships were shown between insolation and percent-free PSA (free PSA divided by the total PSA). Interdependence between total PSA and insolation was also apparent with respect to the 3 ng/mL ERSPC cutoff for recommending biopsies (213.1 vs. 206.2 hours, p = 0.004). Such relationship was even more evident in summer when the tested participants more often had a PSA > 3 ng/mL (17.1% vs. 14.3%, p = 0.0006) than in the rest of the year, resulting in 23% more chances of being referred for biopsies (Odds ratio 1.23, 95%CI: 1.10-1.40). CONCLUSIONS: Total PSA was shown to be strongly associated with insolation and seasons while the percent-free PSA was not influenced.

Aged↗

Uterus, fallopian tube, ovary and vagina-sparing laparoscopic cystectomy: technical description and results.

OBJECTIVES: The purpose of our study was to demonstrate, describe, and assess the results of the technique of laparoscopic cystectomy sparing the uterus, fallopian tubes, ovaries, and vagina. PATIENTS AND METHODS: Between July 2004 and December 2005, 13 women with neurogenic vesical dysfunction (mean age: 53.3+/-13.0 yr) underwent laparoscopic cystectomy sparing the uterus, fallopian tubes, ovaries, and vagina. A noncontinent transileal Bricker diversion was performed extracorporeally in each case. Parameters studied were the pre-, peri- and postoperative data. RESULTS: Mean duration of the operation was 325+/-36 min, and mean blood loss was 323.1+/-246.3 ml. No conversion was required. One perioperative complication was observed: a tear in a branch of the right hypogastric vein, which was sutured under laparoscopy. One patient was transfused during surgery (2 units of blood). No early or late postoperative complications were observed. One patient required transfusion of 2 units of red blood cell concentrate on the first day after surgery. None of the patients required opiate analgesia in the postoperative period. The analgesic regimen used was paracetamol and nefopam in all cases. The pain score on an analogic visual scale was less than 4 in all cases. Resumption of transit was not delayed in any of the patients. Mean hospital stay was 11.6+/-1.9 d. Over an average follow-up of 7.4+/-5.4 mo, none of the patients developed late complications. Before surgery, 77% of the women were sexually active; 80% of them were sexually active 4 mo after the surgery. CONCLUSIONS: Laparoscopic cystectomy sparing the uterus, fallopian tubes, ovaries, and vagina is feasible. This operation has low morbidity and requires only a limited stay in hospital.

Adult↗

Evaluation of sexual function in young men with spina bifida and myelomeningocele using the International Index of Erectile Function.

OBJECTIVES: To assess sexual function in young men with spina bifida and myelomeningocele. METHODS: Between November 2003 and February 2004, a cross-sectional study was performed in 55 men older than 18 years of age who had been regularly followed up for myelomeningocele since childhood, between 1961 and 1985, in the Pediatric Internal Surgery Department. The International Index of Erectile Function (IIEF) questionnaire was mailed to each man. RESULTS: The response rate was 72.7%. Of the 40 men who replied, 16 (40%) had had sexual intercourse at least once during the previous month. These were the older men (age 31.9 +/- 5.7 years versus 27.7 +/- 5.5 years, P = 0.027). The IIEF scores for the whole group were erectile function 11.61 +/- 9.44, orgasmic function 3.53 +/- 3.86, sexual desire 6.94 +/- 2.4, intercourse satisfaction 3.7 +/- 4.81, and overall satisfaction 4.7 +/- 3.34. According to the classification of Cappelleri, of the 16 men who had had sexual intercourse during the previous month, 4 had no erectile dysfunction, 3 had mild, 4 mild to moderate, and 5 severe dysfunction. Erectile function was statistically related to the ability to maintain erections (mean IIEF score 4 and 5 for men with no erectile dysfunction versus a mean IIEF score of 4 and 5 for men with erectile dysfunction: 4.75 +/- 0.5 versus 2.00 +/- 1.32, P = 0.011 for IIEF score of 4 and 4.50 +/- 1.5 versus 3 +/- 2, P = 0.040 for IIEF score of 5). CONCLUSIONS: Young adult men with spina bifida and myelomeningocele begin sexual activity late. Moreover, 75% have erectile dysfunction that is related to difficulty in maintaining erections.

