Examining the upper urinary tract in patients with hematuria-time to revise the CT urography protocol?

BACKGROUND: Three-phase CT urography (CTU) is the gold standard for evaluating the upper urinary tract in patients with hematuria. We aimed to evaluate the accuracy of CTU for detecting upper urothelial cell carcinomas (UCC) in patients with hematuria and negative cystoscopy. Secondly, we aimed to determine the tumor visibility on each CTU phase. MATERIAL AND METHODS: This retrospective study included all patients with hematuria referred to CTU after a negative cystoscopy during 2016 and 2017. The original CTU reports were dichotomized as negative or positive. All patient charts were reviewed after a minimum of 18-month follow-up in order to register missed cancers. The results of biopsies and clinical follow-up were used as the reference standard. Two reviewers retrospectively evaluated the tumor visibility of each CT sequence in all true-positive CTUs. RESULTS: We included 376 patients with hematuria who underwent CTU after a negative cystoscopy. Macroscopic and microscopic hematuria occurred in 87% (327) and 13% (49), respectively. The incidence of upper urothelial cell carcinoma was 1.9% (7), and the sensitivity of CTU was 100% (95% CI, 59-100), specificity was 99% (95% CI, 98-100), positive predictive value was 88% (95% CI, 47-99), and negative predictive value was 100% (95% CI, 99-100). The accuracy was 99% (95% CI, 90-100). All UCCs were visible on the nephrographic phase for both reviewers. CONCLUSION: CTU is highly accurate for detecting upper UCCs. All cases were seen on the nephrographic phase. This suggests that the CTU protocol can be simplified. KEY POINTS: • CT urography is highly accurate for detecting upper urothelial cell carcinomas. • All cancers were seen on the nephrographic phase. • All cancers were detected in patients with macroscopic hematuria.

Phosphodiesterase type 5 expression in human and rat lower urinary tract tissues and the effect of tadalafil on prostate gland oxygenation in spontaneously hypertensive rats.

INTRODUCTION: In humans, prostate phosphodiesterase type 5 inhibitors (PDE5) expression was prominently localized in the endothelial and smooth muscle cells of the vascular bed, suggesting a possible action of PDE5 inhibitors (PDE5i) on prostate blood flow. AIM: To investigate PDE5 expression in human and rat lower urinary tract (LUT) tissues, including vasculature, and determine the effects of PDE5 inhibition with tadalafil on prostatic blood perfusion. MAIN OUTCOME MEASURES: Human vesicular-deferential arteries (which originate from the inferior vesical artery, the main arterial source of blood supply to the bladder and prostate) were analyzed for PDE5 expression and activity. The effects of tadalafil on prostate oxygenation were studied in spontaneously hypertensive rats (SHR), characterized by ischemia/hypoxia of the genitourinary tract. METHODS: PDE5 expression was evaluated by quantitative reverse transcription-polymerase chain reaction and immunohistochemistry. SHR were treated with tadalafil (2 mg/kg/day) for 1, 7, or 28 days and compared with untreated SHR and the unaffected counterpart Wistar-Kyoto (WKY) rats. Prostate oxygenation was detected by Hypoxyprobe-1 and hypoxia markers (hypoxia-inducible factor-1α[HIF-1α] and endothelin-1 type B [ETB]) immunostaining. RESULTS: Human vesicular-deferential artery expressed high levels of PDE5, similar to corpora cavernosa, immunolocalized in the endothelial and smooth muscle layer. In these arteries, tadalafil inhibited cyclic guanosine monophosphate breakdown (half maximal inhibitory concentration (IC(50) ) in the low nanomolar range, as in corpora cavernosa) and increased the relaxant response to sodium nitroprusside. SHR prostate resulted markedly hypoxic (hypoxyprobe immunopositivity) and positive for HIF-1α and ETB, while tadalafil treatment restored oxygenation to WKY level at each time point. The mRNA expression of the HIF-1α target gene, BCL2/adenovirus E1B 19 kDa interacting protein 3, was significantly increased in SHR prostate and partially restored to WKY level by tadalafil. CONCLUSION: Human vesicular-deferential artery is characterized by a high expression and activity of PDE5, which was inhibited by tadalafil in vitro. In SHR, tadalafil increases prostate tissue oxygenation, thus suggesting a possible mechanism through which PDE5i exert beneficial effects on LUT symptoms.

