Correction of experimentally produced vesicoureteric reflux in the piglet by intravesical injection of Teflon.

Vesicoureteric reflux was produced in eight piglets by opening their bladders and slitting the anterior intravesical wall of the ureter. Cystography confirmed the presence of bilateral reflux in six piglets and unilateral reflux in two. Six to eight weeks later the bladder was again opened and Teflon paste injected in the space behind the intravesical ureter, thereby creating a support for the submucosal ureter. Cystography four to six weeks after injection of Teflon paste showed absence of reflux in all animals. Intravenous pyelography showed obstruction at the vesicoureteric junction in only one of the 14 treated ureters and this was later confirmed at necropsy. Animals were followed up from one to six months and then were killed. Gross examination of the vesicoureteric region showed a well circumscribed subureteric Teflon mass of firm consistency, retaining its shape and position at the site of the injection. Histological examination showed encapsulation of the implant by a thin layer of fibrous tissue and a foreign body granulomatous reaction with histiocytes and giant cells within the implant. Hence it is technically feasible to correct experimentally produced vesicoureteric reflux in the piglet by intravesical injection of Teflon paste--a relatively inert material. It may now be possible to treat vesicoureteric reflux in man by endoscopic injection of Teflon behind the intravesical ureter.     

Vesico-ureteric Reflux after Renal Transplantation

The uretero-vesical junction has been examined by micturating cystography in 20 patients after renal transplantation. Intravenous pyelograms were used to investigate the upper urinary tract in 13 of the patients. Persistent urinary infection did not occur in patients without vesico-ureteric reflux. However, both those with reflux of their own and the transplant ureters had persistent infection. When reflux affected the tunnelled transplanted ureter there was no infection, but two patients without a tunnel implant had a persistent urinary infection.     

Management of vesicoureteral reflux

Four cases of vesicoureteral reflux are discussed by prominent pediatric urologists. The condition can range from minimal reflux into the distal ureter to massive reflux causing tortuosity of the ureter and hydronephrosis. Treatment options range from medical management to tapering of the ureter with reimplantation. The cross-trigonal technique is popular among pediatric urologists, and the Politano-Leadbetter technique is a very successful technique that has stood the test of time. The extravesical approach to ureteral reimplantation reduces morbidity, shortens hospital stays, reduces medical costs, and maintains the high success rates of the intravesical techniques. Subureteric injection of bulking agents to correct the reflux holds promise as an alternative to open surgery, but presents the challenge of identifying the ideal bulking agent.     

Part III – Treatment of Ureterovesical Reflux

Of 134 girls with demonstrable ureterovesical reflux, 61 (105 ureters) had the reflux surgically corrected with an overall surgical cure rate of 97 percent. In the remaining 73 children (112 ureters), the reflux was treated conservatively with medical management alone. During the follow-up period no significant differences were demonstrated in the overall incidence of urinary tract infection; two years following corrective operation or medical treatment more than 50 percent of both medically and surgically treated children were still experiencing infections. A pronounced decrease, however, occurred in the incidence of clinical pyelonephritis among the surgically treated group. Following correction of reflux, the incidence of pyelonephritis was similar in both medically and surgically treated cases and was approximately the same as that found in a comparable group of children without reflux.In approximately two-thirds of refluxing renal units in which there was evidence of clubbing and scarring before medical or surgical therapy, deterioration progressed during the follow-up period. In most of these cases infection control was felt to be inadequate with episodes of clinical pyelonephritis occurring during the period of medical management, or, in the surgically treated group, occurring just before corrective operation and the scar appearing within two years after operation.The majority of renal units in which calyceal clubbing and parenchymal scarring was present had the most severe grades of reflux.     

