Eric Huyghe

Gonadal impact of target of rapamycin inhibitors (sirolimus and everolimus) in male patients: an overview

The immunosuppressive agents target of rapamycin inhibitors (TOR‐I) (sirolimus, and everolimus) have been widely used in kidney transplantation for >10 years. Up to 40% of men receiving a kidney transplant are younger than 50, and fertility as well as erectile function are major concerns. In this review, we provide a synopsis of past studies focusing on gonadal function in men treated with TOR‐I, mainly sirolimus, to establish what impact they have on male gonads, and which pathophysiological pathways are involved. A PubMed search for the years 1990–2006 selected articles that focused on the gonadal impact of TOR‐I. Primary outcome measures were testosterone, follicle‐stimulating hormone (FSH), and luteinizing hormone (LH) levels. Secondary outcome measures were sexual function, fertility status and sperm parameters. Treatment with TOR‐I results in a decrease in testosterone level, and an opposite increase in LH. Moreover, spermatogenesis seems to be disrupted by TOR‐I and FSH levels are increased. Sirolimus and everolimus inhibit the activity of mammalian targets of rapamycin, a serine/threonine kinase involved in numerous cell‐growth processes. Molecular mechanisms of action of TOR‐I on the testis involve inhibition of a stem cell factor/c‐kit‐dependant process in spermatogonia. Preliminary results appear to show that TOR‐I treatment has deleterious actions on the testis and impairs gonadal function after renal transplantation, but the impact of these effects are unknown.

Fertility after testicular cancer treatments: Results of a large multicenter study

Patients with testicular cancer have an excellent survival rate, and fertility is one of the main concerns of survivors. The authors investigated fertility status after treatment for testis cancer in long‐term survivors.

Needs Assessment Survey to Justify Establishing a Reproductive Health Clinic at a Comprehensive Cancer Center

INTRODUCTION Reproductive health problems, including sexual dysfunction and impaired fertility, are distressing and persistent after cancer treatment. However, recent reports suggest that reproductive health remains neglected in oncology settings. AIMS We conducted a survey to ascertain the prevalence of reproductive health problems in men and women treated in a comprehensive cancer center, and to estimate potential usage of clinical services to preserve fertility or to treat postcancer infertility and sexual dysfunction. METHODS We mailed 800 questionnaires to men and women treated for cancer at our institution 1 to 5 years previously. Cancer sites and ages were chosen to maximize the risk of reproductive problems. We stratified the sample by living distance from our institution, to see if travel affected service utlilization. To provide a self-selected sample for comparison, another 200 questionnaires were made available in outpatient areas. MAIN OUTCOME MEASURES Self-report questionnaire. RESULTS The return rate for the combined surveys was 29% for men and 26% for women. Cancer sites for self-selected respondents were almost identical to those in the postal cohort. Prevalence and types of sexual dysfunction were typical for surveys of cancer survivors, with 49% of men reporting new erection problems after cancer treatment and 45% of women noting loss of desire for sex and vaginal dryness. About a third of patients aged less than 50 years would have liked a fertility consultation before cancer treatment. Twenty to thirty percent wanted more information about premature ovarian failure or health risks for their children. Twenty-four percent of men and 21% of women would definitely want to visit a reproductive health clinic in the next year. Factors associated with wanting an appointment included self-selection to complete the survey and, for men, having less education. CONCLUSION It should be feasible to establish a multidisciplinary reproductive health center in a comprehensive cancer center.

Ejaculatory function after permanent 125I prostate brachytherapy for localized prostate cancer.

PURPOSE Ejaculatory function is an underreported aspect of male sexuality in men treated for prostate cancer. We conducted the first detailed analysis of ejaculatory function in patients treated with permanent (125)I prostate brachytherapy for localized prostate cancer. PATIENTS AND METHODS Of 270 sexually active men with localized prostate cancer treated with permanent (125)I prostate brachytherapy, 241 (89%), with a mean age of 65 years (range, 43-80), responded to a mailed questionnaire derived from the Male Sexual Health Questionnaire regarding ejaculatory function. Five aspects of ejaculatory function were examined: frequency, volume, dry ejaculation, pleasure, and pain. RESULTS Of the 241 sexually active men, 81.3% had conserved ejaculatory function after prostate brachytherapy; however, the number of patients with rare/absent ejaculatory function was double the pretreatment number (p < .0001). The latter finding was correlated with age (p < .001) and the preimplant International Index of Erectile Function score (p < .001). However, 84.9% of patients with maintained ejaculatory function after implantation reported a reduced volume of ejaculate compared with 26.9% before (p < .001), with dry ejaculation accounting for 18.7% of these cases. After treatment, 30.3% of the patients experienced painful ejaculation compared with 12.9% before (p = .0001), and this was associated with a greater number of implanted needles (p = .021) and the existence of painful ejaculation before implantation (p < .0001). After implantation, 10% of patients who continued to be sexually active experienced no orgasm compared with only 1% before treatment. in addition, more patients experienced late/difficult or weak orgasms (p = .001). CONCLUSION Most men treated with brachytherapy have conserved ejaculatory function after prostate brachytherapy. However, most of these men experience a reduction in volume and a deterioration in orgasm.