Adult↗

The effect of ofloxacin on bacillus calmette-guerin induced toxicity in patients with superficial bladder cancer: results of a randomized, prospective, double-blind, placebo controlled, multicenter study.

PURPOSE: We determined whether prophylaxis with ofloxacin could decrease the toxicity of bacillus Calmette-Guerin for transitional cell carcinoma of the bladder. We also investigated the impact of ofloxacin on bacillus Calmette-Guerin antitumor efficacy. MATERIALS AND METHODS: In this randomized, double-blind, multicenter study 115 patients with primary or recurrent superficial bladder cancer (Ta/T1, CIS, G1-G3) and no prior bacillus Calmette-Guerin treatment were randomized to induction treatment with intravesical bacillus Calmette-Guerin (6 plus 3 instillations) plus 200 mg ofloxacin in group 1 or plus placebo in group 2. Adverse events were assessed using a detailed grid of classification for bacillus Calmette-Guerin related adverse events. Mean patient age +/- SD was 65.6 +/- 10.4 years in the 57 group 1 patients and 65.7 +/- 8.7 years in the 58 in group 2. Median followup was 369 and 374 days in groups 1 and 2, respectively. RESULTS: Ofloxacin significantly decreased by 18.5% the incidence of class II or higher moderate and severe adverse events between instillations 4 and 6. The percent of class III adverse events was significantly decreased by ofloxacin between instillations 1 and 9. Although ofloxacin decreased adverse events involving the lower urinary tract, it did not prevent class I adverse events. Compliance with full bacillus Calmette-Guerin treatment was also improved. Of patients in group 1, 80.7% received 9 instillations compared with 65.5% in group 2 (p = 0.092). At 12 months recurrence and progression rates in group 1 and 2 were 12.7% and 17.2%, and 5.5% and 1.7%, respectively. CONCLUSIONS: Prophylactic ofloxacin decreased the incidence of moderate to severe adverse events associated with bacillus Calmette-Guerin intravesical therapy, particularly class III events, which are primarily associated with patient dropout. Compliance with induction and maintenance therapy may be improved by adjuvant ofloxacin therapy. However, long-term comparative studies with other preventive strategies must be done to confirm these initial findings with compliance and recurrence-free survival as the primary end points.

Adjuvants, Immunologic↗

[Treatment of bladder outlet obstruction secondary to suburethral tape by section of the tape].

OBJECTIVES: To determine the results of treatment of chronic urinary retention secondary to bladder outlet obstruction complicating retropubic suburethral insertion of Tension-free Vaginal Tape (TVT) by section of this tape. MATERIAL AND METHODS: Between June 2000 and December 2004, 30 women with a mean age of 63.5 +/- 11.6 years underwent a single lateral urethral section of Tension-free Vaginal Tape to treat bladder outlet obstruction secondary to retropubic suburethral TVT insertion. Success was defined by resolution of the symptoms, a maximum urine flow rate greater than 15 ml/s and a post-voiding residual less than 50 ml and failure was defined by persistence of at least one of these three criteria. RESULTS: The mean interval between TVT placement and tape section was 12.7 +/- 14.7 months. The mean follow-up was 25.8 +/- 7.8 months. The cure rate was 70%. One complication (a bladder wound) was observed. Postoperatively, two patients (70%) developed recurrence of stress urinary incontinence. CONCLUSION: The treatment of chronic bladder outlet obstruction after retropubic TVT placement to treat stress urinary incontinence by single lateral urethral section of this tape is a simple and effective technique with low morbidity, accompanied by a very low urinary incontinence recurrence rate.

Female↗

[Linguistic validation of the "Brief Index of Sexual Functioning for Women"].

