Gilles Karsenty

FGFR1 and WT1 are markers of human prostate cancer progression.

BackgroundAndrogen-independent prostate adenocarcinomas are responsible for about 6% of overall cancer deaths in men.MethodsWe used DNA microarrays to identify genes related to the transition between androgen-dependent and androgen-independent stages in the LuCaP 23.1 xenograft model of prostate adenocarcinoma. The expression of the proteins encoded by these genes was then assessed by immunohistochemistry on tissue microarrays (TMA) including human prostate carcinoma samples issued from 85 patients who had undergone radical prostatectomy.ResultsFGFR1, TACC1 and WT1 gene expression levels were associated with the androgen-independent stage in xenografts and human prostate carcinoma samples. MART1 protein expression was correlated with pT2 tumor stages.ConclusionOur results suggest that each of these four genes may play a role, or at least reflect a stage of prostate carcinoma growth/development/progression.

Botulinum toxin type A inhibits the growth of LNCaP human prostate cancer cells in vitro and in vivo.

Botulinum toxin type A (BTA) intraprostatic injection induces an improvement of urinary symptoms related to benign prostatic hypertrophy (BPH). Infra‐clinical prostate cancer (PCa) foci and pre‐neoplasic lesions occur concomitantly with BPH in a significant number of patients. The objective of this study was to address whether BTA influences the growth of prostate tumors.

Molecular analysis integrating different pathways associated with androgen-independent progression in LuCaP 23.1 xenograft

After therapeutic hormone deprivation, most prostate cancer (PrCa) cells develop androgen-independent (AI) growth. PrCa is highly heterogeneous and multifocal, suggesting that several molecular processes or pathways may be contributing to AI. The human LuCaP 23.1 xenograft model retains clinical hallmarks of PrCa, including heterogeneous growth, PSA production, androgen-responsiveness and progression to AI. In this work, we studied the effect of androgen depletion (castration) on the growth of LuCaP 23.1 xenografts. A total of 100 nude mice were implanted and analysed for their growth profiles before and after castration. By 11 and 15 weeks, tumours were harvested and assessed for molecular marker expression specific for PrCa. Prior to castration we found 37 fast growing (FG) tumours (948.9±76.9 mm3) and 63 slow growing (SG) tumours (229.6±18.4 mm3), a previously undescribed result for this PrCa model. Quantitative RT–PCR showed that in comparison to SGs, FGs contained high HER1, uPA and thymidilate synthetase (TS) expression with low levels of 5α-reductase 2 mRNA. All FG tumours progressed rapidly to AI growth 5 weeks after castration (FG-P). In SG castrated tumours, 66% of tumours (SG-P) showed retarded progression (by 12 weeks) to AI, whereas 34% responded to castration (SG-R). Molecular analysis permitted us to define distinct molecular profiles integrating different pathways associated with AI progression. FG-P, and a subgroup of SG-P tumours, presented significantly high levels of peptidylglycine α-amidating monooxygenase (PAM), HER1, HER2, TS, and uPA mRNA, all of which correlated with AR expression. The second subgroup of SG-P tumours showed overexpression of the antiapoptotic gene Bcl-2. A third subgroup of SG-P tumours showed significant expression of hypoxia-related gene (adrenomedullin) after castration. This work permitted to define distinct molecular profiles related to different AI growth in the LuCaP 23.1 xenograft.

Severe soft tissue infection of the thigh after vaginal erosion of transobturator tape for stress urinary incontinence

Since the beginning of use of synthetic midurethral slings, several complications, usually benign, have been reported. Recently, three consecutive cases of severe thigh infection secondary to transobturator insertion of a synthetic tape alarmed us. This is a case report about these three cases and a review of literature about complications of transobturator tapes.

Effect of Antiepileptic Agent, Levetiracetam, on Urodynamic Parameters and Neurogenic Bladder Overactivity in Chronically Paraplegic Rats

