Activation of Prejunctional P2x2/3 Heterotrimers by ATP Enhances the Cholinergic Tone in Obstructed Human Urinary Bladders.

The objective of this study was to investigate the role of ATP in cholinergic neurotransmission in the urinary bladder of control men and of patients obstructed as a result of benign prostatic hyperplasia (BPH). Human detrusor samples were collected from 41 patients who submitted to transvesical prostatectomy resulting from BPH and 26 male organ donors. The release of [3H]acetylcholine ([3H]ACh) was evoked by electrical field stimulation (10 Hz, 200 pulses) in urothelium-denuded detrusor strips. Myographic recordings were performed to test detrusor strip sensitivity to ACh and ATP. Nerve-evoked [3H]ACh release was 1.5-fold higher in detrusor strips from BPH patients compared with controls. This difference was abolished after desensitization of ionotropic P2X1-3 receptors with an ATP analog, α,ß-methylene ATP (30 µM, applied for 15 minutes). TNP-ATP (10 nM, a preferential P2X2/3 antagonist) and A317491 (100 nM, a selective P2X3 antagonist) were about equipotent in decreasing nerve-evoked [3H]ACh release in control detrusor strips, but the selective P2X1 receptor antagonist NF023 (3 µM) was devoid of effect. The inhibitory effect of TNP-ATP (10 nM) increased from 27% ± 9% to 43% ± 6% in detrusor strips of BPH patients, but the effect of A317491 (100 nM) [3H]ACh release unaltered (20% ± 2% vs. 24% ± 4%). The amplitude of ACh (0.1-100 µM)-induced myographic recordings decreased, whereas sensitivity to ATP (0.01-3 mM) increased in detrusor strips from BPH patients. Besides the well characterized P2X1 receptor-mediated contractile activity of ATP in pathologic human bladders, we show here for the first time that cholinergic hyperactivity in the detrusor of BPH patients is facilitated by activation of ATP-sensitive P2X2/3 heterotrimers. SIGNIFICANCE STATEMENT: Bladder outlet obstruction often leads to detrusor overactivity and reduced bladder compliance in parallel to atropine-resistant increased purinergic tone. Our data show that P2X1 purinoceptors are overexpressed in the detrusor of patients with benign prostatic hyperplasia. Besides the P2X1 receptor-mediated detrusor contractions, ATP favors nerve-evoked acetylcholine release via the activation of prejunctional P2X2/3 excitatory receptors in these patients Thus, our hypothesis is that manipulation of the purinergic tone may be therapeutically useful to counteract cholinergic overstimulation in obstructed patients.

Which One Is the Best for Living Donation: A Multiple-Artery Left Kidney Nephrectomy or a Right Kidney Nephrectomy?

INTRODUCTION: The current approach in living-donor kidney transplant is to preserve the best kidney for the donor and harvest the contralateral one. Due to a shorter renal vein and a greater incidence of venous thrombosis, left kidneys are more frequently elected. Notwithstanding, arterial anatomy may be complex and thus render the transplantation procedure more difficult and prone to complications. OBJECTIVES: To analyze the outcomes after multiple-artery left kidney nephrectomy (MALKN) and right kidney nephrectomy (RKN). RESULTS: Seventy-three cases were performed from 1999 to 2017 in our institution: 34 MALKN and 39 RKN. The mean operative time was significantly longer in MALKN. Warm ischemia time, donor and receptor hospital stay, and postoperative complications did not differ between groups. There was a positive correlation between renal arteries' ostia distance in MALKN and the duration of warm ischemia period. There was no significant difference in the incidence of acute tubular necrosis, first-year variations in serum creatinine, and glomerular filtration rate between groups. Long-term graft survival did not significantly differ between groups. Three cases of vein thrombosis after RKN were reported with graft loss. CONCLUSION: The safety and efficacy of MALKN does not differ from RKN, although there appears to be a higher incidence of vein thrombosis after right kidney transplantation. Despite being technically more demanding, particularly in cases with distant artery ostia, MALKN could be a better option than RKN for living donation, expanding the available donor pool, although more studies are needed to affirm this conclusion.

Ureteral Stenosis After Renal Transplantation-A Single-Center 10-Year Experience.

