Association between Smoking Exposure, Neoadjuvant Chemotherapy Response and Survival Outcomes following Radical Cystectomy: Systematic Review and Meta-Analysis.

PURPOSE: Studies exploring the association of cigarette smoking and long-term survival outcomes following radical cystectomy have yielded mixed results. We performed a systematic review and meta-analysis to investigate the impact of tobacco smoking exposure, duration, intensity and cessation on response to neoadjuvant chemotherapy and long-term survival outcomes in patients undergoing radical cystectomy for bladder cancer. MATERIALS AND METHODS: We systematically searched PubMed®, MEDLINE®, Embase® and Cochrane® Library databases for original articles published before April 2019. Primary end points were neoadjuvant chemotherapy response, overall and cancer specific mortality, and recurrence-free survival after radical cystectomy. Observational studies reporting Cox proportional hazards regression or logistic regression analysis were independently screened. Available multivariable hazard ratios and corresponding 95% CIs were included in the quantitative analysis. Sensitivity analyses were performed as appropriate. A risk of bias assessment was completed for nonrandomized studies. RESULTS: Our electronic search identified a total of 649 articles. After a detailed review we selected 17 studies that addressed the impact of smoking status on survival outcomes in 13,777 patients after radical cystectomy for bladder cancer. Pooled meta-analysis revealed that active smokers have an increased risk of overall mortality (HR 1.21, 95% CI 1.08-1.36; p=0.001, I2=0%), cancer specific mortality (HR 1.24, 95% CI 1.13-1.36; p <0.00001, I2=0%) and bladder cancer recurrence (HR 1.24, 95% CI 1.12-1.38; p <0.0001, I2=3%). Sensitivity analyses evaluating only patients who underwent neoadjuvant chemotherapy followed by radical cystectomy showed an advantage of non/never smokers in terms of neoadjuvant chemotherapy complete response rate (HR 0.47, 95% CI 0.29-0.75; p=0.001, I2=0%). CONCLUSIONS: Smoking status is associated with lower neoadjuvant chemotherapy response rates and higher overall and cancer specific mortality as well as bladder cancer recurrence after radical cystectomy. Appropriate preoperative counseling, together with tightened followup, may have a pivotal role in improving the smoking-related long-term survival outcomes in patients with bladder cancer.

Idiopathic stuttering priapism treated with salbutamol orally: a case report.

Recurrent ischaemic priapism also known as stuttering priapism is an uncommon form of ischaemic priapism, and its treatment is not yet clearly defined. If left untreated, it may evolve into classic form of acute ischaemic priapism and lead to erectile dysfunction due to fibrosis of corpora cavernosa. Several drugs have been proposed with variable results and only supported with level three or four of evidence. Hormonal therapy such as cyproterone acetate, oestrogen, bicalutamide or Lh-Rh agonist are often effective but can cause side effects such as hypogonadal state and infertility. Other medical options are 5-alpha-reductase and phosphodiesterase-5 inhibitors, ketoconazole, baclofen, digoxin, gabapentin and beta-2-agonist terbutaline. We report the first case of stuttering priapism treated with beta-2-agonist salbutamol.

A unique case of late complication of rectum mesh erosion after laparoscopic sacrocolpopexy.

Sacrocolpopexy, a surgical technique with a low morbidity rate, is a valid procedure for repairing vaginal vault prolapse. To our knowledge, only 1 case of rectum erosion after open sacrocolpopexy has been reported in the literature, and there is no record of any such incident after laparoscopic sacrocolpopexy. We report the first case of mesh erosion involving the rectum instead of the vagina assessed 8 years after laparoscopic sacrocolpopexy.

Human papillomavirus infection and vaginal tape exposure after midurethral sling: a case report.

Midurethral tape placement is the gold standard procedure for stress urinary incontinence (SUI). Among reported complications, tape erosion is uncommon. Several risk factors have been postulated as causes of vaginal erosion, but none have been demonstrated. Cases of vaginal erosion caused by tape infections have been described, but none has been associated with human papillomavirus (HPV) infection. We report the first case of vaginal exposure in a woman who underwent a midurethral sling procedure for SUI after HPV colonization.

Insight into new potential targets for the treatment of overactive bladder and detrusor overactivity.