Sexual steroids in urogynecology.

The decline in sex hormone levels that accompanies the menopause has substantial effects on the tissues of the urogenital system, leading to atrophic changes. These changes can have negative effects on sexual and urinary function. The authors evaluate the repercussion of hypoestrogenism and sexual steroids on some elements of the pelvic floor and lower urinary tract. They summarize their research work and review significant published papers. They emphasize the changes in urinary mucosae, periurethral vessels, muscular layer, connective tissue, gene expression, autonomic nervous system receptors, as well as the main clinical aspects involved.

Association of lower urinary tract symptoms and chronic ischaemia of the lower urinary tract in elderly women and men: assessment using colour Doppler ultrasonography.

OBJECTIVES: To investigate, using transrectal colour Doppler ultrasonography, (TRCDUS) whether perfusion of the bladder and prostate is reduced in elderly patients with lower urinary tract symptoms (LUTS), common in later life, as experimental data suggest that chronic ischaemia has a key role in the development of LUTS. PATIENTS, SUBJECTS AND METHODS: In 32 elderly patients with LUTS (12 women, mean age 82.3 years, group 1; and 20 men, 79.4 years, group 2) perfusion of the bladder neck (in women) and of the bladder neck and prostate (in men) was measured using TRCDUS and the resistive index (RI) and colour pixel density (CPD) determined, assessed by a TRUS unit and special software. To assess the age-related effect two control groups of 10 young healthy women (mean age 42.3 years, group 3) and 10 age-matched healthy men (mean age 41.5 years, group 4) were also enrolled. RESULTS: Irrespective of gender, there was markedly lower bladder perfusion in elderly patients with LUTS than in the younger subjects. The mean (SD) RI of the bladder neck in group 1, of 0.88 (0.06), and group 2, of 0.80 (0.08), was higher than in control groups 3, of 0.62 (0.05), and group 4, of 0.64 (0.09). The results were similar for the CPD measurements. The frequency of daily and nightly micturition showed a strong negative correlation with perfusion in the urinary bladder. CONCLUSION: In elderly patients with LUTS there was decreased perfusion of the bladder neck and prostate when assessed using TRCDUS. Therefore, decreased perfusion in the urinary bladder might be responsible for the development of LUTS with advancing age.

Effect of laparoscopic hysterectomy on the vascularization of the lower urinary tract.

INTRODUCTION: The aim of this prospective study was to evaluate the changes in the vascularization of the lower urinary tract following laparoscopic hysterectomy (LH). METHODS: Seventy women undergoing LH not under the indication of a uterine myoma were included. All subjects underwent urinalysis, pelvic examination, and introital color Doppler ultrasonography and completed a urinary questionnaire before and 6 months after LH. One-hour pad tests and urodynamic studies were performed in clinically incontinent women pre- and postoperatively. RESULTS: Evaluation of the Doppler velocimetric parameters of bladder neck and periurethral vessels before and after LH, including number of vessels, pulsatility index, systolic peak, and minimum diastole, revealed no statistically significant differences (p > 0.05). In addition, the prevalence of stress urinary incontinence (SUI) decreased significantly from 37.1% (n = 26) preoperatively to 17.1% (n = 12) postoperatively (p < 0.01). A total of 19 patients reported no further SUI following LH. Their urinary leakages on the pad tests had all <10 g before surgery. When we analyzed the data of the women reporting no further SUI (n = 19) and de novo SUI (n = 5) following LH, the changes in the pulsatility index also showed no significant difference from the pre-LH values (p > 0.05). CONCLUSIONS: The results of our study suggest that LH has little impact on the blood flow of bladder neck and urethra. Although some women experienced relief of the symptoms of mild or de novo SUI after LH, this being unrelated to changes in the vascularization of the lower urinary tract.

Neonatal arterial hypertension in nephro-urological malformations in a tertiary care hospital.

