Young urologists and kidney transplantation training: A survey designed by the French Transplantation Committee of the French Association of Urology (CTAFU) and the French Association of Urologists in training (AFUF).

OBJECTIVE: In France, kidney transplantations (KT) are mainly performed by urologist. Young urologists and residents are involved in this activity mostly performed in emergency. How do they feel about KT training? Is KT an attractive part of the urologist activity? METHODS: This survey has been designed in the form of a questionnaire by the French Committee of Kidney Transplantation (CTAFU) and the French Association of Urologists in training (AFUF). It has been sent by e-mail to all the AFUF members. Interest in KT and performance of the training were evaluated. RESULTS: In total, 126 members filed the form. Among the residents, 51.5% feel secure to perform KT at the end of their residency. KT is considered as an interesting surgery for 92.1% of the participants: 76.5% are willing to get involved in KT during their residency/fellowship. Among the participants, 44% are willing to continue a long-term involvement. Among the residents, 65.9% consider their practical training insufficient: 56.8% have been supervised for a KT performance during their residency and 86% declare a lack of practical training and had a patient-based learning. Among the residents, 92.1% declare an insufficient theorical training. Among the residents, 33.3% say the schedules of transplantation limit their interest in KT. Among the participants, 34.4% receive a transplant bonus in addition to the usual on-call salary. CONCLUSION: Young urologists wish to continue their involvement in KT activity, but improved theoretical and practical training are essential. In addition, the conditions under which this activity is performed and remunerated are a matter of concern.

Expression of LHCGR in Pheochromocytomas Unveils an Endocrine Mechanism Connecting Pregnancy and Epinephrine Overproduction.

BACKGROUND: The mechanisms by which pregnancy may unmask pheochromocytomas and paragangliomas are not totally understood. We hypothesized that gestational hormones may participate in the pathophysiology of catecholamine excess during pregnancy. We report a case of silent pheochromocytoma revealed in a pregnant woman by life-threatening adrenergic myocarditis. METHODS: In vitro studies were conducted to investigate the effect of estradiol and the pregnancy hormone hCG (human chorionic gonadotropin) on epinephrine secretion by cultured cells derived from the patient's tumor. Expression of LHCG (luteinizing hormone/chorionic gonadotropin) receptor was searched for in the patient's tumor, and a series of 12 additional pheochromocytomas by real-time reverse transcription polymerase chain reaction and immunohistochemistry. LHCGR expression was also analyzed in silico in the pheochromocytomas and paragangliomas cohorts of the Cortico et Médullosurrénale: les Tumeurs Endocrines and The Cancer Genome Atlas databases. RESULTS: hCG stimulated epinephrine secretion by cultured cells derived from the patient's pheochromocytoma. The patient's tumor expressed the LHCG receptor, which was colocalized with catecholamine-producing enzymes. A similar expression pattern of the LHCG receptor was also observed in 5 out of our series of pheochromocytomas. Moreover, in silico studies revealed that pheochromocytomas and paragangliomas display the highest expression levels of LHCG receptor mRNA among the 32 solid tumor types of The Cancer Genome Atlas cohort. CONCLUSIONS: Pregnancy may thus favor surges in plasma catecholamine and hypertensive crises through hCG-induced stimulation of epinephrine production by pheochromocytomas.

The neuropeptide substance P regulates aldosterone secretion in human adrenals.