Although overactive bladder (OAB) and detrusor overactivity (DO) are not synonyms, they share therapeutic options and partially underlying physiopathological mechanisms. The aim of this overview is to give insight into new potential targets for the treatment of OAB and DO. A narrative review was done in order to reach this goal. Ageing, pelvic floor disorders, hypersensitivity disorders, morphologic bladder changes, neurological diseases, local inflammations, infections, tumors and bladder outlet obstruction may alter the normal voluntary control of micturition, leading to OAB and DO. The main aim of pharmacotherapy is to restore normal control of micturition, inhibiting the emerging pathological involuntary reflex mechanism. Therapeutic targets can be found at the levels of the urothelium, detrusor muscles, autonomic and afferent pathways, spinal cord and brain. Increased expression and/or sensitivity of urothelial-sensory molecules that lead to afferent sensitization have been documented as a possible pathogenesis of OAB. Targeting afferent pathways and/or bladder smooth muscles by modulating activity of ligand receptors and ion channels could be effective to suppress OAB.

An overview on mixed action drugs for the treatment of overactive bladder and detrusor overactivity.

OBJECTIVES: To provide an overview on the efficacy, tolerability, safety and health-related quality of life (HRQoL) of drugs with a mixed action used in the treatment of overactive bladder (OAB). EVIDENCE ACQUISITION: MEDLINE database and abstract books of the major conferences were searched for relevant publications from 1966 to 2011 and using the key words 'overactive bladder', 'detrusor overactivity', 'oxybutynin', 'propiverine', and 'flavoxate'. Two independent reviewers considered publications for inclusion and extracted relevant data, without performing a meta-analysis. EVIDENCE SYNTHESIS: Old and conflicting data do not support the use of flavoxate, while both propiverine and oxybutynin were found to be more effective than placebo in the treatment of OAB. Propiverine was at least as effective as oxybutynin but with a better tolerability profile even in the pediatric setting. Overall, no serious adverse event for any product was statistically significant compared to placebo. Improvements were seen in HRQoL with treatment by the oxybutynin transdermal delivery system and propiverine extended release. CONCLUSIONS: While there is no evidence to suggest the use of flavoxate in the treatment of OAB, both oxybutynin and propiverine appear efficacious and safe. Propiverine shows a better tolerability profile than oxybutynin. Both drugs improve HRQoL of patients affected by OAB. Profiles of each drug and dosage differ and should be considered in making treatment choices.

Evaluating urinary continence and preoperative predictors of urinary continence after robot assisted laparoscopic radical prostatectomy.

PURPOSE: We evaluated urinary continence using a validated questionnaire in a series of consecutive patients who underwent robot assisted laparoscopic radical prostatectomy, and identified the preoperative predictors of the return to urinary continence. MATERIALS AND METHODS: The clinical records of 308 consecutive patients who underwent robot assisted laparoscopic radical prostatectomy for clinically localized prostate cancer at a tertiary academic center were prospectively collected. All patients were continent before surgery. Urinary continence was evaluated using the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form instrument. All of the patients reporting no leak in response to the question, "How often do you leak urine?" were defined as continent. RESULTS: A total of 273 patients (90%) were continent 12 months after robot assisted laparoscopic radical prostatectomy. Continent patients were significantly younger (61.4 +/- 6.4 vs 64.1 +/- 6.1 years, p = 0.02) than those who were incontinent. On univariable regression analysis patient age at surgery (OR 1.075, p = 0.024) and Charlson comorbidity index (OR 1.671, p = 0.007) were significantly associated with 12-month continence status. On multivariable analysis age (OR 1.076, p = 0.027) and Charlson comorbidity index (OR 1.635, p = 0.009) were independent predictors of continence rates. CONCLUSIONS: Using the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form 90% of patients undergoing robot assisted laparoscopic radical prostatectomy reported no urine leak 12 months after surgery. Patient age at surgery and Charlson comorbidity index were independent predictors of the return to urinary continence, whereas notably no variable related to prostate cancer was significantly correlated with urinary continence.

Robot-assisted radical cystectomy with totally intracorporeal urinary diversion: surgical and early functional outcomes through the learning curve in a single high-volume center.

