A survey of ethically challenging issues in urological practice.

PURPOSE: We surveyed ethical attitudes among urological and nonurological practitioners, allowing for thought and discussion regarding ethical issues in a larger audience. MATERIALS AND METHODS: With input from an academic urologist, a senior medical student and a hospital ethics committee member, a survey was created which asked for multiple choice responses to 3 demographic questions (practice type, age, location) and 10 ethically challenging clinical questions. Surveys were distributed online or via mail to 5 groups including academic urologists, urologists in private practice, medical students, hospital risk managers/attorneys and members of a bioethical society. Surveys were analyzed according to demographic variables. RESULTS: Surveys were sent out to 1,447 individuals and 340 responses were received (24%). There were statistically significant differences in the responses to several questions based on practice type, age and practice location. There was a lack of consistency in answer choices with greater than 50% agreeing on a single answer choice for only 4 of 10 questions (40%). CONCLUSIONS: This is the first study to our knowledge which attempts to objectively categorize ethical attitudes in a broad based survey of urologists and nonurologists, and challenges members of our profession to study their own responses to these ethical issues.

Prostaglandin E2mediates spontaneous rhythmic contraction in rabbit detrusor muscle.

INTRODUCTION: The purpose of this investigation was to determine if prostaglandin E2(PGE2) is produced by rabbit detrusor free of urothelium and demonstrate that PGE2 is responsible for the generation of spontaneous rhythmic contraction (SRC). METHODS: A bioassay was performed in which contraction frequency in strips of rabbit detrusor was compared before and after addition of superfusate from incubating sections of rabbit detrusor. Specificity was determined by testing the effects of SC-51089, a PGE2(EP1) antagonist. Effects on development of tension were determined in artery segments after treatment with increasing doses of PGE2, PGF2α, and TXA2, and a section of femoral artery was used as a negative control. Confirmation of PGE2 production was then determined using EIA kits. RESULTS: Increased rhythmic frequency was identified after superfusate from a section of rabbit detrusor free of urothelium was added to strips of detrusor from the same animal. Additional experiments demonstrated that rhythmic frequency generated after treatment with PGE2 was significantly reduced after treatment with SC-51089. In artery smooth muscle, prostaglandin dose response experiments demonstrated that only TXA2 induced contraction at physiologic doses (<10⁻7M). As a negative control, subsequent treatment of a section of femoral artery with detrusor superfusate failed to increase tension, confirming a lack of TXA2 production. EIA confirmed that PGE2 production increased by 4.8-fold in strips of detrusor free of urothelium after 15 minutes of incubation and that this production was blocked by ibuprofen and a COX-1 inhibitor. CONCLUSIONS: Rabbit detrusor produces PGE2 which is the most likely mediator of SRC.

Potential for control of detrusor smooth muscle spontaneous rhythmic contraction by cyclooxygenase products released by interstitial cells of Cajal.

Interstitial cells of Cajal (ICCs) have been identified as pacemaker cells in the upper urinary tract and urethra, but the role of ICCs in the bladder remains to be determined. We tested the hypotheses that ICCs express cyclooxygenase (COX), and that COX products (prostaglandins), are the cause of spontaneous rhythmic contraction (SRC) of isolated strips of rabbit bladder free of urothelium. SRC was abolished by 10 microM indomethacin and ibuprofen (non-selective COX inhibitors). SRC was concentration-dependently inhibited by selective COX-1 (SC-560 and FR-122047) and COX-2 inhibitors (NS-398 and LM-1685), and by SC-51089, a selective antagonist for the PGE-2 receptor (EP) and ICI-192,605 and SQ-29,548, selective antagonists for thromboxane receptors (TP). The partial agonist/antagonist of the PGF-2alpha receptor (FP), AL-8810, inhibited SRC by approximately 50%. Maximum inhibition was approximately 90% by SC-51089, approximately 80-85% by the COX inhibitors and approximately 70% by TP receptor antagonists. In the presence of ibuprofen to abolish SRC, PGE-2, sulprostone, misoprostol, PGF-2alpha and U-46619 (thromboxane mimetic) caused rhythmic contractions that mimicked SRC. Fluorescence immunohistochemistry coupled with confocal laser scanning microscopy revealed that c-Kit and vimentin co-localized to interstitial cells surrounding detrusor smooth muscle bundles, indicating the presence of extensive ICCs in rabbit bladder. Co-localization of COX-1 and vimentin, and COX-2 and vimentin by ICCs supports the hypothesis that ICCs were the predominant cell type in rabbit bladder expressing both COX isoforms. These data together suggest that ICCs appear to be an important source of prostaglandins that likely play a role in regulation of SRC. Additional studies on prostaglandin-dependent SRC may generate opportunities for the application of novel treatments for disorders leading to overactive bladder.

Robotic Ureteral Reconstruction Using Buccal Mucosa Grafts: A Multi-institutional Experience.