Erectile Dysfunction in End-Stage Liver Disease Men

INTRODUCTION In men, erectile dysfunction (ED) is an important issue. Data concerning ED in men with end-stage liver disease (ESLD) is limited, and the risk factors for ED in this population are still unknown. AIMS To determine the prevalence, timescale, and risk factors for ED in ESLD patients candidates to liver transplantation. METHODS Patients candidates for a liver transplantation were asked to participate in a mailed survey about sexual function. Among the 123 eligible men, 98 (84%) agreed to complete the questionnaire. MAIN OUTCOME MEASURES The quality of erection was evaluated using the five-item International Index of Erectile Function (IIEF-5) score, and satisfaction for sexuality, using the patient-baseline Treatment-Satisfaction Scale (TSS) score. Other questions also focused on patient perception of changes over time. RESULTS On the overall population, 28 patients (29%) were nonsexually active. Among the 70 patients who were sexually active, 52 patients (74%) had ED. Regarding the development of ED, 50% of the patients perceived that a deterioration of erectile function occurred within the six previous months. The absence of sexual activity was more frequent in hepatitis B or C patients (P = 0.02). The risk factors for ED were alcohol intake (P = 0.03), tobacco use (P = 0.03), and cardiovascular disease (P = 0.004). The significant risk factors for having a low TSS score were having viral hepatitis (P = 0.01), and cardiovascular disease (P = 0.01). CONCLUSION Population of men with ESLD who are candidates for a liver transplantation is characterized by a high frequency of lack of sexual activity, and by a high prevalence of ED and should be targeted by interventions to improve sexual functioning. These preliminary data need further validation in prospective trial using more comprehensive questionnaires.

Brachytherapy for penile cancer: Efficacy and impact on sexual function

PURPOSE Penis brachytherapy (PB) remains an alternative in the cancer treatment. The objective of this study was to assess the oncologic outcomes, sexual function, and the sexual behavior of men treated by PB for a cancer of the penis. METHODS AND MATERIALS Between 1992 and 2009, 47 patients with a cancer of the penis were treated by PB ((192)Ir), in the Toulouse, Montpellier, and Barcelona cancer centers. The investigation into their sexuality was obtained by means of questionnaire. A total of 21 French patients were approached, of whom 19 (mean age=73.2 years) agreed to answer the questionnaire (participation rate=90.5%). RESULTS Oncologic data: The specific survival and the disease-free survival at 5 years was 87.6% (95% confidence interval, 72.4-94.7%) and 84% (95% confidence interval, 57.6-94.7%), respectively. The rate of preservation of the penis was 66% (n=31). Sexual data: Among the 17 patients sexually active before brachytherapy, 10 patients remained sexually active after treatment (58.8%). Of the 18 patients who had erections before PB, 17 still had them after treatment (94.4%). Age was the main predictive factor. CONCLUSION The PB seems to have a moderated impact on the sexual functions and the sexual behavior of the patients.

Polyorchidism: Presentation of 2 Cases, Review of the Literature and a New Management Strategy

Objectives: To present 2 cases with polyorchidism, to review the literature about polyorchidism, and to propose a rational therapeutic algorithm. Methods: In our institution, we encountered 2 patients with polyorchidism: The 1st patient had bilateral double testis with testicular torsion, and the 2nd patient presented with an indolent scrotal mass. We also performed a literature search (PubMed) for other reports of polyorchidism. Results: Polyorchidism is a rare congenital anomaly that is not well known by most urologists. So far, as illustrated by our 2 cases, the management of polyorchidism is rarely conservative, and usually the supernumerary testis is removed without any evidence supporting this attitude. Rare cases are complicated by torsion (case 1), cryptorchidism, or testicular neoplasm. In case of torsion, the conservative approach depends on the viability of the twisted testis. In case of cryptorchidism, notably in children or young adults, conservative management should be proposed, if technically feasible. In case of signs of malignancy, orchiectomy must be performed. Conclusions: Conservative treatment is advised in all uncomplicated cases. Complicated cases need a careful management, but several situations can be managed conservatively. Based on the literature, we propose a simple, rational therapeutic algorithm.