The aim of the study is to report surgical and early functional outcomes of first 100 patients undergoing robot-assisted radical cystectomy (RARC) with totally intracorporeal urinary diversion (ICUD) in a single center. The main surgeon (A.P.) attended a modular training program at a referring center mentored by a worldwide-recognized robotic surgeon (P.W.). The program consisted of: (a) 10 h of theoretical lessons; (b) video session (c) step-by-step in vivo modular training. Each procedure was performed as taught, without any technique variation. Demographics, intra-operative data and post-operative complications, along with early functional outcomes, were recorded for each patient. We retrospectively evaluated the first consecutive 100 patients submitted to RARC with totally ICUD from July 2015 to December 2018. Median age at surgery was 69 years (IQR 60-74). 52 (52%), 32 (32%), and 17 (17%) patients received orthotopic neobladder, ileal conduit and uretero-cutaneostomy, respectively. Median operative time was 410 min. A median number of lymph nodes retrieved were 27 and median estimated blood loss was 240 mL with median hospitalization time of 7 days. All procedures were completed successfully without open conversion. A statistically significant improvement was found in the late (30-90 post-operative days) post-operative complications (p = 0.02) and operative time for urinary derivation. At multivariate logistic regression model ASA score ≥ 3 (OR = 4.2, p = 0.002) and number of lymph nodes retrieved (OR = 1.16, p = 0.02) were found to be predictors of 90-day complications. An adequate modular training is paramount to obtain successful results and reduce the learning curve of RARC, as demonstrated by our experience.

How accurate are present risk group assignment tools in penile cancer?

OBJECTIVES: To evaluate the accuracy of the predictive models available to estimate the risk of lymph node metastases and cancer-specific survival in patients with squamous cell carcinoma of the penis. METHODS: A nonsystematic review of the literature was performed searching MEDLINE in January 2008. RESULTS: Most of the authors select patients for early inguinal lymphadenectomy according to the pathologic extension of the primary tumor and its histologic grade, as recommended by the EAU Guidelines and the Solsona risk groups. Although the Solsona risk groups performed slightly better, both risk groups had low predictive accuracy. A nomogram including eight clinical and pathologic variables (tumor thickness, microscopic growth pattern, Broder's grade, presence of vascular or lymphatic embolization, infiltrations of the corpora cavernosa, corpus spongiosum or urethra, and the clinical stage of groin lymph nodes) was developed to estimate the risk of lymph node involvement at follow-up. Two nomograms are currently available able to estimate the 5-year cancer-specific survival probabilities of the patients. The first nomogram included the clinical lymph node stage and the same pathological variables of the primary tumor at penectomy, while the pathological stage of the lymph nodes replaced the clinical one in the second model. All the 3 nomograms had good prognostic accuracy. CONCLUSIONS: Both the Solsona and EAU risk group assessment had low prognostic accuracy, although the Solsona risk groups performed slightly better. The nomograms designed to predict the risk of lymph node metastases showed and cancer-specific survival had good prognostic accuracy but their external validation is still lacking.

A new training model for robot-assisted urethrovesical anastomosis and posterior muscle-fascial reconstruction: the Verona training technique.

A training model is usually needed to teach robotic surgical technique successfully. In this way, an ideal training model should mimic as much as possible the "in vivo" procedure and allow several consecutive surgical simulations. The goal of this study was to create a "wet lab" model suitable for RARP training programs, providing the simulation of the posterior fascial reconstruction. The second aim was to compare the original "Venezuelan" chicken model described by Sotelo to our training model. Our training model consists of performing an anastomosis, reproducing the surgical procedure in "vivo" as in RARP, between proventriculus and the proximal portion of the esophagus. A posterior fascial reconstruction simulating Rocco's stitch is performed between the tissues located under the posterior surface of the esophagus and the tissue represented by the serosa of the proventriculus. From 2014 to 2015, during 6 different full-immersion training courses, thirty-four surgeons performed the urethrovesical anastomosis using our model and the Sotelo's one. After the training period, each surgeon was asked to fill out a non-validated questionnaire to perform an evaluation of the differences between the two training models. Our model was judged the best model, in terms of similarity with urethral tissue and similarity with the anatomic unit urethra-pelvic wall. Our training model as reported by all trainees is easily reproducible and anatomically comparable with the urethrovesical anastomosis as performed during radical prostatectomy in humans. It is suitable for performing posterior fascial reconstruction reported by Rocco. In this context, our surgical training model could be routinely proposed in all robotic training courses to develop specific expertise in urethrovesical anastomosis with the reproducibility of the Rocco stitch.