BACKGROUND: Minimally invasive treatment of long, multifocal ureteral strictures or failed pyeloplasty is challenging. Robot-assisted buccal mucosa graft ureteroplasty (RBU) is a technique for ureteral reconstruction that avoids the morbidity of bowel interposition or autotransplantation. OBJECTIVE: To evaluate outcomes for RBU in a multi-institutional cohort of patients treated for revision ureteropelvic junction obstruction and long or multifocal ureteral stricture at three tertiary referral centers. DESIGN, SETTING, AND PARTICIPANTS: This retrospective study involved data for 19 patients treated with RBU at three high-volume centers between October 2013 and July 2016. SURGICAL PROCEDURE: RBU was performed using either an onlay graft after incising the stricture or an augmented anastomotic repair in which the ureter was transected and re-anastomosed primarily on one side, and a graft was placed on the other side. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Preoperative, intraoperative, and postoperative variables and outcomes were assessed. A descriptive statistical analysis was performed. RESULTS AND LIMITATIONS: The onlay technique was used for 79%, while repair was carried out using the augmented anastomotic technique for the remaining cases. The reconstruction was reinforced with omentum in 95% of cases. The ureteral stricture location was proximal in 74% and mid in 26% of cases. A prior failed ureteral reconstruction was present in 53% of patients. The median stricture length was 4.0cm (range 2.0-8.0), operative time was 200min (range 136-397), estimated blood loss was 95ml (range 25-420), and length of stay was 2 d (range 1-15). There were no intraoperative complications. At median follow-up of 26 mo, the overall success rate was 90%. CONCLUSIONS: RBU is a feasible and effective technique for managing complex proximal and mid ureteral strictures. PATIENT SUMMARY: We studied robotic surgery for long ureteral strictures using grafts at three referral centers. Our results demonstrate that robotic buccal mucosa graft ureteroplasty is a feasible and effective technique for ureteral reconstruction.

Adjustable passive length-tension curve in rabbit detrusor smooth muscle.

Until the 1990s, the passive and active length-tension (L-T) relationships of smooth muscle were believed to be static, with a single passive force value and a single maximum active force value for each muscle length. However, recent studies have demonstrated that the active L-T relationship in airway smooth muscle is dynamic and adapts to length changes over a period of time. Furthermore, our prior work showed that the passive L-T relationship in rabbit detrusor smooth muscle (DSM) is also dynamic and that in addition to viscoelastic behavior, DSM displays strain-softening behavior characterized by a loss of passive stiffness at shorter lengths following a stretch to a new longer length. This loss of passive stiffness appears to be irreversible when the muscle is not producing active force and during submaximal activation but is reversible on full muscle activation, which indicates that the stiffness component of passive force lost to strain softening is adjustable in DSM. The present study demonstrates that the passive L-T curve for DSM is not static and can shift along the length axis as a function of strain history and activation history. This study also demonstrates that adjustable passive stiffness (APS) can modulate total force (35% increase) for a given muscle length, while active force remains relatively unchanged (4% increase). This finding suggests that the structures responsible for APS act in parallel with the contractile apparatus, and the results are used to further justify the configuration of modeling elements within our previously proposed mechanical model for APS.

A mechanical model for adjustable passive stiffness in rabbit detrusor.

Strips of rabbit detrusor smooth muscle (DSM) exhibit adjustable passive stiffness characterized by strain softening: a loss of stiffness on stretch to a new length distinct from viscoelastic behavior. At the molecular level, strain softening appears to be caused by cross-link breakage and is essentially irreversible when DSM is maintained under passive conditions (i.e., when cross bridges are not cycling to produce active force). However, on DSM activation, strain softening is reversible and likely due to cross-link reformation. Thus DSM displays adjustable passive stiffness that is dependent on the history of both muscle strain and activation. The present study provides empirical data showing that, in DSM, 1) passive isometric force relaxation includes a very slow component requiring hours to approach steady state, 2) the level of passive force maintained at steady state is less if the tissue has previously been strain softened, and 3) tissues subjected to a quick-release protocol exhibit a biphasic response consisting of passive force redevelopment followed by force relaxation. To explain these and previously identified characteristics, a mechanical model for adjustable passive stiffness is proposed based on the addition of a novel cross-linking element to a hybrid Kelvin/Voigt viscoelastic model.

Mechanical properties of electrospun fibrinogen structures.

Fibrin and fibrinogen have a well-established track record in tissue engineering due to their innate ability to induce improved cellular interaction and subsequent scaffold remodeling compared to synthetic scaffolds. Use of fibrinogen as a primary scaffold component, however, has been limited by traditional processing techniques that render scaffolds with insufficient mechanical properties. The goal of this study was to demonstrate, based on mechanical properties, that electrospun fibrinogen overcomes these limitations and can be successful as a tissue engineering scaffold or wound dressing. Electrospun fibrinogen scaffolds were characterized for fiber diameter and pore area and subsequently tested for uniaxial mechanical properties while dry and hydrated. In addition, uniaxial mechanical testing was conducted on scaffolds treated to regulate scaffold degradation in serum-containing media by supplementing the media with aprotinin or cross-linking the scaffolds with glutaraldehyde vapor. A linear relationship between electrospinning solution concentration and measured fiber diameter was seen; fiber diameters ranged from 120 to 610 nm over electrospinning concentrations of 80 to 140 mg/ml fibrinogen, respectively. Pore areas ranged from 1.3 microm(2) to 13 microm(2) over the same fibrinogen concentrations. Aprotinin in the culture media inhibited scaffold degradation in a predictable fashion, but glutaraldehyde vapor fixation produced less reliable results as evidenced by mechanical property testing. In conclusion, the mechanical characteristics of electrospun fibrinogen strongly support its potential use as a tissue engineering scaffold or wound dressing.