UNLABELLED: Application to the study of sexuality in a population of 93 French women. OBJECTIVES: This study was designed to linguistically validate the French version of the BISF-W (Brief Index of Sexual Functioning for Women) which provides a quantitative and qualitative assessment of female sexuality according to 7 dimensions. This version was then used to study the impact of recognized factors of sexual dysfunction on a control population. MATERIAL AND METHOD: The BISF-W a self-administered quality of life questionnaire developed by Rosen, was translated and linguistically validated. This questionnaire comprises 22 questions in 7 dimensions investigating all aspects of female sexuality: D1 (desire), D2 (arousal), D3 (frequency of sexual activity), D4 (receptiveness), 05 (pleasure, orgasm), D6 (relational satisfaction), D7 (problems affecting sexuality), Composite Score (CS) D1+D2+D3+D4+D5+D6+07. The French version was administered to a study population of 93 women: 49 derived from gynaecology or urology departments and 44 derived from the general population. We calculated and compared the scores of the various dimensions of the BISF-W according to factors able to modify sexuality, such as menopause, age or parity. RESULTS: The results of our study show an alteration of the various dimensions of sexuality in elderly patients (D2, D5, D6, CS; p<0.05) or postmenopausal patients (D2, D5, D6, CS, p<0.05) and in multiparous women. CONCLUSION: The French version of the BISF-W gives results in line with the literature and demonstrates changes of sexuality as a function of the above mentioned variables.

Adult↗

[Laparoscopic live donor nephrectomy: surgical technique and results].

OBJECTIVE: To report the results of laparoscopic live donor nephrectomy (LLDN) and to describe our technique. MATERIAL AND METHODS: We retrospectively reviewed 47 laparoscopic live donor nephrectomies performed between January 1999 and July 2005. Several parameters were studied: donor clinical characteristics, intraoperative and postoperative complications, operating time and warm ischaemia time. This series comprised 26 women (55.31%) and 21 men (44.68%) with a mean age of 48 +/- 20 years. Donor nephrectomy was mainly performed on the left kidney (85.37%). It was performed by lumbar endoscopy in the first 20 cases and by laparoscopy in 27 cases. Kidney extraction was performed via an incision between two trocar orifices for the first cases and via an iliac incision for the last 18 cases. RESULTS: The mean operating time was 189 min with a mean blood loss of 127 ml. Warm ischemia time was 6 minutes. Open conversion was required in two cases: renal vein injury in one case and an obese donor with difficulties of dissection in the other case. Surgical revision was required in only one case (haemoperitoneum secondary to genital vein injury). A trocar orifice abscess was observed in one case and prolonged ileus was reported in 2 cases. In the recipient, a urinary anastomotic fistula was observed secondary to ischaemic necrosis of the distal segment of the ureter. Late complications were essentially vascular (19.14%). A right renal graft was lost due to an error of compatibility. Mean serum creatinine was 132 +/- 6.5 micromol/l at 3 months for the other recipients. CONCLUSION: Our experience confirms the feasibility and efficacy of laparoscopic live donor nephrectomy. Intraoperative and postoperative complications and the conversion rate were low. Renal function was rapidly restored in the recipient. The morbidity of this technique is low, but there is a high risk of vascular complications at the beginning of the operator's experience.

Female↗

[Comparison of cavernometry and duplex ultrasound in the diagnosis of veno-occlusive erectile dysfunction].

OBJECTIVES: To compare pulsed duplex ultrasound and cavernometry in the aetiological diagnosis of veno-occlusive erectile dysfunction. MATERIAL AND METHODS: Between September 1995 and January 2005, 81 patients with a mean age of 48.45 +/- 12.35 years consulting for erectile dysfunction were investigated by cavernometry and pulsed duplex ultrasound before and after sensitization by intracavernous injection of 10 microg/ml of prostaglandin. The results of these two examinations were compared by the kappa concordance test. RESULTS: According to pulsed duplex ultrasound, 54 patients presented veno-occlusive incompetence. According to cavernometry, 56 patients presented veno-occlusive incompetence. The concordance between the results of the two examinations was only moderate (kappa = 0.52, p < 0.0001, 95% CI: 0.5886-0.7967). CONCLUSION: Duplex ultrasound is a first-line examination in a case of suspected organic erectile dysfunction due to a vascular cause. However, due to the limited concordance for the aetiological diagnosis of veno-occlusive erectile dysfunction between duplex ultrasound and cavernometry, cavernometry is still indicated in highly selected cases such as preoperative work-up.

Humans↗

Sphingosine kinase-1 as a chemotherapy sensor in prostate adenocarcinoma cell and mouse models.

