Surgical Treatments of Benign Prostatic Hyperplasia and Prostate Cancer Stereotactic Radiotherapy: Impact on Long-Term Genitourinary Toxicity.

AIMS: Although the results on acute and late toxicity of ultrahypofractionation are encouraging, data on safety in prostate cancer patients with a medical history of transurethral resection of the prostate (TURP) or adenomectomy remain scarce, especially in cases of repeated procedures. The aim of the present study was to report on long-term toxicities after stereotactic body radiotherapy (SBRT) of prostate cancer patients with previous surgical treatment of benign prostatic hyperplasia. MATERIALS AND METHODS: Among 150 patients treated with SBRT (median dose 36.25 Gy in five fractions) realised from 2014 to 2019 in a single-centre institution, data of 24 men with a history of TURP (n = 19) or adenomectomy (n = 5) were analysed. Repeated TURP was carried out in three patients, with a median time between surgery and SBRT of 54 months. Genitourinary toxicity was assessed using the Common Terminology Criteria for Adverse Events v4.0 grading scale. RESULTS: With a median follow-up of 45 months, 10 of 24 (42%) patients experienced at least one episode of transient haematuria. One patient (4%) with three previous TURP presented a grade 3 acute non-infective cystitis. Late grade 2 and 3 genitourinary toxicities were observed in eight (33%) and four patients (17%) (two treated with adenomectomy, one with multiple TURP and one with a 140 cm3 prostate size), respectively, with no grade ≥4 adverse events. A complete recovery of grade 3 genitourinary toxicities was observed for all patients after hyperbaric oxygen therapy. CONCLUSION: Prostate SBRT is feasible and well-tolerated in patients with a medical history of surgical treatments of benign hyperplasia. Patients with prior adenomectomy or multiple TURP are at higher risk of developing severe genitourinary toxicity and should be carefully evaluated before SBRT treatments.

Ultrahypofractionated Radiotherapy for Localised Prostate Cancer: How Far Can We Go?

Following adoption of moderately hypofractionated radiotherapy as a standard for localised prostate cancer, ultrahypofractioned radiotherapy delivered in five to seven fractions is rapidly being embraced by clinical practice and international guidelines. However, the question remains: how low can we go? Can radiotherapy for prostate cancer be delivered in fewer than five fractions? The current review summarises the evidence that radiotherapy for localised prostate cancer can be safely and effectively delivered in fewer than five fractions using high dose rate brachytherapy or stereotactic body radiotherapy. We also discuss important lessons learned from the single-fraction high dose rate brachytherapy experience.

[Association between sperm abnormalities and occupational environment among male consulting for couple infertility]. / Association entre anomalies spermatiques et environnement professionnel chez les hommes consultant pour infertilité de couple.

Alteration of sperm parameters related to occupational exposures is the subject of several studies, often on a case-control approach. The study populations usually comprise men consulting in infertility clinics for couple infertility. The objective of this review is to identify, from these case-control studies, the main occupational factors that may be associated with altered sperm parameters. We selected 13 articles in the PubMed database. Participation in these studies varied from 61 to 2619 subjects, with great methodological heterogeneity, particularly in the characterization of exposure. The main occupations that appear significantly associated with a risk of altered sperm parameters are workmen, painters, farmers, welders, plumbers and technicians. When analysis focuses on occupational exposures, a significant result is reported for solvents, heavy metals, heat, vibrations and non-ionizing radiation. None of the selected studies has found a link with exposure to pesticides.

[Elective single embryo transfer policy at 48/72 h: which results after fresh transfers and frozen/thawed transfers?]. / Politique de transfert électif d'un embryon à 48/72h: quels résultats après transferts frais et transferts d'embryons congelés ?

OBJECTIVES: To evaluate our elective single embryo transfer policy performed at 48/72h and define predictive factors of pregnancy after frozen/thawed embryo transfer. METHODS: Analysis of 289 elective single embryo transfers (eSET) performed in a selected population in the ART center of Marseille University Hospital from January 2005 to December 2011, as well as the 325 following frozen/thawed embryo transfers performed in this population between May 2005 and December 2012. RESULTS: Cumulative pregnancy rate/oocyte retrieval was of 62.6%; 45% of the couples obtained the birth of at least one child. During this studied period, cumulative pregnancy and delivery rates in the whole population remained stable while multiple delivery rate/delivery clearly decreased. Elective single embryo after frozen/thawed transfer gave satisfying results (24.6% pregnancy/transfer) only in the lack of lysis or in case of mild lysis (1-25%) of the transferred embryo. CONCLUSION: The implementation of an eSET policy gives satisfying results, depending largely on embryo quality. By proposing eSET to a well-targeted population, chosen both on clinical and biological criteria, a clear reduction of cumulative multiple delivery rate/delivery was obtained in our center over this period, without any global decrease of cumulative pregnancy rate/attempt. Embryo quality is a major factor of success, especially in frozen/thawed cycles. The elective single embryo frozen/thawed transfer should be carried out only if embryo lysis after thawing does not exceed 25%.