Computer assisted laparoscopic pneumovesical ureter reimplantation a.m. Cohen: initial experience in a pig model

To assess the feasibility of a new variant of laparoscopic Cohen cross-trigonal ureter reimplantation in vesico-ureteral reflux (VUR) using telesurgical equipment. VUR was induced in 8 female pigs by transurethral unroofing of the ureteric orifices. Three months later the reflux was verified by a cystography. A cross-trigonal ureter reimplantation a.m. Cohen was performed by laparoscopic access to the bladder using the da Vinci telesurgical system. The 12 mm camera port was placed below the umbilicus, two 8 mm working ports for the robotic system were placed lateral to the rectus muscles and an additional port for assistance between camera and right working port. The outcome was assessed 3 months later by a new cystography. The operative time for a single reimplantation varied from 45 to 90 minutes. In all pigs the reflux disappeared after the procedure, which was complicated by a postoperative port hernia in two animals. Laparoscopic transvesical ureter reimplantation using telesurgical equipment is a feasible method in the few cases this procedure is indicated. The advantage of the robotic equipment is the better access to submucosal tunneling of the ureter and the intravesical suturing of the anastomosis indicated by shorter operative time and success rates similar to the open procedure.     

Development and differentiation of the ureteric bud into the ureter in the absence of a kidney collecting system

Six1-/- mice were found to have apparently normal ureters in the absence of a kidney, suggesting that the growth and development of the unbranched ureter is largely independent of the more proximal portions of the UB which differentiates into the highly branched renal collecting system. Culture of isolated urinary tracts (from normal and mutant mice) on Transwell filters was employed to study the morphogenesis of this portion of the urogenital system. Examination of the ureters revealed the presence of a multi-cell layered tubule with a lumen lined by cells expressing uroplakin (a protein exclusively expressed in the epithelium of the lower urinary tract). Cultured ureters of both the wild-type and Six1 mutant become contractile and undergo peristalsis, an activity preceded by the expression of alpha-smooth muscle actin (alphaSMA). Treatment with a number of inhibitors of signaling molecules revealed that inhibition of PI3 kinase dissociates the developmental expression of alphaSMA from ureter growth and elongation. Epidermal growth factor also perturbed smooth muscle differentiation in culture. Moreover, the peristalsis of the ureter in the absence of the kidney in the Six1-/- mouse indicates that the development of this clinically important function of ureter (peristaltic movement of urine) is not dependent on fluid flow through the ureter. In keeping with this, isolated ureters cultured in the absence of surrounding tissues elongate, differentiate and undergo peristalsis when cultured on a filter and undergo branching morphogenesis when cultured in 3-dimensional extracellular matrix gels in the presence of a conditioned medium derived from a metanephric mesenchyme (MM) cell line. In addition, ureters of Six1-/- urinary tracts (i.e., lacking a kidney) displayed budding structures from their proximal ends when cultured in the presence of GDNF and FGFs reminiscent of UB budding from the wolffian duct. Taken together with the above data, this indicates that, although the distal ureter (at least early in its development) retains some of the characteristics of the more proximal UB, the growth and differentiation (i.e., development of smooth muscle actin, peristalsis and uroplakin expression) of the distal non-branching ureter are inherent properties of this portion of the UB, occurring independently of detectable influences of either the undifferentiated MM (unlike the upper portion of the ureteric bud) or more differentiated metanephric kidney. Thus, the developing distal ureter appears to be a unique anatomical structure which should no longer be considered as simply the non-branching portion of the ureteric bud. In future studies, the ability to independently analyze and study the portion of the UB that becomes the renal collecting system and that which becomes the ureter should facilitate distinguishing the developmental nephrome (renal ontogenome) from the ureterome.     

Abnormalities in ureter and kidney development in mice given acetazolamide-amiloride or dimethadione (DMO) during embryogenesis.