Ectopic Cushing's syndrome due to a pheochromocytoma: a new case in the post-partum and review of literature.

Cushings syndrome due to AdrenoCorticoTropic Hormone (ACTH)-secreting pheochromocytoma has been rarely reported during pregnancy and post-partum. We report the case of a 30-year-old woman who presented 3 months after delivery acute psychiatric signs and rapid progressive features of Cushings syndrome. Hormonal tests confirmed ACTH-dependant Cushings syndrome. A computed tomography scan revealed a 25×30 mm tumoral mass in the left adrenal gland and octreoscan scintigraphy showed only an uptake of the radiolabelled octreotide by the adrenal tumor. Fractionated 24-h urinary catecholamines and metanephrines were in the normal range, except for slightly increased adrenalin levels. A left laparoscopic adrenalectomy was performed with acute pulmonary oedema following the anesthesia. Histological examination revealed a 3.5×2.5 cm adrenal tumor consistent with a pheochromocytoma without signs of malignancy. The tumor cells immunostained for ACTH and diffuse hyperplasia of adrenocortical cells was observed. After surgery and short stay in intensive care unit, clinical and biological signs rapidly improved and both anti-hypertensive treatment and insulin injections were withdrawn. Genetic testing did not reveal germline mutations in RET protooncogene, Von Hippel Lindau and succinate deshydrogenase genes.

Implication of glutathione in the in vitro antiplasmodial mechanism of action of ellagic acid.

The search for new antimalarial chemotherapy has become increasingly urgent due to parasite resistance to current drugs. Ellagic acid (EA) is a polyphenol, recently found in various plant products, that has effective antimalarial activity in vitro and in vivo without toxicity. To further understand the antimalarial mechanism of action of EA in vitro, we evaluated the effects of EA, ascorbic acid and N-acetyl-L-cysteine (NAC), alone and/or in combination on the production of reactive oxygen species (ROS) during the trophozoite and schizonte stages of the erythrocytic cycle of P. falciparum. The parasitized erythrocytes were pre-labelled with DCFDA (dichlorofluorescein diacetate). We showed that NAC had no effect on ROS production, contrary to ascorbic acid and EA, which considerably reduced ROS production. Surprisingly, EA reduced the production of the ROS with concentrations (6.6×10−9 − 6.6×10−6 M) ten-fold lower than ascorbic acid (113×10−6 M). Additionally, the in vitro drug sensitivity of EA with antioxidants showed that antiplasmodial activity is independent of the ROS production inside parasites, which was confirmed by the additive activity of EA and desferrioxamine. Finally, EA could act by reducing the glutathione content inside the Plasmodium parasite. This was consolidated by the decrease in the antiplasmodial efficacy of EA in the murine model Plasmodium yoelii- high GSH strain, known for its high glutathione content. Given its low toxicity and now known mechanism of action, EA appears as a promising antiplasmodial compound.

The Cumulated Stone Diameter: A Limited Tool for Stone Burden Estimation

OBJECTIVE To compare the performance of the main methods used to estimate stone burden in order to improve and standardize preoperative evaluation of stone disease. METHODS From January 2012 to June 2013, a series of consecutive retrograde intrarenal stone surgery was prospectively evaluated at a single institute. All patients had a pre- and postoperative CT scan. The stone burden was estimated using 3 methods: the cumulative stone diameter (M1), Ackermanns formula (M2), and the sphere formula (M3). The predictive value of the postoperative stone-free status of these methods was then compared. RESULTS Overall (n = 142), the stone-free rate was 64%. The three methods (M1, M2, and M3) were all predictive of stone-free status for stones <20 mm (P = .0076, .018, and .016, respectively). However, only M2 and M3 were significant for stones >20 mm (P = .0024 and .023). Using receiver operating characteristic curves, we found that areas under the curve were 0.73, 0.70, and 0.71 for stones below 20 mm and 0.53, 0.74, and 0.74 for stones above 20 mm for M1, M2, and M3, respectively. In multivariate analysis, M1 and M3 were both found to be independently associated with the stone-free status in the whole series (P <.001 and .011, respectively). However, for stones above 20 mm, only M3 was significant (P = .020). CONCLUSION Evaluation of the stone burden is an important predictor of the outcome of retrograde intrarenal stone surgery. For stones below 20 mm, all the three methods approximate stone burden correctly; however, for the stones above 20 mm, calculation of volume is recommended.