Glucocorticoid receptors in human epicardial adipose tissue: role of coronary status.

BACKGROUND: Epicardial adipose tissue (EAT) is in close contact with coronary vessels and therefore could alter coronary homeostasis. Glucocorticoids are pathophysiological mediators of visceral fat deposition and its associated atherogenic complications. AIM: We investigated in EAT the expression of the glucocorticoid receptor (GR) and its various (A, B, C) promoters. MATERIALS AND METHODS: Paired subcutaneous adipose tissue (SAT) and EAT biopsies were obtained from 15 patients with coronary artery disease (CAD) and 12 patients without CAD (NCAD). GR and 11ß-hydroxysteroid dehydrogenase type 1 protein (11ß-HSD-1, the enzyme which converts inactive cortisone into active cortisol) were studied by immunohistochemistry and GR and its various promoters were studied by mRNA quantitative RT-PCR. RESULTS: GR and 11ß-HSD-1 protein were expressed in adipocytes, stromal areas, isolated stromal cells close to adipocytes, and blood vessels. Total GR mRNA levels did not differ in SAT obtained from NCAD or CAD patients and were decreased in EAT, irrespectively of the coronary status, with parallel changes in promoter B- and C-, but not promoter A-associated transcripts. Total GR mRNA and adipocyte surface in EAT obtained from CAD patients were correlated negatively (p<0.035, r=0.39). CONCLUSIONS: Our findings demonstrate that in EAT, GR gene promoters could play a role in tissue- specific GR expression levels. EAT may be less sensitive to glucocorticoids than SAT, preventing the EAT mass development in CAD patients and suggesting a protective role on coronary homeostasis.

Expression and nutritional regulation of the (pro)renin receptor in rat visceral adipose tissue.

BACKGROUND: Early life nutritional environment plays an important role in the development of visceral adipose tissue and interacts with nutritional regulations in adulthood, leading to metabolic dysregulations. AIM: We hypothesized that the renin-angiotensin system may play a role in the programming-induced development of visceral adipose tissue. MATERIAL AND METHODS: We studied, using a model of programming of overweight and glucose intolerance, obtained by post-natal overfeeding with consecutive highfat diet, the status of plasma renin activity and mesenteric adipose renin-angiotensin system, including the recently identified (pro)renin receptor, in adult rats. RESULTS: Post-natal overfeeding or high-fat feeding lead to overweight with increased visceral fat mass and adipocytes surface. When both paradigms were associated, adipocytes surface showed a disproportionate increase. A strong immunoreactivity for (pro)renin receptor was found in stromal cells. Plasma renin activity increased in programmed animals whereas (pro)renin receptor expressing cells density was stimulated by high-fat diet. There was a positive, linear relationship between plasma renin activity and (pro)renin receptor expressing cells density and adipocytes surface. CONCLUSIONS: Our experiments demonstrate that association of post-natal overfeeding and high-fat diet increased plasma renin activity and adipose (pro)renin receptor expression. Such phenomenon could explain, at least in part, the associated disproportionate adipocyte hypertrophy and its accompanying increased glucose intolerance.

[Macrocephalic spermatozoa. What would be the impact on reproduction?]. / Les spermatozoïdes macrocéphales. Quels risques pour la fonction de reproduction ?

OBJECTIVE: We want to highlight the risk of infertility and failure of Assisted Reproductive Technologies due to the presence of macrocephalic spermatozoa (MS) in the sperm at rate equalling or superior to 20% in at least one semen analysis. PATIENTS AND METHODS: We did a retrospective analysis of 19 infertile patients presenting MS at average rate between 14.3 and 49.7%. For each patient, at least one semen analysis showed a MS rate equal or superior to 20%. We did an automated analysis of the spermatozoa surface for 13 patients and a detailed analysis of the MS morphology in 18 patients. Thirteen couples benefited of one or more IVF with or without ICSI. RESULTS: The semen analysis shows an impairment of one or more parameter of the sperm in all patients. Three morphological aspects for MS were highlighted: MS with irregular head, MS with regular head, and MS with multiple heads, with a dominance of irregular heads. The spermatozoa surface analysis shows a significant increase of the average surface and of the standard deviation (p<0.0001). The average rate of pregnancies by transfer is decreased compared to usual rates in our laboratories (13% versus 28%). DISCUSSION AND CONCLUSION: We want to sensitize biologist and clinical doctors to the existence of partial forms of this syndrome, which could be related to infertility with impaired sperm parameters and low pregnancy rates after FIV or ICSI.

[Genetic aspects of the teratozoospermia]. / Aspects génétiques de la tératozoospermie.