Systematic review and meta-analysis of non RCT's on health related quality of life after radical cystectomy using validated questionnaires: Better results with orthotopic neobladder versus ileal conduit.

PURPOSE: The current literature on the impact of different urinary diversions on patients' health related quality of life (HR-QoL) showed a marginally better quality of life scores of orthotopic neobladder (ONB) compared to ileal conduit (IC). The aim of this study was to update the review of all relevant published studies on the comparison between ONB and IC. MATERIALS AND METHODS: Studies were identified by searching multiple literature databases, including MEDLINE, CINAHL, the Cochrane Library, PubMed Data were synthesized using meta-analytic methods conformed to the PRISMA statement. RESULTS: The current meta-analysis was based on 18 papers that reported a HR-QoL comparison between IC and ONB using at least a validate questionnaire. Pooled effect sizes of combined QoL outcomes for IC versus ONB showed a slight, but not significant, better QoL in patients with ONB (Hedges' g = 0.150; p = 0.066). Patients with ileal ONB showed a significant better QoL than those with IC (Hedges' g = 0.278; p = 0.000); in case series with more than 65% males, ONB group showed a slight significant better QoL than IC (Hedges' g = 0.190; p = 0.024). Pooled effects sizes of all EORTC-QLQ-C30 aspects showed a significant better QoL in patients with ONB (Hedges' g = 0.400; p = 0.0000). CONCLUSIONS: This meta-analysis of not-randomized comparative studies on the impact of different types of urinary diversions on HR-QoL showed demonstrated a significant advantage of ileal ONB compared to IC in terms of HR-QoL.

Molecular analysis of the androgen receptor gene in testicular cancer.

Testicular cancer (TC) is the most common solid tumour in white males aged 20-34 years, and its incidence has doubled over the past 40 years. Some risk factors for TC have been proposed, such as cryptorchidism, infertility and testicular dysgenesis. However, the causes of TC remain still largely unknown. Recently a genetic basis for TC has been proposed, but specific genetic alterations have not been identified. The risk of TC is markedly increased in subjects with androgen insensitivity and some authors have suggested that mutations in the androgen receptor (AR) gene or disorders of CAG and GGC repeats could be related to TC. However, definitive data have not been produced. In this study, we analysed the AR gene for mutations and CAG and GGC triplets in exon 1 in 123 patients affected by TC. In three patients (2.3%) we found a mutation in the AR gene, two of which represent a novel mutation. Evaluation of CAG and GGC repeat numbers showed no difference with respect to controls when these variables were analysed separately. However, when joint distributions of CAG and GGC were considered, we found that the combination CAG=20/GGC=17 was significantly more frequent in TC patients (8.1%) with respect to controls (1.7%, P<0.05). Furthermore, we observed that in TC subjects, differently from controls, the joint analysis of CAG and GGC showed a statistically significant dependence among these variable repeats. In conclusion, our data show for the first time a high prevalence of AR gene mutations in patients affected by TC and suggest that some CAG/GGC combinations might be more frequently associated with an increased risk of TC.

Bladder tissue biomechanical behavior: Experimental tests and constitutive formulation.

A procedure for the constitutive analysis of bladder tissues mechanical behavior is provided, by using a coupled experimental and computational approach. The first step pertains to the design and development of mechanical tests on specimens from porcine bladders. The bladders have been harvested, and the specimens have been subjected to uniaxial cyclic tests at different strain rates along preferential directions, considering the distribution of tissue fibrous components. Experimental results showed the anisotropic, non-linear and time-dependent stress-strain behavior, due to tissue conformation with fibers distributed along preferential directions and their interaction phenomena with ground substance. In detail, experimental data showed a greater tissue stiffness along transversal direction. Viscous behavior was assessed by strain rate dependence of stress-strain curves and hysteretic phenomena. The second step pertains the development of a specific fiber-reinforced visco-hyperelastic constitutive model, in the light of bladder tissues structural conformation and experimental results. Constitutive parameters have been identified by minimizing the discrepancy between model and experimental data. The agreement between experimental and model results represent a term for evaluating the reliability of the constitutive models by means of the proposed operational procedure.