Aldosterone, produced by the adrenals and under the control of plasma angiotensin and potassium levels, regulates hydromineral homeostasis and blood pressure. Here we report that the neuropeptide substance P (SP) released by intraadrenal nerve fibres, stimulates aldosterone secretion via binding to neurokinin type 1 receptors (NK1R) expressed by aldosterone-producing adrenocortical cells. The action of SP is mediated by the extracellular signal-regulated kinase pathway and involves upregulation of steroidogenic enzymes. We also conducted a prospective proof-of-concept, double blind, placebo-controlled clinical trial aimed to investigate the impact of the NK1R antagonist aprepitant on aldosterone secretion in healthy male volunteers (EudraCT: 2008-003367-40, ClinicalTrial.gov: NCT00977223). Participants received during two 7-day treatment periods aprepitant (125 mg on the 1st day and 80 mg during the following days) or placebo in a random order at a 2-week interval. The primary endpoint was plasma aldosterone levels during posture test. Secondary endpoints included basal aldosterone alterations, plasma aldosterone variation during metoclopramide and hypoglycaemia tests, and basal and stimulated alterations of renin, cortisol and ACTH during the three different stimulatory tests. The safety of the treatment was assessed on the basis of serum transaminase measurements on days 4 and 7. All pre-specified endpoints were achieved. Aprepitant decreases aldosterone production by around 30% but does not influence the aldosterone response to upright posture. These results indicate that the autonomic nervous system exerts a direct stimulatory tone on mineralocorticoid synthesis through SP, and thus plays a role in the maintenance of hydromineral homeostasis. This regulatory mechanism may be involved in aldosterone excess syndromes.

Surgical Outcomes of Urinary Tract Deep Infiltrating Endometriosis.

OBJECTIVE: To report the outcomes of surgical management of urinary tract endometriosis. DESIGN: Retrospective study based on prospectively recorded data (NCT02294825) (Canadian Task Force classification II-3). SETTING: University tertiary referral center. PATIENTS: Eighty-one women treated for urinary tract endometriosis between July 2009 and December 2015 were included, including 39 with bladder endometriosis, 31 with ureteral endometriosis, and 11 with both ureteral and bladder endometriosis. Owing to bilateral ureteral localization in 8 women, 50 different ureteral procedures were recorded. INTERVENTION: Procedures performed included resection of bladder endometriosis nodules, advanced ureterolysis, ureteral resection followed by end-to-end anastomosis, and ureteroneocystostomy. MEASUREMENTS AND MAIN RESULTS: The main outcome measure was the outcome of the surgical management of urinary tract endometriosis. Fifty women presented with deep infiltrating endometriosis (DIE) of the bladder and underwent either full-thickness excision of the nodule (70%) or excision of the bladder wall without opening of the bladder (30%). Ureteral lesions were treated by ureterolysis in 78% of the patients and by primary segmental resection in 22%. No patient required nephrectomy. Histological analysis revealed intrinsic ureteral endometriosis in 54.5% of cases. Clavien-Dindo grade III complications were present in 16% of the patients who underwent surgery for ureteral nodules and in 8% of those who underwent surgery for bladder endometriosis. Overall delayed postoperative outcomes were favorable regarding urinary symptoms and fertility. Patients were followed up for a minimum of 12 months and a maximum of 7 years postoperatively, with no recorded recurrences. CONCLUSION: Surgical outcomes of urinary tract endometriosis are generally satisfactory; however, the risk of postoperative complications should be taken into consideration. Therefore, all such procedures should be managed by an experienced multidisciplinary team.

Diagnostic performance of contrast-enhanced ultrasonography and magnetic resonance imaging for the assessment of complex renal cysts: A prospective study.

OBJECTIVES: To compare the diagnostic performance of computed tomography, magnetic resonance imaging and contrast enhanced ultrasonography for the assessment of complex renal cysts. METHODS: We carried out a prospective single-center study from January 2012 to December 2013. We included patients with Bosniak category 2F or 3 renal cysts found on computed tomography and reviewed by two expert radiologists. Magnetic resonance imaging and contrast-enhanced ultrasonography were then carried out. Patients with a Bosniak ≥3 cyst on magnetic resonance imaging, as well as those upgraded as appearing malignant on contrast-enhanced ultrasonography, were surgically managed. Imaging results were compared with histological data. For patients without surgery, imaging examinations were compared with follow-up data. For each imaging examination, diagnostic performance and Cohen's kappa coefficient were assessed. RESULTS: A total of 47 patients were included. The median follow up was 36 months (range 17-48 months). At initial computed tomography, cysts were classified as Bosniak 2F and Bosniak ≥3 in 34 and 13 patients, respectively. Magnetic resonance imaging found 13 Bosniak ≥3 cysts, and contrast-enhanced ultrasonography upgraded six more patients with cysts that appeared malignant. A total of 19 patients had surgery. Histological analysis reported 14 malignant tumors. No tumor progression was found in followed-up patients. Computed tomography showed poor sensitivity (36%) and specificity (76%; κ = 0.11). Magnetic resonance imaging showed 71% sensitivity and 91% specificity (κ = 0.64). Contrast-enhanced ultrasonography showed high sensitivity (100%) and specificity (97%), and a negative predictive value at 100% (κ = 0.95). CONCLUSIONS: The present results suggested that contrast-enhanced ultrasonography could be useful in improving the assessment of complex renal cysts. Indeed, computed tomography accuracy might be limited in this indication requiring further investigations to determine the best treatment strategy.