Recent mutation identification in well-known sperm defects gives proof that there are genetic causes of infertility. Familial forms and some features of the spermograms lead toward the genetic origin of these syndromes. For each syndrome, several clinical aspects and partial forms were described. In these latter, apparently normal spermatozoa coexist with those showing the phenotype of interest. Transmission electron microscopy is the better tool to characterize the specific details of each syndrome. The frequency of genetic teratozoospermia is weak, the most studied syndromes are the globozoospermia, the macrocephaly, the syndrome of decapitated spermatozoa and the dyplasia of the fibrous sheat. A mutation was identified for two from these syndromes, but the two mutations does not account for all the cases from each syndrome. The various clinical aspects observed for each syndrome suggest that either other mutations or other genes are probably involved in these spermatogenic failures. The use of spermatozoa from patients for intra cytoplasmic sperm injection (ICSI) may pose two problems: fertilization problems and genetic risk for the progeny, including chromosomic and genic risk. Except for total macrocephaly which is excluded from ICSI because of sperm chromosomal abnormalities, these syndromes are consistent with assisted fertilization, but with uncertain rates of fertilization and pregnancy.

Effect of sleep apnea syndrome on the circadian profile of cortisol in obese men.

It has been hypothesized that sleep apnea syndrome (SAS) increases hypothalamic-pituitary-adrenal axis activity and, through increased cortisol levels, participates in the pathophysiology of metabolic and cardiovascular complications. We compared the circadian profiles of cortisol in obese men with [obSAS+; apnea-hypopnea index (AHI) >or= 20/h] and without SAS (obSAS-; AHI

Expression of adrenomedullin in adipose tissue of lean and obese women.

OBJECTIVE: Adrenomedullin (AM), a potent vasodilatator and antioxidative peptide, was shown recently to be expressed by adipose tissue. The aim of our study was to investigate the precise localization of AM within human adipose tissue, and to examine AM regulation in obesity. DESIGN: Subcutaneous (SC) and omental (OM) adipose tissues from 9 lean and 13 obese women were profiled for AM expression changes. Preadipocytes from human adipose tissue were isolated and differentiated under defined adipogenic conditions. METHODS: AM expression was analyzed by immunohistochemistry, in situ hybridization and quantitative RT-PCR. RESULTS: A strong AM expression was observed in vessel walls, stromal cell clusters and isolated stromal cells, some of them being CD 68 positive, whereas mature adipocytes were not labeled. Calcitonin receptor-like receptor and receptor activity-modifying proteins (RAMP) 2 and RAMP 3 were expressed in vessel walls. In vitro, preadipocytes of early differentiation stages spontaneously secreted AM. No difference in AM localization was found between SC and OM adipose tissue. AM levels in SC tissue did not differ between lean and obese subjects. By contrast, AM levels in OM tissue were significantly higher in obese as compared with lean women. Moreover, we found a positive relationship between OM AM and tumor necrosis factor alpha mRNA levels and AM-immunoreactive area in OM tissue followed the features of the metabolic syndrome. CONCLUSION: Stromal cells from human adipose tissue, including macrophages, produce AM. Its synthesis increased in the OM territory during obesity and paralleled the features of the metabolic syndrome. Therefore, AM should be considered as a new member of the adipokine family.

[Optimization of artificial inseminations with donor semen: a four-year experience]. / Optimisation des résultats d'inséminations intra-utérines uniques avec sperme de donneur: bilan de quatre ans d'activité.

OBJECTIVE: Our aim was to analyse the results of a donor insemination program using ovarian stimulation, swim-up sperm preparation and intrauterine insemination proposed to women with a maximum age of 39. Incidence of several clinical and biological parameters on success rates was investigated. PATIENTS AND METHODS: Retrospective analysis of the results of 249 cycles performed in 106 couples during a four-year period is reported. RESULTS: Overall pregnancy rate of 28.1% and delivery rate of 22% per cycle were achieved, with a multiple pregnancy rate of 11.4%. Most of the pregnancies (84%) were obtained before the fourth insemination. Among the different parameters studied the total number of motile sperm inseminated was found to be the most important factor for success rate: pregnancy rate per cycle reached 40.4% if more than 1.5 million progressive sperm were inseminated vs. 24.7% if they were less than 1.5 million (P<0.05). DISCUSSION AND CONCLUSION: In precise conditions, outcome of inseminations with donor semen can reach satisfying pregnancy rates, being a valuable help for couples suffering of long-time infertility.

Pregnancies after ICSI using sperm with abnormal head-tail junction from two brothers: case report.

We report ICSI pregnancies in two couples with a history of long standing primary infertility in which the sperm of the male partner were either acephalic or had abnormal head-midpiece attachments. The two couples, in which the men are brothers, underwent ICSI. Sperm were analysed by transmission electron microscopy and immunocytochemistry with an anti-MPM2 monoclonal antibody. The first couple underwent two ICSI cycles, each consisting of the injection of two mature oocytes and the transfer of two embryos. A successful pregnancy occurred after the second transfer and led to the birth to a healthy girl. The second couple underwent three ICSI cycles, each consisting of the injection of 18 oocytes and the transfer of two embryos; the last of these led to a triple ongoing pregnancy which included two identical twins. Caesarean section led to the birth of three fetal-growth restricted children. This case report demonstrates that ongoing pregnancies can be achieved in cases of abnormal development of the head-neck attachment. The genetic origin of this syndrome is generally accepted, but the phenotypic heterogeneity observed by light and electron microscopy among published cases suggests that there are a variety of genetic causes of this syndrome.