An increase in the survival of neonates with antenatal diagnosis of malformations was achieved by the recent technical advances in neonatal intensive care units. The aim of this article is to describe the experience with neonatal arterial hypertension, in newborns with nephro-urological malformations, in a tertiary care referral Nursery, in a period of 4 years. Newborn medical records from the Nursery Annex to the Maternity of Hospital das Clinicas, School of Medicine, University of Sao Paulo, with the diagnosis of nephro-urological malformations and systemic arterial hypertension (SAH) at hospital discharge, in a period from January 1999 to January 2003, were retrospectively analysed. Among 10.278 live newborns in the studied period, 15 (0.15%) newborns were compatible with our inclusion criteria. Of these 15 newborns, 12 (80%) were male and three were premature (20%). In relation to aetiology, 13 (87%) showed urological malformations, 1 (6%) chronic renal insufficiency secondary to kidney dysplasia and one (6%) autosomal recessive polycystic kidney disease. SAH control was achieved with monotherapy in eight patients (53%), five patients (33%) needed an association of two drugs (calcium-channel blocker and angiotensin converting enzyme (ACE) inhibitor), one child used three types of antihypertensive drugs (calcium-channel blocker, ACE inhibitor and hydrochlorothiazide) for pressoric control and one child's blood pressure (BP) was controlled exclusively by peritoneal dialysis. The incidence of nephro-urological malformations in our service during the studied period was 0.89%. SAH incidence among these newborns was 19%. Our data reinforce previous studies pointing to the necessity to consider children with nephro-urological malformations as a risk group for SAH, who should have the BP evaluated since the neonatal period.

[Anatomical and surgical meaning of the ureters during the performance of radical hysterectomy].

During the pelvic surgery ureters are dissected until they flow to the bladder. For this reason surgen must be knowleadgable about the anatomy of the vesico-ureteral unit and the blood supply of the ureters,because the majority of the early and late complications, especially following pelvic irradiation,are related to the function of kidneys and ureters. In the present review attention is paid on the ureters as an anatomical marker during the performance of radical hysterectomy and on the possible intraoperative complications, identification and avoidance of ureteral injuries,as well. Authors also discussed on the management of ureteral damages.

[Anatomical and surgical meaning of the bladder during the performance of radical hysterectomy].

During the performance of radical hysterectomies in the everyday practice, oncologists continuously face difficulties and problems related to the urinary tract at the time of early and late postoperative period and occasionally intraoperatively. Bladder complications are hypo- and atonia, which may lead to hydroyreter and hydronephrosis. These hypo- and atonia sometimes delate adjuvant therapies and this influences therapeutic results. Thus in the present review are reported the blood supply, nerve structures and bladder function, which preserving may result in less complications after radical hysterectomy

The Role of Nitric Oxide and Hydrogen Sulfide in Urinary Tract Function.

This MiniReview focuses on the role played by nitric oxide (NO) and hydrogen sulfide (H2 S) in physiology of the upper and lower urinary tract. NO and H2 S, together with carbon monoxide, belong to the group of gaseous autocrine/paracrine messengers or gasotransmitters, which are employed for intra- and intercellular communication in almost all organ systems. Because they are lipid-soluble gases, gaseous transmitters are not constrained by cellular membranes, so that their storage in vesicles for later release is not possible. Gasotransmitter signals are terminated by falling concentrations upon reduction in production that are caused by reacting with cellular components (essentially reactive oxygen species and NO), binding to cellular components or diffusing away. NO and, more recently, H2 S have been identified as key mediators in neurotransmission of the urinary tract, involved in the regulation of ureteral smooth muscle activity and urinary flow ureteral resistance, as well as by playing a crucial role in the smooth muscle relaxation of bladder outlet region. Urinary bladder function is also dependent on integration of inhibitory mediators, such as NO, released from the urothelium. In the bladder base and distal ureter, the co-localization of neuronal NO synthase with substance P and calcitonin gene-related peptide in sensory nerves as well as the existence of a high nicotinamide adenine dinucleotide phosphate-diaphorase activity in dorsal root ganglion neurons also suggests the involvement of NO as a sensory neurotransmitter.

Effect of a single treatment with tadalafil on blood flow in lower urinary tract tissues in rat models of bladder overdistension/emptying and abdominal aorta clamping/release.