Systemic chemotherapy was considered of modest efficacy in prostate cancer until the recent introduction of taxanes. We took advantage of the known differential effect of camptothecin and docetaxel on human PC-3 and LNCaP prostate cancer cells to determine their effect on sphingosine kinase-1 (SphK1) activity and subsequent ceramide/sphingosine 1-phosphate (S1P) balance in relation with cell survival. In vitro, docetaxel and camptothecin induced strong inhibition of SphK1 and elevation of the ceramide/S1P ratio only in cell lines sensitive to these drugs. SphK1 overexpression in both cell lines impaired the efficacy of chemotherapy by decreasing the ceramide/S1P ratio. Alternatively, silencing SphK1 by RNA interference or pharmacologic inhibition induced apoptosis coupled with ceramide elevation and loss of S1P. The differential effect of both chemotherapeutics was confirmed in an orthotopic PC-3/green fluorescent protein model established in nude mice. Docetaxel induced a stronger SphK1 inhibition and ceramide/S1P ratio elevation than camptothecin. This was accompanied by a smaller tumor volume and the reduced occurrence and number of metastases. SphK1-overexpressing PC-3 cells implanted in animals developed remarkably larger tumors and resistance to docetaxel treatment. These results provide the first in vivo demonstration of SphK1 as a sensor of chemotherapy.

Adenocarcinoma↗

High prevalence of erectile dysfunction in young male patients after intramedullary femoral nailing.

OBJECTIVES: To evaluate, given the central role of the pudendal nerves in erection, the impact of potential infraclinical lesions on male sexual function. After intramedullary femoral fixation, countertraction on the fracture table has sporadically been involved in pudendal neurapraxia. Patients with tibial fractures served as controls. METHODS: A total of 168 patients treated for femoral or tibial shaft fractures by intramedullary nailing were mailed the International Index of Erectile Function questionnaire, which addresses all aspects of male sexual function and permits grading of the severity of erectile dysfunction (ED). Univariate and multivariate analyses were conducted to test for factors associated with ED. RESULTS: Of the 168 patients, 101 (60.1%) returned the questionnaire. A greater proportion of ED was observed in sexually active patients after femoral fracture than after tibial fracture (40.5% versus 12.5%, P <0.01). The differential prevalence of ED in both groups subjected to comparable high-energy trauma suggested that post-traumatic stress disorder was of marginal importance in ED occurring after femoral nailing. Greater intraoperative doses of curare were associated with better sexual functioning in sexually active patients after femoral fracture (10.6 versus 7.5 mg in patients without and with ED, respectively, P = 0.02), suggesting that postoperative ED could be partially prevented by optimal muscle relaxation during fracture reduction. CONCLUSIONS: Erectile dysfunction was shown to be highly prevalent after intramedullary nailing of femoral shaft fractures. Greater intraoperative curare doses, resulting in optimal relaxation and reduced pressure on the pudendal nerves by the perineal post, were associated with better sexual functioning.

Adult↗

[Prospective study of iliac extraction of the kidney after laparoscopic nephrectomy].

INTRODUCTION: Various routes are used to extract the operative specimen during laparoscopic nephrectomy. The main points are compliance with rules of cancer surgery, when applicable, and minimum wall destruction. The objective of this study was to prospectively evaluate the low iliac approach. MATERIAL AND METHOD: Prospective follow-up of 23 laparoscopic nephrectomies (17 tumours and 6 living donor kidney harvestings) in which the kidney was extracted via a low iliac incision measuring 5 to 7 cm. RESULTS: The mean operating time was 188 +/- 50 min with a mean blood loss of 112 +/- 126 ml. The mean duration of the incision was 10 minutes. In the case of a tumour the mean weight of the operative specimen was 571 +/- 127 g in and the mean diameter of the mass was 5.7 +/- 1.9 cm. All grafted kidneys functioned normally. No surgical conversion was necessary. The mean follow-up was 9.6 +/- 1.2 months. No late postoperative complications were observed. CONCLUSION: Radical nephrectomy or living donor kidney harvesting can be performed via laparoscopy with extraction of the operative specimen via a low iliac incision. This incision ensures extraction of very large specimens while preserving the aesthetic and functional advantages of laparoscopy with no increased cancer risk. They are simple to perform and easily reproducible via a transperitoneal or retroperitoneal approach. Absence of muscle section maintains the integrity of the abdominal wall. No postoperative incisional hernia has been observed.