BACKGROUND: Kidney transplantation (KT) is the definitive treatment for ESRD. Ureteral stenosis (US) is one of the most common urologic complications and has been reported in 2.6%-15% of KTs. METHODS: We reviewed data for 973 consecutive KT procedures performed at our center from January 2004 to September 2014, with evaluation of US management and recurrence rate. RESULTS: The 973 KTs were performed with the use of the direct ureterovesical (UV) implantation Paquin technique, and the mean follow-up time was 44.3 ± 30.2 [range, 3-111] months. During this period, 33 cases of US (3.39%) were reported. The interval from KT to US diagnosis was 10.6 ± 23.0 (range, 0.5-98.0) months. The majority of the US cases were located in the distal ureter and UV junction (83.9%), with only 2 cases of middle ureter stenosis and 2 cases of ureteropelvic junction. Mean US length was 2.5 ± 1.9 (range, 1.0-10.0) cm. Surgical management and global and treatment-specific recurrence rates were reviewed. Primary surgical treatment recurrence rate was higher for the endoscopic approach, with a mean global time from treatment to US recurrence of 6.9 ± 16.3 (range, 0-65) months and a median of 2.0 months. Open surgical approach was the main recurrence treatment option (74%). There were 2 cases of graft loss. Success rate evaluation of overall and treatment-specific primary surgical management did not reveal significant differences (P > .05) according to stenosis length (<1.5, 1.5-3.0, or >3.0 cm), time between transplant and stenosis (≤3, 3-12, or >12 mo), or stenosis location (distal, middle, or upper ureter). However, there was clearly a trend to higher success rate in smaller stenosis (<1.5 cm) and early management (≤3 mo), particularly with the use of balloon dilation. CONCLUSIONS: US management should be decided on a case-by-case basis according to clinical characteristics, treatment-specific recurrence rate, and previous surgical options.

Impairment of ATP hydrolysis decreases adenosine A1 receptor tonus favoring cholinergic nerve hyperactivity in the obstructed human urinary bladder.

This study was designed to investigate whether reduced adenosine formation linked to deficits in extracellular ATP hydrolysis by NTPDases contributes to detrusor neuromodulatory changes associated with bladder outlet obstruction in men with benign prostatic hyperplasia (BPH). The kinetics of ATP catabolism and adenosine formation as well as the role of P1 receptor agonists on muscle tension and nerve-evoked [(3)H]ACh release were evaluated in mucosal-denuded detrusor strips from BPH patients (n = 31) and control organ donors (n = 23). The neurogenic release of ATP and [(3)H]ACh was higher (P < 0.05) in detrusor strips from BPH patients. The extracellular hydrolysis of ATP and, subsequent, adenosine formation was slower (t (1/2) 73 vs. 36 min, P < 0.05) in BPH detrusor strips. The A(1) receptor-mediated inhibition of evoked [(3)H]ACh release by adenosine (100 µM), NECA (1 µM), and R-PIA (0.3 µM) was enhanced in BPH bladders. Relaxation of detrusor contractions induced by acetylcholine required 30-fold higher concentrations of adenosine. Despite VAChT-positive cholinergic nerves exhibiting higher A(1) immunoreactivity in BPH bladders, the endogenous adenosine tonus revealed by adenosine deaminase is missing. Restoration of A1 inhibition was achieved by favoring (1) ATP hydrolysis with apyrase (2 U mL(-1)) or (2) extracellular adenosine accumulation with dipyridamole or EHNA, as these drugs inhibit adenosine uptake and deamination, respectively. In conclusion, reduced ATP hydrolysis leads to deficient adenosine formation and A(1) receptor-mediated inhibition of cholinergic nerve activity in the obstructed human bladder. Thus, we propose that pharmacological manipulation of endogenous adenosine levels and/or A(1) receptor activation might be useful to control bladder overactivity in BPH patients.

From Open to Laparoscopic Living-donor Nephrectomy: Changing the Paradigm in a High-volume Transplant Center.

In 1995, Ratner et al reported the first laparoscopic living-donor nephrectomy, and since then this approach is gradually replacing traditional open surgery. The learning curve of the procedure is still unclear and lessons taken from initial experience series are of utmost importance. We retrospectively analyzed our initial 50 living-donor laparoscopic nephrectomies, of which 90% were performed on the left side. Renal vascular variation occurred in 28% of donors. The median age and body mass index of the donors were 50 years (IQR 39-55) and 24.65 kg/m(2) (IQR 22.5-27.3), respectively. The median operative time and warm ischemia time were 160 minutes (IQR 141-178) and 240 seconds (IQR 210-280), respectively. Estimated blood loss was 60 mL (IQR 60-127.5). The serum creatinine of the receptors was 97.6 µmol/L (IQR 87.5-139.6) 1 month after transplant. Overall, there were 5 complications, including 2 (4%) open conversions, 1 (2%) incisional hernia, 1 (2%) graft loss, and 1 (2%) reintervention. The body mass index and the multiple arteries did not influence the operative time and warm ischemia time or the recipient's serum creatinine level. Along the series, there was a significant reduction in the operative time (Spearman ρ = -5.2; P < .001), but no significant differences were found for warm ischemia time, blood loss, or serum creatinine of the recipients (P > .05). Laparoscopic donor nephrectomy is a safe procedure in centers experienced in laparoscopic surgery; however, the learning curve plateau was not reached after the initial 50 cases.