Pharmacological analysis of 5-hydroxytryptamine effects on electrically stimulated human isolated urinary bladder.

1. 5-Hydroxytryptamine (5-HT) is able to potentiate the contractions induced by electrical field stimulation of pieces of human isolated urinary bladder. On the basis of available selective 5-HT agonists and antagonists, we have further investigated the receptors involved and their site of action. 2. 5-HT produced a concentration-dependent increase of the contractile response to electrical field stimulation from 0.1 nM to 1 microM. At higher concentrations (up to 100 microM) the effect decreased. These activities were mimicked by a variety of 5-HT agonists, for which the following rank order of potency was found: 5-HT greater than alpha-methyl 5-HT greater than 5-methoxytryptamine greater than 5-carboxamidotryptamine greater than 2-methyl 5-HT much greater than GR 43175. In addition the gastro-prokinetics agents metoclopramide, cisapride and the 5-HT3 antagonist ICS 205-930 behaved as 5-HT agonists, their EC50 values being 2.3, 0.3, and 0.5 (microM) respectively. 3. The 5-HT potentiating effect was resistant to antagonism by ondansetron (1 microM) and cyanopindolol (1 microM), selective 5-HT3 and 5-HT1A/1B antagonists respectively. The 5-HT2 antagonists ketanserin (1 microM), spiperone (1 microM) and methysergide (1 microM) also showed a weak inhibitory activity. Methiothepin (0.1-1 microM) antagonized only the inhibitory effect of 5-HT. Metoclopramide (0.1-1 microM), cisapride (0.01-0.1 microM) and ICS 205-930 (0.3-3 microM) all produced a rightward displacement of the 5-HT response curve with concomitant reduction of the maximum response. The pA2 values calculated were 7.4, 8.5 and 7.0 respectively. The antagonism of metoclopramide was receptor specific and was not apparently related to interactions with dopaminergic activity since domperidone showed no antagonism of 5-HT, and metoclopramide, itself, did not antagonize the potentiating effect of prostaglandin F2a.4. The receptor involved in the potentiating effect of 5-HT may be located prejunctionally because 5-HT did not potentiate responses to acetylcholine (ACh) or electrical field stimulation with the parameters of direct muscle excitation. Also, since the 5-HT potentiating effect was blocked by atropine, it may be attributed to a release of ACh.5. This study suggests that in the human urinary bladder 5-HT causes two opposite effects on the contractile response to electrical field stimulation. A potentiating effect at low concentrations due to an interaction with an atypical receptor, different from the classical 5-HT1, 5-HT2 or 5-HT3 subtypes and an inhibitory effect at greater concentrations probably due to an interaction with 5-HT1-like receptors. The possibility that this atypical receptor possesses some characteristics of those found in other isolated preparations like guinea-pig ileum, rat oesophagus and mouse embryo colliculi neurones is discussed.

Evidence for the presence of both pre- and postjunctional P2-purinoceptor subtypes in human isolated urinary bladder.