Female↗

Three-dimensional conformal radiotherapy for localized prostate cancer in kidney transplant recipients.

BACKGROUND: This is the first report of graft function and prostate cancer control in renal transplant recipients subjected to modern conformal radiotherapy. METHODS: Eight kidney transplant recipients were treated with three-dimensional conformal radiotherapy. All patients but one were subjected to transitory hormonal deprivation. A three-dimensional radiotherapy-planning system (Pinnacle, Philips Medical System, Bothell, WA) was used to delineate anatomic contours on pretreatment computed tomography and for dose computation. The clinical target volume encompassed the prostate and was expanded with a 10-mm wide margin in all directions to obtain the planning target volume. The irradiation technique consisted of a nine-field arrangement delivering 70 Gy in 2-Gy fractions, with 18-MV photon beams. Biochemical recurrence was defined as two consecutive increases in prostate-specific antigen (>1.5 ng/mL). Graft function was monitored by creatinine clearance. Excretory profiles were assessed by furosemide-stimulated diethylenetriaminepentaacetic acid renography. All patients were subjected to hip magnetic resonance imaging to assess for avascular hip necrosis. RESULTS: After a mean follow-up of 28 months, two patients showed isolated biochemical recurrence and six patients remained free of recurrence. In seven patients with functional allografts, the creatinine clearance was unimpaired by treatment. However, significant obstruction of the terminal ureter was revealed in two patients by furosemide-stimulated diethylenetriaminepentaacetic acid renograms. The doses delivered to the uretero-neocystostomy were calculated to range from less than 20 Gy to more than 45 Gy depending on bladder repletion. CONCLUSIONS: Adequate cancer control was achieved at the expense of infraclinical ureteral obstruction. The doses delivered to the uretero-neocystostomy may be reduced by having a full bladder at the time of irradiation. No avascular hip necrosis was observed.

Aged↗

Direct FGF receptor 1 activation through an anti-idiotypic strategy mimicks the biological activity of FGF-2 and inhibits the progression of the bladder carcinoma derived from NBT-II cells.

The hypothesis that tumor growth is angiogenesis-dependent has been documented by a considerable body of direct and indirect experimental data. Since the discovery of the vascular endothelial growth factor (VEGF), most attention has been focused on the VEGF system. Although fibroblast growth factors 1 and 2 (FGF-1 and FGF-2) can exert a strong angiogenic activity when they are supplied as a single pharmacological agent, their role in pathological angiogenesis in preclinical models remains controversial. To decipher the contribution of FGF receptors in various models of angiogenesis, we took advantage of the anti-idiotypic strategy to obtain circulating agonists specific for FGFR-1 and FGFR-2 (AIdF-1 and AIdF-2). They mimicked FGF-1 and FGF-2 for receptor binding, signal transduction, proliferation of endothelial cells and differentiation of the bladder carcinoma cell NBT-II which expresses FGFR-2b but not FGFR-1. The constitutive expression of FGFR-1 allowed binding of FGF-2 and AIdF-2 and inhibition of the proliferation of NBT-II cells. AIdF-1 and AIdF-2 induced angiogenesis in the corneal pocket assay. Although FGFR-1 dimerization achieved by AIdF-2 injection led to highly differentiated and smaller NBT-II tumors, no sign of reduction of tumor angiogenesis was observed, thus suggesting that endothelial cells are resistant to FGF.

Adrenal Cortex↗

T1G3 bladder tumours: the case for radical cystectomy.