Female sexual function and depression after kidney transplantation: comparison between deceased- and living-donor recipients.

Disturbances in sexual function and depression are a common feature in women with chronic renal failure. Living-donor kidney transplantation seems to warrant better results than its cadaveric counterpart in many aspects but its impact on post-transplantation sexual function remains unknown. This study aimed to compare post-transplantation sexual function and depression in women receiving kidney grafts from living and deceased donors. From a single-center prospective database of 2016 renal transplantations between June 2011 and June 2013, we enrolled 50 sexually active women after kidney transplantation. Female sexual function was evaluated with the Female Sexual Function Index Questionnaire (FSFI) and depression was assessed using the Beck Depression Inventory-II (BDI-II) scale. Thirty-four patients referred the questionnaires. The sexual domains of satisfaction and desire were significantly better in living-donor receptors; in all other domains evaluated by FSFI no statistically significant difference was encountered between groups, although living-donor receptors tended to report better function. Total BDI-II was well correlated with total FSFI score in our study cohort (Spearman's rho = -0.80, P < .001). Only 34.6% of women referred to have discussed sexual issues with their physicians before transplantation, whereas 73.1% stated it would have been important. In conclusion, living-donor transplantation exerted a positive effect on women's sexual function.

Allograft nephrectomy: a single-institution, 10-year experience.

INTRODUCTION: Allograft nephrectomy (AN) is associated with a high number of surgical complications. Some authors advocate that early nephrectomy (<1 year) is associated with fewer complications. Intracapsular (ICAN) and extracapsular AN (ECAN) might have a different impact on allosensitization and surgical outcomes. Our goal was to compare surgical outcomes between early and late AN in our institution and to compare ICAN and ECAN in terms of surgical outcomes and panel reactive antibodies (PRA) variation. MATERIALS AND METHODS: Between January 2000 and October 2012, we performed 104 AN at our institution (32 early and 72 late). Comparisons between early and late AN, and, within the latter, between the 2 different techniques were sought. Statistical analysis was performed for sample description, group comparison and %PRA variation. RESULTS: Among the 104 patients with a mean age of 47.9 ± 14.2 years, 54 were men. Age, gender, body mass index, and number of previous transplants were similar between early and late AN and between ICAN and ECAN patients. Late AN was associated with less blood loss (293.4 ± 229.0 vs 414.3 ± 349.5 mL; P = .03), shorter hospital stay (12.8 ± 14.5 vs 26.8 ± 26.5; P < .05), and fewer complications (22.2% vs 59.3%; P < .05). The chance of being relisted for transplantation was similar (50.0% in early vs 59.7% in late AN; P = .7). When comparing ICAN and ECAN, there was no difference in surgical outcomes. The %PRA variation between the 2 techniques was comparable (-1.2 ± 10.6 ICAN vs -0.5 ± 15.9 ECAN; P = .8), as was the chance of being relisted for transplantation (60.5% ICAN vs 58.6% ECAN; P = .8). CONCLUSIONS: Early AN was associated with a greater number of surgical complications. Nevertheless, the number of AN patients returning to the active waiting list was similar between early and late AN groups. ICAN and ECAN had similar surgical and postoperative outcomes, although a bias may be present because some conversions from ECAN to ICAN occurred owing to technical issues. As in other studies, ICAN did not seem to affect allosensitization or jeopardize the chance of being relisted for transplant when compared with ECAN.

Living versus cadaveric-donor renal transplant recipients: a comparison on sexual function.