Impaired blood flow in lower urinary tract (LUT) tissues is a pathophysiological cause of LUT symptoms. We investigated the effects of the phosphodiesterase 5 (PDE5) inhibitor tadalafil on the sustained decrease in bladder blood flow (BBF) and time-dependent changes in BBF and prostate blood flow (PBF) resulting from ischemia/reperfusion in two rat models. In a rat model of bladder overdistension/emptying (O/E), the bladder was overdistended by saline infusion and emptied after 2h. Tadalafil was administered intraduodenally immediately after emptying. In a rat model of clamping/release (C/R), the abdominal aorta was clamped for 2h after a single oral dose of tadalafil and then the clamp was released. BBF in O/E and C/R rats and PBF in C/R rats were measured by laser Doppler flow imaging. BBF decreased on overdistension and partially recovered after emptying. A progressive decrease in BBF was observed after O/E, and this was prevented by tadalafil treatment. Both BBF and PBF decreased during clamping of the abdominal aorta and partially recovered after clamp removal. Oral pretreatment with tadalafil partially or completely prevented the decreases in BBF and PBF not only after clamp removal but also during clamping. PDE5 mRNA was highly expressed in the bladder and the supporting vasculature. Tadalafil inhibited the O/E-induced decrease in BBF and the C/R-induced time-dependent decreases in BBF and PBF. PDE5 inhibition by tadalafil may improve both BBF and PBF.

Mechanisms of urinary tract infection.

Most urinary tract infections begin as a cystitis secondary to decreased host resistance brought on by disruption of tissue integrity or a decrease in blood supply to the bladder. In the female, infrequent voiding and the uninhibited bladder are the most common causes of urinary tract infection and are best treated by healthy voiding regimens; while in the male, structural and functional obstructive uropathy are most often associated with urinary tract infection and are alleviated by lowering the high intravesical pressures via surgical or medical measures. The concept that host resistance is the determinant of infection rather than the organism has permitted the use of clean, intermittent self-catheterization; clean intermittent self-dilatation; and transurethral diverticulectomy in the therapy of a host of urologic disease syndromes.

Regional differences in the effects of capsaicin and tachykinins on motor activity and vascular permeability of the rat lower urinary tract.

The effects of capsaicin, substance P (SP) and neurokinin A (NKA) on motor activity and vascular permeability was investigated in the rat lower urinary tract (bladder dome and neck, proximal urethra and ureters). Capsaicin produced contractions of the rat bladder dome and neck and of the proximal urethra in vitro, which were unaffected by tetrodotoxin and abolished by ganglionectomy. SP and NKA were almost equipotent in producing a contraction of the rat isolated bladder dome or neck and urethra. However, the maximal response to NKA was about twice that of SP on the urethra and bladder neck. Capsaicin did not affect motility of the unstimulated rat isolated ureter, while NKA or SP activated rhythmic contractions, NKA being about 850 times more potent than SP. Either capsaicin or field stimulation produced a transient inhibition of the NKA-activated rhythmic contractions of the rat isolated ureter which was prevented by capsaicin-desensitization. The capsaicin-(1 microM) or field stimulation-induced inhibition of NKA-activated rhythmic contractions of the rat isolated ureter were unaffected by removal of pelvic ganglia but abolished by cold storage (72 h at 4 degrees C). Intravenous capsaicin induced an inflammatory response (Evans blue leakage) in the bladder, proximal urethra and ureters in vivo. Plasma extravasation was greater in the ureters, urethra and bladder neck than in the dome. SP, NKA and histamine produced a dose-dependent dye leakage in all segments of the rat urinary tract, the response being slightly greater in the bladder neck than in the dome. The capsaicin-induced inflammatory response was abolished by systemic capsaicin-desensitization and reduced, to a variable extent, by pelvic ganglionectomy, in the various tissues examined. Topical application of tetrodotoxin on the bladder dome failed to affect the capsaicin-induced plasma extravasation in the urinary bladder. These findings indicate that chemoceptive, capsaicin-sensitive nerves are present throughout the whole rat lower urinary tract and their activation determines a variety of visceromotor responses and an increase of vascular permeability. In various instances the response to capsaicin may be explained by the action of tachykinins but some effects may involve other sensory neuropeptides.

Species-related variations in the effects of capsaicin on urinary bladder functions: relation to bladder content of substance P-like immunoreactivity.