1. In order to characterize P2-purinoceptor(s) in human urinary bladder the contractile effects of ATP and its slowly-hydrolyzable analogues alpha, beta-methylene ATP (alpha, beta-MeATP) and beta, gamma-methylene ATP (beta, gamma-MeATP) were investigated on human detrusor strips taken from patients undergoing cystectomy for bladder carcinoma. 2. Serial concentration-response curves (SCRC) for ATP, alpha, beta-MeATP and beta, gamma-MeATP were constructed with an interval of 25 min between two successive doses to avoid tachyphylaxis. ATP (10 microM-10 mM) induced a phasic contraction, which was very rapid in onset. The dose-response curve to ATP appeared not to be monophasic: at the lower concentrations (10-300 microM) the curve was shallow, whilst at high concentrations (1-10 mM) the curve was steeper. The magnitude of the response obtained at the highest concentration tested (10 mM) was only 21.1 +/- 2.8% (mean +/- s.e. mean; n = 4) of the KCl (100 mM)-induced contraction. 3. alpha, beta-MeATP (0.3 microM-1 mM) and beta, gamma-MeATP (10 microM-1 mM) elicited a phasic contraction with a time course similar to that exhibited by ATP. The magnitude of the response obtained at the highest concentration tested (1 mM) was 70.3 +/- 6.3% for alpha, beta-MeATP (n = 10) and 27.9 +/- 4.5% for beta, gamma-MeATP (n = 8) of KCl (100 mM)-induced contraction. The rank order of potency was alpha, beta-MeATP > beta, gamma-MeATP > ATP. A plateau of response could not be achieved by any of these agonists. 4. The P2-purinoceptor antagonist, suramin (10-300 microM), dose-dependently antagonized only the lower part of alpha,beta-MeATP dose-response curve. Data were analysed in terms of dose-ratio estimated at two levels of response (10% and 35% of KC1 100 mM-induced contraction). At 10% of KCl response the Schild plot slope was 0.98 and the estimated pKB was 5.85, whereas using the dose-ratio at the 35% level of the KCl response, the Schild plot was not linear suggesting an interaction of alpha,beta-MeATP with a heterogeneous receptor population.5. The putative P2-purinoceptor antagonist, Coomassie Brilliant Blue G (CB-G) at 0.3 and 1 l micro M(n = 5), shifted to the left the alpha,beta-MeATP SCRC. The response at the highest concentration of agonist was potentiated, being equal to 78.8 +/- 11.7% of the KCl (100 mM) response (n = 5). CB-G at 0.3 microM also shifted to the left the beta,upsilon-MeATP SCRC and significantly potentiated the response at 1 mM up to 46.3 +/- 5.6% of KCl 100 mM response (n = 4).6. Pretreatment with terodotoxin (TTX) at 1 microM shifted to the left the alpha,beta-MeATP SCRC but the response to the highest concentration of the agonist was not potentiated, being 73.6 +/- 9.9% of the KCl(100 mM) response (n = 5). TTX (1 micro M) shifted to the left the beta,upsilon-MeATP SCRC and significantly potentiated the response at 1 mM (61.6 +/- 3.1% of KCl response; n = 4).7. The NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) at 100 micro M did not modify the SCRC to either alpha, beta or beta,upsilon-MeATP.8. We conclude that in human detrusor muscle there is a heterogeneity of purinoceptors. The complex antagonism exhibited by suramin suggests the presence not only of Ph-purinoceptors but also of another contractile P2-purinoceptor subtype insensitive to suramin. Moreover, the activity of CB-G and TTX seems to support the existence of a prejunctional P2-purinoceptor subtype inducing the release of one or more inhibitor neurotransmitters.

Pharmacological characterization of thromboxane and prostanoid receptors in human isolated urinary bladder.

1. Cumulative concentration-response curves (CRC) to prostaglandin E1 (PGE1), PGE2, PGD2 and PGF2alpha (0.01-30 microM) and to the thromboxane A2 (TXA2) receptor agonist U-46619 (0.01-30 microM) were constructed in human isolated detrusor muscle strips both in basal conditions and during electrical field stimulation. 2. All the agonists tested contracted the detrusor muscle. The rank order of agonist potency was: PGF2alpha > U-46619 > PGE2 whereas weak contractile responses were obtained with PGD2 and PGE1. Any of the agonists tested was able to induce a clear plateau of response even at 30 microM. 3. The selective TXA2 antagonist, GR 32191B (vapiprost), antagonized U-46619-induced contractions with an apparent pK(B) value of 8.27+/-0.12 (n = 4 for each antagonist concentration). GR 32191B (0.3 microM) did not antagonize the contractile responses to PGF2alpha and it was a non-surmountable antagonist of PGE2 (apparent pK(B) of 7.09+/-0.04; n = 5). The EP receptor antagonist AH 6809 at 10 microM shifted to the right the CRC to U-46619 (apparent pK(B) value of 5.88+/-0.04; n = 4). 4. Electrical field stimulation (20 Hz, 70 V, pulse width 0.1 ms, trains of 5 s every 60 s) elicited contractions fully sensitive to TTX (0.3 microM) and atropine (1 microM). U-46619 (0.01-3 microM) potentiated the twitch contraction in a dose-dependent manner and this effect was competitively antagonized by GR 32191B with an estimated pK(B) of 8.54+/-0.14 (n = 4 for each antagonist concentration). PGF2alpha in the range 0.01-10 microM (n = 7), but not PGE2 and PGE1 (n = 3 for each), also potentiated the twitch contraction of detrusor muscle strips (23.5+/-0.3% of KCl 100 mM-induced contraction) but this potentiation was unaffected by 0.3 microM GR 32191B (n = 5). 5. Cumulative additions of U-46619 (0.01-30 microM) were without effect on contractions induced by direct smooth muscle excitation (20 Hz, 40 V, 6 ms pulse width, trains of 2 s every 60 s, in the presence of TTX 1 microM; n = 3). Moreover, pretreatment of the tissue with 0.3 microM U-46619 did not potentiate the smooth muscle response to 7 microM bethanecol (n = 2). 6. We concluded that TXA2 can induce direct contraction of human isolated urinary bladder through the classical TXA2 receptor. Prostanoid receptors, fully activated by PGE2 and PGF2alpha are also present. All these receptors are probably located post-junctionally. The rank order of agonist potency and the fact that GR 32191B, but not AH6809, antagonized responses to PGE2 seem to indicate the presence of a new EP receptor subtype. Moreover, we suggest the presence of prejunctional TXA2 and FP receptors, potentiating acetylcholine release from cholinergic nerve terminals.