These experiments more accurately define the effects of the combination acetazolamide-amiloride or a single dose of dimethadione (DMO), the active metabolite of trimethadione, on the development of the ureter. When acetazolamide-amiloride was administered in C57BL/6NCrlBR mice on day 9, 9.5, or 10 of gestation (plug = day 0) a second ureter was formed, anterior to the original ureter, inducing a second kidney. The second ureter then fails to make a connection with the developing bladder and remains attached to the mesonephric duct. The mesonephric duct becomes the vas deferens in the male and deteriorates completely in the female leading to either a restricted ureter or a blocked ureter depending on the sex of the fetus. Administration of a single dose of DMO between gestational day 9 and 10.3 produced both renal agenesis and ureters of varying lengths. Some ureters were of normal length with a tuft of one or two nephrons at their tip, while others were one half or one quarter of their normal length. In some instances the ureter was completely absent. The reason for this strong effect on the ureter is unknown.     

Dysphonia Due to Unilateral Nerve Paralysis—Treatment by the Intracordial Injection of Synthetics—A Preliminary Report

The injection treatment of unilateral recurrent vocal cord nerve paralysis, successfully performed 40 years ago with paraffin, has recently been reintroduced with non-reactive synthetics. Improvement in the voice far and above that which can be achieved by voice therapy or any practicable surgical procedure has been demonstrated by several investigators. The technique is relatively simple, and there are no significant untoward reactions. Judging from experimental and clinical studies with these inert materials when introduced into other parts of the body, adverse long range effects are not likely to occur in the larynx.Eleven of 12 patients treated by injection of silicone or Teflon paste had substantial improvement in vocal quality and strength. Silicone was absorbed slowly from the injection site and the improvement was not enduring; when Teflon was used, it stayed at the site and the improvement was sustained.     

Analysis of electrical activities of the junction region of the ureter with bladder and surrounding zones in rats

Spontaneous electrical activity of the rat ureters per bladder zone was studied. In area of ureter connection with bladder, slow-wave activity was revealed. In bladder bordering ureter zone, rapid spike activity was found that was fully correlated with the genesis of upper located fluctuation processes.     

Management of Localized Prostate Cancer and an Incidental Ureteral Duplication With Upper Pole Ectopic Ureter Inserting into the Prostatic Urethra

Ectopic ureters are rare congenital malformations of the renal system that most commonly present in females. It is extremely rare to encounter an ectopic ureter in an older man undergoing radical prostatectomy. We report herein a case of a 66-year-old man with prostate cancer and a complete duplication of the left renal collecting system, with an upper pole ectopic ureter and associated normal functioning renal parenchyma entering into the prostatic urethra. This anomaly was incidentally discovered on preoperative magnetic resonance imaging of the prostate. Open radical retropubic prostatectomy and a left ureteroureterostomy were performed.Key words: Prostate cancer, Ectopic ureter, Prostatic urethra, Prostatectomy, UreteroureterostomyEctopic ureters are rare and occur in about 1 of 1900 live births.¹ Over 85% of ectopic ureters are associated with duplicated systems and most commonly present in females. Ectopic ureters present 2 to 12 times less frequently in males than in females, and in males are most commonly associated with a single collecting system.² Ectopic ureters inserting into the prostatic urethra often present with obstruction and/or urinary tract infections. Few cases of ectopic ureters entering into the prostatic urethra as an incidental finding in men undergoing radical prostatectomy for prostate cancer have been reported in the literature.^3,4 This case report describes a patient with prostate cancer and an asymptomatic upper pole ectopic ureter inserting into the prostatic urethra associated with normal functioning renal parenchyma demonstrated on preoperative mercaptoacetyltriglycine (MAG-3) renogram, magnetic resonance imaging (MRI), and computed tomography (CT). We discuss the treatment plan for this patient and give an overview of ectopic ureters.     

Age-related changes of elements in human ureter

To elucidate changes of the ureter with aging, the authors investigated age-related changes of element contents in human ureters. The subjects consisted of seven men and seven women, ranging in age from 61 to 97 yr. The contents of calcium, sulfur, and iron in the ureters increased progressively with aging, whereas the contents of phosphorus and magnesium did not increase with aging. Significant relationships were found both between calcium and sulfur contents and between calcium and iron contents in the ureters, but not between calcium and either phosphorus or magnesium contents. It was noteworthy that a significant relationship was also found between sulfur and iron contents in the ureters. It remains uncertain whether calcium forms a compound with sulfur or iron in aged human ureters or not.     