1. The effect of capsaicin on bladder motility in vivo (urethane anaesthesia) and in vitro, plasma extravasation (Evans blue leakage technique) and content of substance P-like immunoreactivity (SP-LI) of the urinary bladder was investigated in various mammalian species. 2. Systemic capsaicin desensitization (rat and hamster, 50 mg/kg s.c. 4 days before; guinea-pig 55 mg/kg s.c. 4-7 days before) increased bladder capacity in rats and guinea-pigs and reduced voiding efficiency in guinea-pigs. All other urodynamic parameters were unaffected in both rats, guinea-pigs and hamsters. 3. Reflex bladder voiding was abolished by spinal cord transection in anaesthetized rats and hamsters. On the other hand, hexamethonium-(20 mg/kg i.v.)sensitive voiding contractions were obtained in response to saline filling 45 min from cord transection in guinea-pigs, indicating a profound interspecies variation in the basic organization of micturition. 4. Exposure to capsaicin (1 microM) produced a contraction of the isolated bladder from rats, guinea-pigs (dome) and mice. Capsaicin produced only a slight contractile response in the guinea-pig bladder base. The motor response to capsaicin of the rat, guinea-pig and mouse bladder exhibited marked desensitization, suggesting a specific effect on sensory nerves. On the other hand, capsaicin (1 microM) produced a slight relaxation of the hamster isolated bladder but this effect was reproducible at 1-2 h intervals, suggesting an unspecific effect. Capsaicin (1-10 microM) did not affect motility of strips from the dome or the base of the rabbit bladder. 5. Intravenously administered capsaicin produced a marked plasma extravasation (Evans blue leakage) in the lower urinary tract of rats, mice and guinea pigs. In rats but not guinea-pigs the reaction in the bladder base was greater than in the dome. In hamsters intravenous capsaicin failed to induce any significant Evans blue leakage in the lower urinary tract. 6. SP-LI was detected in the lower urinary tract of rats, guinea-pigs, rabbits and mice but not hamsters. Bladder SP-LI was depleted by systemic capsaicin desensitization in rats, guinea-pigs and mice. Reverse phase HPLC indicated that all the immunoreactive material co-eluted with authentic substance P or its oxidized form. 7. These findings indicate that noticeable species-related differences exist with regard to the functions mediated by the capsaicin-sensitive neurons in the urinary bladder.

Effect of prostaglandin E2 and indomethacin on blood flow in the lower urinary tract of the rabbit.

The effect of the cyclooxygenase system on lower urinary tract blood flow was investigated in a standardized rabbit model with empty bladder. Twenty-eight New-Zealand white rabbits were separated into 3 groups. The first group received 1 mg per kg b.w. s.c. daily of PGE2 for 4 days. The second group received 10 mg per kg of indomethacin perorally daily for 7 days. The third group served as controls. The experiments were undertaken in general anaesthesia. Regional blood flow of the lower urinary tract was measured with 141Ce-labeled microspheres and plasma volume was assessed by the equilibrium distribution of 125I-labeled fibrinogen in tissues. Peroral treatment with indomethacin caused a significant increase in blood flow in the trigone. No difference in whole bladder blood flow was found and no differences were found among groups with respect to plasma volume.

[Role of urodynamics correction in combined therapy of children with urinary infection]. / Znachenie korrektsii urodinamiki v kompleksnoi terapii detei s infektsiei mochevyvodiashchikh putei.

The authors propose differentiated complexes of therapy of children with urinary infection. These complexes include medicines (M-cholinolytics, antihypoxic drugs and drugs improving microcirculation) and low-invasive therapy. Clinical experience is reported for 4 boys and 40 girls with microbial-inflammatory urinary diseases. Standard urodynamic tests were made in all the patients before and after the course of therapy. Three variants of driptan effects on the urinary bladder were identified: M-cholinolytic, spasmolytic and mixed (larger volume and lower intravesical hypertension). Some of the patients experienced standard endoscopic reflux correction with the use of synthetic hydrophilic gel. Control urodynamic examinations 3 months after the treatment showed that functional disorders were reduced. Treatment efficacy was assessed with home flowmetry. Thus, combined therapy of microbial-inflammatory diseases with parallel correction of lower urinary tracts urodynamics by M-cholinolytics improves treatment results. Courses of antibacterial and uroceptic therapy should be followed by non-invasive monitoring to reveal urodynamic disorders, define dysfunction type and perform an additional treatment with mediators in combination with physiotherapeutic procedures.

Accessory or additional renal arteries show no relevant effects on the width of the upper urinary tract: a 64-slice multidetector CT study in 1072 patients with 2132 kidneys.

