Hypospadias: conséquences psychosociales, urologiques, sexuelles et reproductives à l’âge adulte

Hypospadias is a developmental abnormality. The most obvious feature is an ectopic urethral meatus situated on the ventral aspect of the glans or the penis, or on the scrotum or perineum. This defect occurs in about 1/250 to 1/300 live births. Surgical repair is designed to allow micturition in a standing position, enable normal sexual function and to give the penis as normal a cosmetic appearance as possible. This malformation and its treatment have repercussions on psychosocial development, urinary and sexual function, and reproduction. The literature distinguishes three populations of patients.

1. Patients who have corrective surgery during childhood. The most frequent urological complications are fistulas, diverticula, urethral stenosis and micturition difficulties. The risk of infection is not increased. Psychosocial development is usually not affected, and maturation and early sexual awareness are normal. However, these patients have greater difficulty in making contact with the opposite sex. In adulthood, problems of erection and ejaculation are frequent.
2. Patients who have corrective surgery in adulthood. The urological results of surgery are less favourables and complications are more frequent than in children. No data about sexual function are available.
3. Patients who do not have surgery. Although there are no specific studies, these patients do not appear to differ from those operated as children in terms of micturition difficulties, psychosexual development and sexual function.
4. Reproductive capacity. There is usually no disorder of the hormones involved in testicular function (gonadotropins, androgens) in either children or adults. However, clinical, histological and spermiological factors may affect fertility.

The frequency of infertility in the population of men who have undergone corrective surgery for hypospadias during childhood has not yet been evaluated.     

Activation of Cdk2 stimulates proteasome-dependent truncation of tyrosine phosphatase SHP-1 in human proliferating intestinal epithelial cells

SHP-1 is expressed in the nuclei of intestinal epithelial cells (IECs). Increased SHP-1 expression and phosphatase activity coincide with cell cycle arrest and differentiation in these cells. Suspecting the tumor-suppressive properties of SHP-1, a yeast two-hybrid screen of an IEC cDNA library was conducted using the full-length SHP-1 as bait. Characterization of many positive clones revealed sequences identical to a segment of the Cdk2 cDNA sequence. Interaction between SHP-1 and Cdk2 was confirmed by co-immunoprecipitations whereby co-precipitated Cdk2 phosphorylated SHP-1 protein. Inhibition of Cdk2 (roscovitine) or proteasome (MG132) was associated with an enhanced nuclear punctuate distribution of SHP-1. Double labeling localization studies with signature proteins of subnuclear domains revealed a co-localization between the splicing factor SC35 and SHP-1 in bright nucleoplasmic foci. Using Western blot analyses with the anti-SHP-1 antibody recognizing the C terminus, a lower molecular mass species of 45 kDa was observed in addition to the full-length 64-65-kDa SHP-1 protein. Treatment with MG132 led to an increase in expression of the full-length SHP-1 protein while concomitantly leading to a decrease in the levels of the lower mass 45-kDa molecular species. Further Western blots revealed that the 45-kDa protein corresponds to the C-terminal portion of SHP-1 generated from proteasome activity. Mutational analysis of Tyr(208) and Ser(591) (a Cdk2 phosphorylation site) residues on SHP-1 abolished the expression of the amino-truncated 45-kDa SHP-1 protein. In conclusion, our results indicate that Cdk2-associated complexes, by targeting SHP-1 for proteolysis, counteract the ability of SHP-1 to block cell cycle progression of IECs.     

Evaluation of sexual functions and sexual behaviors after penile brachytherapy in men treated for penile carcinoma

Purpose

To assess sexual functions and behaviors of men treated by penile brachytherapy for a cancer of the penis.

Materials and methods

Thirty eight men (19 patients treated by penile brachytherapy for a cancer of the penis and 19 age paired-matched controls) participated in a survey about sexuality. The mean age of patients and controls were 73.2 +/- 11.7 and 70.0 +/- 10.5 years, respectively (NS). Controls were men without penile pathology, without history of cancer and no evidence of cognitive impairment. All agreed to participate in the survey about sexuality using 2 questionnaires : the IIEF questionnaire, which explores 4 domains of sexual functions, namely erection, satisfaction, orgasm and desire, and a questionnaire created using the BASIC IDEA grid, which addresses nine domains: behavior, affect, sensation, self-image, cognition, interpersonal, drugs, expectation and attitude.

Results

Patients had better scores than controls in 3 domains of the IIEF: erection, desire and satisfaction. These results contrasted with the frequency of intercourse and the quality of erection (evaluated through the BASIC IDEA questionnaire) that were not significantly different between the two populations. Patients also had significantly higher frequency of masturbation (p <0.001) lower worry about sexual performance and higher expected satisfaction for future life (p: 0.021) than controls.

Conclusion

Penile brachytherapy is a treatment of cancer of the penis that seems to have a moderated impact on sexual functions since most of sexual scores are not inferior in these patients than in age pair-matched controls.

     

Differential reactivity of human lymphocytes allosensitized in vitro in hormonally defined medium or medium supplemented with plasma

We compared the in vitro allogeneic response of human lymphocytes cultured in hormonally defined medium (HDM) with that of those cultured in plasma-containing medium (PCM). Differences occurred only in secondary MLR or PLT and in cell-mediated cytotoxicity in terms of specificity, which was either greater or modified when HDM was used.     

Subinguinal microsurgical varicocelectomy vs. percutaneous embolization in infertile men: Prospective comparison of reproductive and functional outcomes

Background

Varicocele is a condition characterized by dilated, tortuous veins within the pampiniform venous plexus of the scrotal sac. Presence of varicocele is associated with an increased risk of alteration of semen parameters. The objective of this study was to compare the current standard in varicocele treatment procedures: sub-inguinal microscopic ligation to percutaneous embolization in terms of semen parameters improvement, fertility, and morbidity at the university hospital of Toulouse (France). Seventy six patients with clinical varicocele, alteration of semen parameters and infertility, underwent either procedure (microsurgery in 49 case performed by a single surgeon and embolization in 27 cases) and were prospectively analyzed. Outcome measures were: semen parameters, spontaneous pregnancies, pain, side effects, recovery time and overall satisfaction. All patients were contacted in January 2015 in order to determine reproductive events.

Results

Preoperatively, there was no difference in clinical and biological items between the two groups. Postoperatively, on the overall population, there was a significant improvement of sperm concentration at 3, 6, 9 and 12 months (p?=?<0.001, <0.001, 0.012, 0.018) and sperm motility at 6 months (p?=?0.002). The sperm concentration was higher at 6 months in the percutaneous embolization group (13.42, vs. 8.1×10⁶/ml; p?=?0.043). With a median follow-up of 4 years, 27 pregnancies occurred (spontaneous pregnancy rate of 35.5%).There was no significant difference between procedures on the sperm quality, pregnancy rate, and the overall satisfaction. Patients undergoing percutaneous embolization reported a faster recovery time (p?=?0.002) and less postoperative pain (p?=?0.007).

Conclusion

Our study shows that percutaneous embolization seems to be an equivalent alternative to sub-inguinal microscopic ligation in term of sperm quality improvement, pregnancy rate, and overall satisfaction with a slight advantage on post-operative morbidity.