OBJECTIVES To investigate the effects of different levetiracetam (LEV) doses on urodynamic parameters in an animal model of neurogenic detrusor overactivity (NDO). METHODS A total of 54 female rats were studied. Of the 54 rats, 6 served as normal controls, and 48 underwent T10 spinal cord transection (SCT). Of the latter 48 rats, 12 were paraplegic controls, and the remaining 36 rats were divided into 3 equal subgroups that received LEV by way of a subcutaneous osmotic minipump at a dose of 17, 54, and 108 mg/kg daily, respectively. The paraplegic control and treatment groups were further subdivided (n = 6), and cystometry was performed at 3 and 4 weeks after SCT, respectively. RESULTS All paraplegic controls developed NDO, with spontaneous contractions. At 3 and 4 weeks after SCT, the mean frequency of the contractions was 1.6 +/- 0.3/min and 1.7 +/- 0.2/min. The contraction amplitude and bladder capacity were not significantly different. After 1 week of LEV treatment, these urodynamic parameters improved significantly in a dose-dependent manner, and the changes were more striking at 2 weeks. At a LEV dosage of 17, 54, and 108 mg/kg, respectively, the NDO frequency increased from 1.7 +/- 0.3 to 0.7 +/- 0.2 contractions/min (P = .01), 0.48 +/- 0.16 contractions/min (P = .009), and 0.5 +/- 0.17 contractions/min (P = .01). The bladder capacity increased from 0.51 +/- 0.1 mL to 1.5 +/- 0.2 mL (P = .0001), 2.5 +/- 1.7 mL (P = .006), and 2.6 +/- 0.3 mL (P = .0003), and the micturition pressure improved from 105.8 +/- 6.9 to 73.8 +/- 6.8 cm H(2)O (P = .01), 58.6 +/- 8.9 cm H(2)O (P = .006), and 49.7 +/- 8.9 cm H(2)O (P = .002). CONCLUSIONS The results of our study have shown that LEV is an effective treatment of NDO after SCT in rats. It might prove to be a novel, alternative therapeutic approach to NDO. The follow-up of these experimental results with a clinical trial is warranted.

P-Mate™, a new device allowing women to urinate in the standing position: urodynamic and satisfaction assessment

Urodynamic parameters and satisfaction were recorded after micturition in the seated position versus the standing position with a single-use device (P-Mate™) in healthy women. Healthy adult women were recruited. Eligibility criteria were: no past urological history and no urological symptoms. Volunteers were given four P-Mates™ to use during a week and a satisfaction questionnaire to fill. After this trial week, they were invited to perform four flowmetries, two in the seated position and two standing up, with the P-Mate™. Seated and standing flowmetry parameters were compared (by paired t-test). Twenty women completed the study. There was no difference in the maximum flow rate (Qmax), voided volume and post-void residual (PVR) in the standing versus the seated position. In terms of Qmax and PVR in healthy women, urinating standing up was as efficient as in the seated position. A majority of participants were satisfied with the device.

Traumatisme de la verge et des organes génitaux

RésuméLes traumatismes testiculaires sont le plus souvent des traumatismes fermés rencontrés lors d’accidents de la voie publique ou de sport. Un gros testicule douloureux dans ce contexte fait poser le diagnostic et l’échographie oriente la thérapeutique vers la chirurgie en cas de rupture de l’albuginée ou de gros hématome intra testiculaire. Deux patients sur trois seront opérés et les principales séquelles rencontrées en cas de diagnostic et traitements tardifs sont l’atrophie testiculaire, la stérilité voire l’impuissance.Les fractures du pénis sont secondaires à un traumatisme direct sur le pénis en érection avec rupture de l’albuginée et entraînent hématome, douleur et déviation pénienne. Une plaie urétrale doit être systématiquement recherchée. Cavernographie, échographie ou IRM peuvent aider au diagnostic sans être systématiques. Le traitement de référence est chirurgical précoce et les complications possibles sont les déviations péniennes, douleurs, dysfonction érectile.AbstractThe most frequent cause of testicular injuries is blunt trauma (following sports injuries or road accidents). Penetrating injuries are rare. Increased scrotal volume and a painful testis are the main symptoms and require scrotal ultrasonography. Scrotal ultrasonography is very sensitive and specific for testicular rupture or intratesticular haematoma. Two out of three patients with testicular injuries require surgical exploration. Secondary complications due to delayed management of trauma are testicular atrophy, sterility or impotence.Penile fracture (rupture of corpus cavernosum) is due to direct trauma by an excessive force applied to an erect penis. Swelling, penile ecchymosis, penile curvature and pain are the usual symptoms of rupture of the tunica albuginea. Urethral injury must be ruled out. Cavernosography, ultrasonography or MRI are not considered mandatory to establish a diagnosis but can be prescribed in the absence of typical signs or symptoms. Early surgical exploration and repair ensure a better outcome. Secondary complications are penile curvature, chronic pain and impotence.