INTRODUCTION: Many factors degrade the initially favourable results of conservative treatment of T1G3 bladder tumours, leading to a permanent risk of progression and death. On the other hand, immediate radical cystectomy, while ensuring optimal local control of the disease, would be excessive in some patients in part because of its purported impact on quality of life. METHODS: To contribute to the ongoing debate on T1G3 optimal treatment the literature was reviewed to organize evidences in favour of radical cystectomy by focusing on two main issues: the impact of time on the initial results of conservative treatment and quality of life after cystectomy. RESULTS: A critical appraisal of conservative treatment efficacy was structured by comparing survival curves after either conservative treatment or radical cystectomy. It highlighted that after conservative treatment the patients remained under the burden of lifelong risk of progression and death. The positive impact of maintenance BCG and the frequent resort to cystectomy after conservative treatment further illustrated the limits of bladder conservative treatments. On the other hand, evidences were shown that quality of life was not critically affected by radical cystectomy and that surgical techniques could be further adapted to its preservation. The influence of age at cystectomy on functional results was highlighted. However, identifying a prognostic factor for the success of conservative treatment would put an end to the controversy by allowing a tailored attitude to every patient's unique situation. The importance of uropathologist's expert evaluation, including the depth of invasion, was emphasized. CONCLUSION: While ensuring optimal control of the disease, the indiscriminate use of radical surgery would be excessive in a significant minority of patients who do well under conservative treatment. It is suggested to consider as typical cases for immediate surgery, young patients with "deep" T1 tumours (>T1a or >1.5mm in depth) with at least one additional factors of bad prognosis: multifocality, association of carcinoma-in-situ, prostatic involvement, site difficult to resect.

Cystectomy↗

Long-term efficacy of two cycles of BEP regimen in high-risk stage I nonseminomatous testicular germ cell tumors with embryonal carcinoma and/or vascular invasion.

OBJECTIVES: To report the long-term impact of two cycles of adjuvant chemotherapy on relapse rates and treatment-related morbidity in high-risk stage I nonseminomatous testicular germ cell tumors (NSGCTT I). MATERIAL AND METHODS: From April 1987 to September 1997, 40 stage I NSGCTT patients with evidence of vascular invasion and/or embryonal carcinoma (EC) in the orchidectomy specimen were treated with two courses of bleomycin, cisplatin, and etoposide (BEP). RESULTS: All patients but one (incidental death) were alive after an extended follow-up (median 113.2 months, range 63-189). No patients relapsed but two patients presented a second cancer in the remaining testis. Short-term toxicity was minimal and no long-term toxicity was observed. CONCLUSION: The present series, with extensive follow-up, demonstrated that the efficacy and toxicity of two cycles of BEP compared well with the results of surveillance strategies or RPLND in high-risk stage I NSGCTT.

Adolescent↗

Efficacy of paclitaxel released from bio-adhesive polymer microspheres on model superficial bladder cancer.

PURPOSE: We aimed to promote the efficacy of paclitaxel in intracavitary treatment of superficial transitional cell carcinoma of the bladder by designing bio-adhesive microspheres capable of achieving controlled release of the drug at the urothelium/urine interface. MATERIALS AND METHODS: Poly(methylidene malonate 2.1.2) microspheres encapsulating paclitaxel were prepared by a single emulsion method. Bioactivity of the released paclitaxel was confirmed by assessing cytotoxicity on MBT-2, a bladder cancer cell line. Biodistribution of particles after bladder instillation was assessed by confocal microscopy and scanning electron microscopy. In vivo studies were performed in Balb/c mice after bladder cancer was induced by BBN (N-n-Butyl-N-butan-4-ol-nitrosamine) in drinking water. The efficacy of intravesical injections of conventional and microsphere paclitaxel was assessed by histology and survival rates. RESULTS: Spherical 5 microm microspheres with 5% weight per weight paclitaxel loading ensured sustained release of bioactive paclitaxel. After bladder instillation the microspheres adhered to the mucosa and remained in the bladder lumen for at least 48 hours. In the BBN induced bladder cancer model compared with controls the 9-week survival rate was significantly improved by 2 injections of paclitaxel bio-adhesive microparticles. Microscopic evaluation confirmed the lower incidence of carcinoma in situ and high grade transitional cell carcinoma after injections of paclitaxel bio-adhesive microparticles compared with controls and with injections of similar doses of the conventional paclitaxel formulation. CONCLUSIONS: Intravesical administration of poly(methylidene malonate 2.1.2) paclitaxel microspheres is a promising approach for intracavitary chemotherapy of superficial bladder cancer.

Adhesives↗