Baseline chronic kidney disease is associated with toxicity and survival in patients treated with targeted therapies for metastatic renal cell carcinoma.

To assess the impact of baseline chronic kidney disease on targeted therapy (TT)-induced toxicities and survival in patients treated for metastatic renal cell carcinoma (mRCC). Data from patients receiving first-line TT from January 2006 to June 2012 were collected retrospectively. TT side effects, time to treatment failure (TTF), and overall survival (OS) were analyzed according to the baseline glomerular filtration rate (GFR) calculated using the modification diet in renal disease formula. Hundred and two patients treated with sunitinib (N=67), sorafenib (N=24), or temsirolimus (N=11) were included. Forty-two patients (41%) had baseline chronic kidney disease with GFR less than 60 ml/min/1.73 m. Patients with GFR less than 60 were more likely to encounter severe (grade 3-4) TT-induced toxicities (79 vs. 32%, P<0.0001). Moreover, renal function impairment was significantly associated with higher median TTF and OS (respectively, 12 vs. 6 months for TTF, P=0.003; and 33 vs. 13 months for OS, P=0.001). On multivariate analysis, GFR less than 60 was identified as the only factor associated with a higher rate of severe toxicity: odds ratio=4.74 (1.67-13.41), P=0.003. Severe toxicity (P=0.05) was identified as an independent prognostic factor for OS and TTF. Baseline chronic kidney disease was associated with higher TT-induced toxicities, which were identified as a prognostic factor of higher survival in mRCC treatment. These results suggest that GFR measurement could be used to optimize the efficacy of TT in patients treated for an mRCC.

Positive surgical margins and their locations in specimens are adverse prognosis features after radical cystectomy in non-metastatic carcinoma invading bladder muscle: results from a nationwide case-control study.

OBJECTIVE: To compare the prognoses associated with positive surgical margins (PSMs) according to their urethral, ureteric and/or soft tissue locations in patients with pN0 M0 bladder cancer who have not undergone neoadjuvant chemotherapy. PATIENTS AND METHODS: A retrospective, case-control study was conducted between 1991 and 2011 using data from 17 academic centres in France. A total of 154 patients (cases) with PSMs met the eligibility criteria and were matched according to centre, pT stage, gender, age and urinary diversion method with a population-based sample of 154 patients (controls) from 3651 patients who had undergone cystectomies. The median follow-up period was 23.9 months. Multivariable Cox regression analysis was used to test the effects of PSMs on local recurrence (LR)-free survival, metastatic recurrence (MR)-free survival and cancer-specific survival (CSS). RESULTS: The 5-year LR-free survival and CSS rates of patients with urethral and soft tissue PSMs were lower than those in the control group. A significant decrease in CSS was associated with soft tissue PSMs (P = 0.003, odds ratio = 0.425, 95% confidence interval 0.283-0.647). The prognosis was not affected in cases of ureteric PSMs. CONCLUSIONS: Soft tissue PSMs were associated with poor CSS rates in patients with pN0 M0 bladder cancer. A correlation between urethrectomy and a reduction of the risk of LR in a urethral PSM setting was observed.