Use of prostaglandin E1 in the treatment of sexual impotence after heart transplantation: initial clinical experience.

Many patients report problems of impotence after heart transplantation, which definitely impairs their quality of life. Ten men, with a mean age of 41 years, were evaluated for persistent erection problems after heart transplantation by measurement of nocturnal penile tumescence using a Rigiscan. Three men had a positive response, and their disturbances were therefore considered to have a psychological basis; seven men had a negative or only weakly positive response, and their impotence was attributed to organic causes. To all patients, intracavernous injections of an initial dose of 10 to 20 micrograms of prostaglandin E1 were administered as first-choice treatment. Nine patients obtained a firm, lasting erection 2 to 5 minutes after injection, with no relevant side effects. The patients were then instructed to self-administer the drug before intercourse, and some were able to return to spontaneous sexual activity at various intervals. Intracavernous injection of prostaglandin E1 seems to be an effective treatment of erectile impotence in heart transplant recipients; it is well tolerated with no side effects and considerably improves the patient's quality of life.

Diagnosis and significance of idiopathic overactive bladder.

OBJECTIVES: To offer a critical overview of the basis for the International Continence Society (ICS) classification of detrusor instability, to summarize current diagnostic methodologies, and to outline the etiologic factors that should be excluded in the diagnosis of idiopathic overactive bladder. METHODS: The current ICS definitions of overactive bladder are discussed. Issues related to the diagnosis of detrusor instability (DI) are addressed through a review of the literature. RESULTS: The term idiopathic overactive bladder reflects the present lack of knowledge concerning vesicourethral function and dysfunction. The term is used to apply to a wide spectrum of different conditions that may have a common final pathophysiologic pathway. This heterogeneous group of conditions could be subdivided on the basis of presumptive etiopathogenesis, urodynamic patterns, and response to treatment. The diagnosis of DI, its rate of detection, and its urodynamic patterns depend on the type of urodynamic test used and the way the test is performed. The ICS definitions of DI have been called into question by the results of studies using urodynamic tests in addition to, or instead of, provocative cystometry--for instance, ambulatory urodynamics, urethrocystometry, the ice-water test, and evaluation of the voiding phase. The literature supports a broadening of the ICS criteria for excluding all known causes of DI when establishing the diagnosis of idiopathic overactive bladder. CONCLUSIONS: Appropriate longitudinal studies, using contemporary urodynamic tests and knowledge, are needed to improve the identification of subsets of patients with overactive bladder who have different prognoses and outcomes. The ICS definitions and classification should be updated.

Pediatric nephroscope for percutaneous renal stone removal.

A new 17-F nephroscope was used for percutaneous renal stone management. It appeared useful in reducing the possible main vascular injuries after percutaneous nephrolithotomy. Personal experience with pediatric as well as selected adult cases is presented.