The adolescent varicocele: to treat or not to treat.

Whether to treat adolescents with varicocele is controversial because over 80% of adult varicoceles are not associated with infertility. Most physicians agree that treating all adolescents with varicocele and subjecting boys to unnecessary surgery is inappropriate,costly, and not without ethical considerations. Waiting until patients present as adults with potentially irreversible infertility, however, is equally unacceptable. Pediatricians and urologists must determine which adolescents are at greatest risk for future fertility problems and warrant early intervention. This article reviews the current literature surrounding adolescent varicocele and offers recommendations for identifying individuals who would most benefit from treatment.

Obstructive uropathy: an important cause of chronic renal failure in children.

Care of individuals with renal failure continues to impose a tremendous burden on our national health care budget. Chronic renal failure is the final common denominator of a multiplicity of pathologic processes, some of which progress silently over years. Of these, obstructive uropathy is a prominent cause of kidney failure, accounting for 16.5% of all pediatric renal transplants in 1997. The pathophysiology of obstructive uropathy is reviewed as the basis for a differential diagnosis. In view of the significant role played by obstructive uropathy in the development of renal failure, early and definitive treatment of this clinical entity is imperative.

Treatment strategy for the adolescent varicocele.

A varicocele is a dilatation of the testicular vein and the pampiniform venous plexus within the spermatic cord. Although rare in pediatric populations, the prevalence of varicoceles markedly increases with pubertal development. Varicoceles are progressive lesions that may hinder testicular growth and function over time and are the most common and correctable cause of male infertility. Approximately 40% of men with primary infertility have a varicocele, and more than half of them experience improvements in semen parameters after varicocelectomy. The decision to treat adolescents with varicocele is a controversial one. The task for pediatricians and urologists is to identify those adolescents who are at greatest risk for infertility in adulthood, in an effort to offer early surgical intervention to those most likely to benefit.

Ureteroscopy for the treatment of urolithiasis in children.

PURPOSE: Ureteroscopy for treating urolithiasis in prepubertal children has become more common with the advent of smaller instruments. We reviewed our experience with ureteroscopy for urolithiasis in this cohort of patients as well as the literature using this treatment modality in children. MATERIALS AND METHODS: Between 1994 and 2000 we performed 27 ureteroscopic stone extractions in 25 children. Ureteroscopy was done in a manner similar to that in adults. Ureteral dilation was performed when necessary to access the ureter. A stent was placed postoperatively if there was significant ureteral trauma. RESULTS: Of the 25 children 13 were male and 12 were female. Average age was 9.2 years (range 3 to 14). Stones were 2 to 12 mm. in greatest diameter (average 6). Of the 27 procedures the ureteral orifice was dilated before stone treatment in 15 (56%), while in 19 (70%) a stent was placed afterward. No intraoperative and 2 postoperative complications were identified. Overall 92% of the children were rendered stone-free after 1 procedure and 100% were stone-free after 2. CONCLUSIONS: Ureteroscopy for urolithiasis in prepubertal children is safe and effective. Routine ureteral dilation and ureteral stent placement are not always necessary in these patients.

Pediatric renal pelvic fullness: an ultrasonographic dilemma.

PURPOSE: We conducted a prospective study to define normal renal pelvic size in children. MATERIALS AND METHODS: Institutional Review Board approved consent was obtained to perform renal ultrasound during excretory urography (IVP) scheduled for medical management. Mean patient age (17 females, 11 males) was 5.2 years. Renal ultrasound was conducted concurrent with 10-minute IVP. RESULTS: Fifty kidneys were imaged with 51 collecting systems. IVP defined 44 collecting systems as normal. Mean anteroposterior pelvic diameter on sonography for these 44 systems was 3.3 mm. One normal collecting system on IVP had a diameter greater than 10 mm on ultrasound (14 mm). No sonographic caliceal dilatation was seen in any kidney appearing normal on IVP. The 7 dilated systems on IVP had a mean ultrasound diameter of 17.1 mm. Two dilated collecting systems smaller than 10 mm in diameter on sonography had caliceal distention on ultrasound. CONCLUSIONS: Normal renal pelvis threshold diameter was 10 mm in asymptomatic children. We recommend further evaluation in children with caliceal dilatation and/or dilatation of the anteroposterior renal pelvis greater than 10 mm. Using these criteria, no system appearing abnormal on IVP would have been missed.