OBJECTIVE: The aim of this study was to find out on an unselected patient group whether crossing vessels have an influence on the width of the renal pelvis and what independent predictors of these target variables exist. METHODS: In this cross-sectional study, 1072 patients with arterially contrasted CT scans were included. The 2132 kidneys were supplied by 2736 arteries. RESULTS: On the right side, there were 293 additional and accessory arteries in 286 patients, and on the left side there were 304 in 271 patients. 154 renal pelves were more than 15 mm wide. The greatest independent factor for hydronephrosis on one side was hydronephrosis on the contralateral side (p<0.0001 each). Independent predictors for the width of the renal pelvis on the right side were the width of the renal pelvis on the left, female gender, increasing age and height; for the left side, predictors were the width of the renal pelvis on the right, concrements, parapelvic cysts and great rotation of the upper pole of the kidney to dorsal. Crossing vessels had no influence on the development of hydronephrosis. Only anterior crossing vessels on the right side are associated with widening of the renal pelvis by 1 mm, without making it possible to identify the vessel as an independent factor in multivariate regression models. CONCLUSION: The width of the renal pelvis on the contralateral side is the strongest independent predictor for hydronephrosis and the width of the renal pelvis. There is no link between crossing vessels and the width of the renal pelvis.

Persistent detrusor overactivity after transurethral resection of the prostate is associated with reduced perfusion of the urinary bladder.

OBJECTIVES: To elucidate, in patients with benign prostatic hyperplasia (BPH), how often detrusor overactivity (DOA) is persistent after transurethral resection of the prostate (TURP) and if perfusion of the lower urinary tract influences postoperative outcomes. PATIENTS AND METHODS: Fifty men with urodynamically confirmed DOA and bladder outlet obstruction due to BPH had a TURP. Before and 1 year after TURP the International Prostate Symptom Score (IPSS), quality of life (QoL) score, prostate-specific antigen (PSA) level and total prostatic volume (TPV) were evaluated. Also, the lower urinary tract was evaluated using pressure-flow studies and transrectal colour Doppler ultrasonography to assess the vascular resistive index (RI) as a variable of the perfusion of the lower urinary tract. RESULTS: After TURP the IPSS, QoL score, PSA level and TPV decreased. Cystometric measurements showed that in 15 (30%) patients DOA was persistent after TURP. The mean (sd) maximum urinary flow rate increased from 9.20 (4.03) to 15.98 (4.62) mL/s and postvoiding residual urine volumes decreased from 109.38 (73.71) to 29.24 (45.00) mL. When men with persistent DOA (15 patients; group 1) were compared with those with no DOA after TURP (35; group 2) there was a statistically significantly higher RI of the bladder vessels in group 1, at 0.86 (0.068) than in group 2, at 0.68 ( 0.055) (P < 0.001). CONCLUSIONS: Persistent DOA in men after TURP seems to be associated with increased vascular resistance of the bladder vessels with subsequent reduced perfusion and hypoxia.

Ureteral obstruction by a rare venous anomaly: a case report.

Aberrant blood vessels are a rare cause of ureteral obstruction. A case is reported of right upper ureteral obstruction that simulated radiologically a retrocaval ureter. At operation the ureter was obstructed by an aberrant vein going from the right spermatic vein to the inferior vena cava. The obstruction was relieved by dividing this vessel. Aberrant blood vessels should be considered in the differential diagnosis of extrinsic ureteral obstruction.

Functional assessment of the sympathetic innervation of the microcirculation of the lower urinary tract: a preliminary report.

This paper presents preliminary data on a new method for testing the sympathetic innervation of the urothelium. A flexible laser Doppler probe was introduced into the urethra of two females and two male subjects. The percentage fall in laser Doppler flux following generalized sympathetic stimulation by taking an inspiratory gasp was measured. This resulted in 36%, 32%, 68% and 34% mean drop in urothelial blood flux. In the female subjects, the probe was advanced into the bladder and the procedure repeated, and the gasp resulted in 60% and 83% drop in flux. With laser Doppler fluxmetry, fall in microcirculatory blood flow associated with a generalized increase in sympathetic tone, therefore can be demonstrated. This method may be useful in the assessment of the integrity of the sympathetic innervation of the urothelium in patients with suspected autonomic dysfunction of the genitourinary tract.