Erectile dysfunction is experienced by 50% of men with end-stage renal disease (ESRD) and uremia. The origin of this dysfunction is multifactorial. The aim of this study was to compare living donor versus cadaveric donor transplant recipients regarding male sexual function. Seventy-seven sexually active male kidney transplant recipients (44 from living donors; 33 from cadaveric donors) were randomly selected from our single-center prospective database of 2016 renal transplants. Epidemiological and clinical data were collected between June 2010 and June 2011. Male sexual function was evaluated with the International Index of Erectile Function questionnaire (IIEF-15). We assessed the prevalence of male sexual dysfunction according to established cutoff points for each of the IIEF-15 domains. Mann-Whitney and Pearson's chi- square statistical tests were used to compare continuous and categorical variables, respectively. The median age at the time of completion of the questionnaires was 43 and 51 years (P = .003) with median times from transplantation was of 36 and 42 months for living donor and cadaveric donor recipients, respectively (P = .31). Median durations of ESRD before surgery were 17.5 and 57 months for living donor and cadaveric donor recipients, respectively (P < .001). Living donor and cadaveric donor recipients had median creatinine clearance values of 55 and 57 mL/min, respectively (P = .44). Median time after renal transplantation for first sexual intercourse was 1 and 2 months for living donor and cadaveric donor recipients, respectively (P = .35). Median body mass indices for living donor and cadaveric donor recipients were 24.8 and 24, respectively (P = .31). Regarding sexual function domains, there were significant differences only for intercourse satisfaction. In our cohort, living donor recipients tended to be younger, have shorter time of ESRD, and less incidence of hypertension or diabetes mellitus but with greater tobacco use. In conclusion, living donor transplantation exerted a favorable impact on sexual function.

Comparative study of gene expression in patients with varicocele by microarray technology.

The aim of the present study was to evaluate gene expression profile by microarray technology and validation by real-time PCR in paired samples of testicular biopsies (pre-surgery and post-surgery) in two patients with varicocele. The microarray analysis showed increased expression levels after surgery in 215 and 52 genes in patient 1 and 2, respectively, as well as decreased expression levels in 65 genes in patient 1 and 358 genes in patient 2. Real-time PCR confirmed the differential expression of the five selected genes: MT1M, PHLDA1 and INSL3 had decreased expression levels and CCIN and PRM2 increased expression levels compared with pre-surgery biopsies. In conclusion, both techniques showed decreased expression levels of genes involved in stress situations associated with varicocele and increased expression levels of genes involved in normal function of spermatogenesis.

[Multiple schwannoma of the penis]. / Schwanoma mútiple del pene.

Schwannoma or neurilemmoma designate a tumour that originates in the Schwann cells of peripheral nerves, therefore occurring anywhere in the body. They are very rare in the penis. In the literature are reported twenty seven cases of penile schwannoma. We report a case of multiple schwannoma of the penis and make a brief literature revision about this rare pathology.

Schwanoma múltiple del pene / Multiple schwannoma of the pennis

El schwanoma o neurilemoma es un tumor con origen en las células de Schwann de la vaina de los nervios periféricos. En la literatura están descritos veintisiete casos de schwanomas del pene. Presentamos un caso de schwanoma múltiple del pene, haciendo una breve revisión de la literatura sobre este raro tumor con respecto a su etiopatogenia, diagnóstico, tratamiento y orientación

Schwannoma or neurilemmoma designate a tumour that originates in the Schwann cells of peripheral nerves, therefore occurring anywhere in the body. They are very rare in the penis. In the literature are reported twenty seven cases of penile schwannoma. We report a case of multiple schwannoma of the penis and make a brief literature revision about this rare pathology

The CAG repeat within the androgen receptor gene and its relationship to cryptorchidism.

PURPOSE: We examined the significance of the CAG repeat polymorphism in the pathogenesis of cryptorchidism. MATERIALS AND METHODS: Genomic deoxyribonucleic acid (DNA) was extracted from blood samples from 42 cryptorchid boys and from 31 non-cryptorchid control subjects. In the cryptorchid group, 7 had bilateral cryptorchidism and 6 had patent processus vaginalis in the contralateral side. To determine the number of CAG repeats, the DNA was amplified by polymerase chain reaction and sequenced. RESULTS: The mean CAG repeat length in the AR gene was 22.5 (range 16 to 28) in patients and 21.5 (range 17 to 26) in controls (non-significant). Patients with bilateral cryptorchidism had a mean length of 24.3 (range 21 to 26) and patients with unilateral cryptorchidism and patent processus vaginalis in the contra lateral side had a mean of 25.2 (range 21 to 28), which was statistically different from controls (p = 0.015 and p = 0.005 respectively). CONCLUSION: CAG repeat length of the AR gene does not seem to play a major role in patients with unilateral cryptorchidism. However, in patients with bilateral undescended testis, a less functional androgen receptor through a longer polyglutamine chain may have a role in its pathogenesis. In the same way, patients with unilateral cryptorchidism a contralateral patent processus vaginalis have longer CAG repeats that might be responsible for a slower testicular descent and incomplete closure of the processus vaginalis.