The inhibitory effects of prostaglandin E1 on guinea-pig ureter.

Prostaglandin E1 (PGE1) hyperpolarized the smooth muscle cells of guinea-pig ureter in normal Krebs solution and was without effect on ureters depolarized in KCl Krebs, PGE1 inhibited both electrically induced contractions and K+-induced contractures of the ureters. Conditions that favored greater tension development by the ureters, namely, high [K+] or high [Ca-2+] reduced the inhibitory effects of PGE1 on the K+-induced contractures. Depolarization of guinea-pig ureter with KCl Krebs led to an increase in radio-calcium content of the tissue over a 30 min loading period. This increase in the tissue's radio-calcium content was further increased by PGE1 but not by theophylline, PGE1 was found to have no effect on either total calcium content or the calcium efflux from the tissue. It is suggested that PGE1 exerts its inhibitory action by increasing calcium sequestration at the inner surface of the cell membrane.     

Assessing vesicoureteral reflux in live inbred mice via ultrasound with a microbubble contrast agent

Vesicoureteral reflux (VUR) is a common pediatric anomaly linked to renal scarring and hypertension. Although there are many mouse VUR models, cystograms have previously only been performed in euthanized animals, thus preventing serial assessments for VUR in the same animal and not delineating "live" physiology. Our purpose was to develop a live murine cystogram assay that could be used serially to track reflux. We injected microbubbles via transurethral catheters into bladders of C57BL6/J and C3H/HeJ inbred mouse strains that are known to have low and high VUR rates, respectively. We performed ultrasound to visualize microbubbles in the renal pelvis to determine feasibility of the procedure. We then repeated the microbubble ultrasound using a transducer allowing for visualization of both kidneys and ureters simultaneously and for 3 dimensional (3D) reconstruction. We then performed "euthanized" cystograms on all mice for comparison. C3H/HeJ mice had a strong and persistent microbubble signal in the renal pelvis and ureters bilaterally with low-contrast infusion volumes (<100 μl) and similarly showed bilateral reflux by euthanized cystograms. With larger infused volumes (≥150 μl), C57BL6/J mice had small volumes of microbubbles in the renal pelvis that cleared quickly and did not show reflux on euthanized cystograms. Thus, using animal models of known VUR, we demonstrate the utility of contrast-enhanced ultrasound to visualize reflux in live mice.     

Pharmacology of ureter.

Ureter which performs the important function of transport of urine from kidney to the bladder is not a passive tube, but exhibits characteristic spontaneous (peristaltic) activity. This peristaltic activity is characterized by coordinated muscular contractions, which after originating from a spontaneously active primary pacemaker, situated in the vicinity of the pelvi ureteric junction, propagate downwards along the entire length of the ureter. In addition, the ureter, like the heart, possesses certain cells which become activated when the primary pacemaker is suppressed or there is an interruption of conduction, thereby, acting as latent pacemakers. (1) The peristaltic activity of the ureter is modified by several pharmacologically active substances. Moreover, some of these substances are occasionally able to initiate spontaneous activity even in quiescent ureters. This article briefly reviews the effects of catecholamines (adrenaline, noradrenaline and isoprenaline) and acetylcholine on the ureters of human beings and some domestic and laboratory animals.     

The genetics of urinary tract malformations

In this discussion I have excluded consideration of the genetics of purely renal malformations, such as polycystic kidneys, and of functional disorders of the kidney. Systematic family studies are available for renal agenesis, duplication of the ureters, vesico-ureteric reflux (each probably due to maldevelopment of the ureteric bud), bladder exstrophy and hypospadias as isolated malformations. Renal agenesis has a birth frequency of about 1.2 in 10 000 and the proportion affected of sibs is about 3 per cent. Duplication of the ureter has a birth frequency of about 1 per cent and the proportion affected of sibs and parents of probands is about 12 per cent. Vesico-ureteral reflux also has a prevalence in early childhood of about 1 per cent and the proportion of sibs affected is about 10 per cent. Bladder exstrophy has a birth frequency of about 1 in 20 000 and perhaps about 1 per cent of sibs are affected. Hypospadias has a birth frequency in boys of about 1 in 300 and the proportion affected of brothers is about 10 per cent. Further family studies are needed of these malformations when they occur in isolation. Either the multifactorial threshold model or dominant inheritance with reduced penetrance and varied expressivity would fit the data available.     

