PSMA-PET/CT-guided salvage radiotherapy in recurrent or persistent prostate cancer and PSA < 0.2 ng/ml.

PURPOSE The purpose of this retrospective, multicenter study was to assess efficacy of PSMA-PET/CT-guided salvage radiotherapy (sRT) in patients with recurrent or persistent PSA after primary surgery and PSA levels < 0.2 ng/ml. METHODS The study included patients from a pooled cohort (n = 1223) of 11 centers from 6 countries. Patients with PSA levels > 0.2 ng/ml prior to sRT or without sRT to the prostatic fossa were excluded. The primary study endpoint was biochemical recurrence-free survival (BRFS) and BR was defined as PSA nadir after sRT + 0.2 ng/ml. Cox regression analysis was performed to assess the impact of clinical parameters on BRFS. Recurrence patterns after sRT were analyzed. RESULTS The final cohort consisted of 273 patients; 78/273 (28.6%) and 48/273 (17.6%) patients had local or nodal recurrence on PET/CT. The most frequently applied sRT dose to the prostatic fossa was 66-70 Gy (n = 143/273, 52.4%). SRT to pelvic lymphatics was delivered in 87/273 (31.9%) patients and androgen deprivation therapy was given to 36/273 (13.2%) patients. After a median follow-up time of 31.1 months (IQR: 20-44), 60/273 (22%) patients had biochemical recurrence. The 2- and 3-year BRFS was 90.1% and 79.2%, respectively. The presence of seminal vesicle invasion in surgery (p = 0.019) and local recurrences in PET/CT (p = 0.039) had a significant impact on BR in multivariate analysis. In 16 patients, information on recurrence patterns on PSMA-PET/CT after sRT was available and one had recurrent disease inside the RT field. CONCLUSION This multicenter analysis suggests that implementation of PSMA-PET/CT imaging for sRT guidance might be of benefit for patients with very low PSA levels after surgery due to promising BRFS rates and a low number of relapses within the sRT field

11β-HSD1 inhibition in men mitigates prednisolone-induced adverse effects in a proof-of-concept randomised double-blind placebo-controlled trial

Glucocorticoids prescribed to limit inflammation, have significant adverse effects. As 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) regenerates active glucocorticoid, we investigated whether 11β-HSD1 inhibition with AZD4017 could mitigate adverse glucocorticoid effects without compromising their anti-inflammatory actions. We conducted a proof-of-concept, randomized, double-blind, placebo-controlled study at Research Unit, Churchill Hospital, Oxford, UK (NCT03111810). 32 healthy male volunteers were randomized to AZD4017 or placebo, alongside prednisolone treatment. Although the primary endpoint of the study (change in glucose disposal during a two-step hyperinsulinemic, normoglycemic clamp) wasn’t met, hepatic insulin sensitivity worsened in the placebo-treated but not in the AZD4017-treated group. Protective effects of AZD4017 on markers of lipid metabolism and bone turnover were observed. Night-time blood pressure was higher in the placebo-treated but not in the AZD4017-treated group. Urinary (5aTHF+THF)/THE ratio was lower in the AZD4017-treated but remained the same in the placebo-treated group. Most anti-inflammatory actions of prednisolone persisted with AZD4017 co-treatment. Four adverse events were reported with AZD4017 and no serious adverse events. Here we show that co-administration of AZD4017 with prednisolone in men is a potential strategy to limit adverse glucocorticoid effects

BASELLA ALBA (BASELLACEAE) AND MALE REPRODUCTIVE FUNCTION

Hibiscus macranthus and Basella alba leaves are mixed in a remedy given, in western Cameroon, to the new king for some weeks during initiation period to sustain his sexual performance. This plant extracts enhanced blood testosterone level in male rats. They were further studied for androgenic activity since they could be used to alleviate male infertility or to treat androgen deficiency in ageing male. Using rat testis slices, methanol extract of both plants significantly induced testosterone synthesis. In primary Leydig cell cultures of bull and rat, extracts from B. alba significantly enhanced testosterone levels in a dose dependant manner. H. macranthus showed no androgenic activity. Phytochemical screening and HPLC study of B. alba extracts revealed presence of terpenoids, limonoides and coumarins. This extract also modulated aromatase gene activity in Leydig cell cultures. In vivo, methanol extract (1 mg/kg) given to adult male rats significantly increased serum testosterone level after 30 days (

Effect of methanol extract of Basella alba L. (Basellaceae) on the fecundity and testosterone level in male rats exposed to flutamide in utero

International audienceWe evaluated the effect of the methanol extract of Basella alba (MEBa) on testosterone level and fecundity/fertility in male rats exposed in utero to flutamide an androgen receptor antagonist. For this purpose, 1.5- and 2.5 -month-old male rats exposed in utero to flutamide were treated with the MEBa (1 mg kg-1) for 2 and 1 month respectively. Five days before the end of treatment, rats were housed with females to assess their fecundity/fertility. Thereafter, rats were sacrificed and blood collected for the quantification of testosterone. Flutamide-exposed male rats showed a decrease in their ano-genital distance (AGD, P < 0.05) and were infertile. In normal (methylcellulose-exposed) animals, MEBa provoked an increase in testosterone level in 1.5- (P < 0.008) and 2.5 -month-old rats (P < 0.01) concomitantly with the improvement in their fecundity by 25%. In flutamide-exposed male rats, MEBa increased testosterone level in 1.5 -month-old rats (P < 0.001) without any effect on their fecundity; while in 2.5- month-old rats, MEBa did not affect the testosterone level but improved fecundity (by 25%) and fertility (P < 0.001). This study demonstrated the positive effect of MEBa to enhance fecundity/fertility in normal male rats and in rats exposed to the antiandrogen flutamide during their foetal life

Bisphenol A differentially affects male reproductive function biomarkers in a reference population and agro pesticides users from Djutitsa, Cameroon

The consequences of bisphenol A (BPA) exposure on male reproductive function were studied in two populations from Cameroon, farmers using agro pesticides in Djutitsa (rural area) and townsmen in Yaounde (urban area, Centre region). Urinary BPA concentration from all participants was measured, and the values were correlated with biochemical markers of male reproductive function. The data showed that BPA could be detected in 92.6% of urine participants, with an average concentration of 2.18 +/- 1.97 microg/g creatinine but with no significant difference between the urinary BPA concentration from rural and urban populations. From BPA urinary concentration, the BPA average daily intake was estimated to be 0.06 +/- 0.05 mug/kg/day (3.51 microg/day per individual) in the Cameroon population. Interestingly, free and bioavailable testosterone concentrations and estradiol/testosterone ratio correlated with BPA levels in the overall population. When data were analysed according to residence, BPA correlated with total testosterone levels ( r = -0.433) and estradiol/testosterone ratio ( r = 0.338) in the urban residents only, while the rural population exhibited significant increases in sex-hormone-binding globulin with increased BPA exposure. Our data showed that the male Cameroon population is exposed to BPA but that inconstant BPA association to endocrine reproductive markers suggests that other environmental factors in combination with BPA exposure might influence testicular function