The CAG repeat within the androgen receptor gene and its relationship to cryptorchidism

PURPOSE: We examined the significance of the CAG repeat polymorphism in the pathogenesis of cryptorchidism. MATERIALS AND METHODS: Genomic deoxyribonucleic acid (DNA) was extracted from blood samples from 42 cryptorchid boys and from 31 non-cryptorchid control subjects. In the cryptorchid group, 7 had bilateral cryptorchidism and 6 had patent processus vaginalis in the contralateral side. To determine the number of CAG repeats, the DNA was amplified by polymerase chain reaction and sequenced. RESULTS: The mean CAG repeat length in the AR gene was 22.5 (range 16 to 28) in patients and 21.5 (range 17 to 26) in controls (non-significant). Patients with bilateral cryptorchidism had a mean length of 24.3 (range 21 to 26) and patients with unilateral cryptorchidism and patent processus vaginalis in the contra lateral side had a mean of 25.2 (range 21 to 28), which was statistically different from controls (p = 0.015 and p = 0.005 respectively). CONCLUSION: CAG repeat length of the AR gene does not seem to play a major role in patients with unilateral cryptorchidism. However, in patients with bilateral undescended testis, a less functional androgen receptor through a longer polyglutamine chain may have a role in its pathogenesis. In the same way, patients with unilateral cryptorchidism a contralateral patent processus vaginalis have longer CAG repeats that might be responsible for a slower testicular descent and incomplete closure of the processus vaginalis.

[Leiomyoma of the bladder. Analysis of a collection of 90 cases]. / Leiomioma de vejiga. Análisis de agregación de 90 casos.

INTRODUCTION: Bladder leiomyomas (BL) are rare. Most publications regarding these tumours are reports of isolated cases; therefore they don't allow an evaluation of diagnostic and treatment procedures. MATERIAL & METHODS: We preformed a pooled analysis of 90 cases of BL reported in the literature. RESULTS: Mean age was 45.3 (19 to 85 years), 68 (75.6%) were women. Filling symptoms were the most frequently reported (50%), followed by voiding symptoms (24.4%). Twenty four patients (26.7%) were asymptomatic. Tumours were endoluminal in 46 patients (51.1%), intramural in 27 (30%) and extravesical in 15 (16.7%). A laparotomy was performed in 56 patients (62.2%), with enucleation in 29 (32.2%), partial cystectomy in 25 (27.8%) and total cystectomy in 2 (2.2%). A transurethral resection was preformed in 27 (30%) and a transvaginal resection in 5 (5.6%). Two patients underwent conservative treatment. In 3 cases there were reports of recurrence and one patient got a vesicovaginal fistula. CONCLUSIONS: Although BL are rare, when evaluating bladder tumours, imaging techniques can make suspect of this neoplasm. Surgical treatment of these tumours has a very high success rate. Usually an enucleation or a transurethral resection is sufficient to render the patient tumour free, avoiding a more iatrogenic surgery.

Leiomioma de vejiga. Análisis de agregación de 90 casos / Bladder leiomyoma. A pooled analysis of 90 cases

INTRODUCCIÓN: Los leiomiomas de vejiga (LV) son tumores raros. La mayoría de las publicaciones relativas a estos tumores describen casos aislados, no permitiendo evaluar estrategias diagnósticas y terapéuticas. MATERIAL Y MÉTODO: Realizamos un análisis de agregación de 90 casos de LV descritos en la literatura internacional. RESULTADOS: La edad media al diagnóstico fue de 45,3 años (19-85 años), 68 (75,6 por ciento) eran mujeres. Los síntomas más frecuentes eran de almacenamiento (50 por ciento) seguidos de los de vaciado (24,4 por ciento). Veinticuatro pacientes (26,7 por ciento) estaban asintomáticos. Cuarenta y seis tumores (51,1 por ciento) tenían crecimiento endoluminal, 27 (30 por ciento) eran intramurales y 15 (16,7 por ciento) extravesicales. A 56 pacientes (62,2 por ciento) se les realizó una laparotomía, con enucleación en 29 (32,2 por ciento), cistectomía parcial en 25 (27,8 por ciento) y cistectomía total en 2 (2,2 por ciento). Veintisiete (30 por ciento) fueron sometidos a resección transuretral y 5 pacientes (5,6 por ciento) a una enucleación transvaginal. Dos pacientes no fueron sometidos a ningún tratamiento. Fueron descritas 3 recidivas y una fístula vesicovaginal como única complicación. CONCLUSIONES: Aunque el LV sea un tumor raro, en el estudio de una neoformación vesical, los estudios de imagen, pueden hacer sospechar este diagnóstico. El tratamiento quirúrgico tiene una alta tasa de éxito. En la mayoría de los casos, la resección transuretral o la enucleación es suficiente, evitando así una cirugía más iatrogénica (AU)