Adrenergic regulation of the contractility of the human and canine ureters]

Investigations on the isolated pieces from upper part of human ureters and upper and lower parts of dog ureters were performed. Isometric contractions during electrical stimulation in Lock solution (37 degrees C) and their changes after adrenomimetic drug and adrenoblocking drug perfusion were studied. The pieces of human ureters had more average weight and rest tension, but less isometric tension during rhythmic electrical stimulation and more pronounced hypersodium contracture in contrast to dog ureters. Adrenaline and noradrenaline augmented contractions of human and dog ureters. Isadrin increased the contractility of the upper parts of human ureters and the lower parts of dog ureters, but decreased--the upper segments of dog ureters. Adrenoblocking agents modified the action of adrenomimetics. After blockade of alpha-receptors by phentolamine, isadrin decreased the contractions of all studied pieces of ureters, however, adrenaline decreased contractility of human ureters but increased--dog ureters. It may be proposed, that there are alpha 1 and alpha 2 receptors, that stimulated the contractility of human and dog ureters, beta 1 adrenoreceptors, that inhibited the contractions during blockade of alpha-receptors, and beta 2-receptors, that in these conditions increased the contractions of dog ureter but decreased the contractions of human ureters.     

Feasibility and safety of cryoablation on the porcine ureter using a new balloon cryoprobe

Cryoablation, as a well-characterized technology, has multifarious clinical applications. But few are reported on ureteral endometriosis. Thus, we examined the feasibility and safety of cryotherapy with a novel balloon cryoprobe on ureter in a live porcine model. During the freezing and thawing cycle, temperature was recorded in different parts of the ureter in real-time. Two-minute cryoablation could induce necrosis within range in 1 cm diameter on serosa layer. The temperature respectively dropped to −136.5 °C, −96.1 °C and −17.5 °C at the cryotherapy center, 1 cm and 1.5 cm from center on serosal side. The ureters were harvested immediately, 2 weeks or 3 months after cryotherapy. No perforation, stricture, adhesions, or hydronephrosis was observed. Histopathologic representations of ureters after cryoablation indicated that full thickness necroses of ureters were seen in all samples. The results demonstrated ureteral cryoablation using a novel balloon probe was feasible, safe, and effective. These findings provided us reference before cryoablation could be applied in clinical practice in treating ureteral endometriosis.     

Molecular pathology of murine ureteritis causing obstructive uropathy with hydronephrosis

Primary causes of urinary tract obstruction that induces urine retention and results in hydronephrosis include uroliths, inflammation, and tumors. In this study, we analyzed the molecular pathology of ureteritis causing hydronephrosis in laboratory rodents.F2 progenies of C57BL/6 and DBA/2 mice were studied histopathologically and by comprehensive gene expression analysis of their ureters. Incidence of hydronephrosis was approximately 5% in F2 progenies. Histopathologically, this hydronephrosis was caused by stenosis of the proximal ureter, which showed fibrosis and papillary malformations of the proliferative epithelium with infiltrations of B-cell-dominated lymphocytes. Additionally, CD16-positive large granular leukocytes and eosinophils infiltrated from the ureteral mucosa to the muscular layer. Eosinophilic crystals were characteristically observed in the lumen of the ureter and the cytoplasm of large granular leukocytes, eosinophils, and transitional epithelial cells. Comprehensive gene profiling revealed remarkably elevated expression of genes associated with hyperimmune responses through activation of B cells in diseased ureters. Furthermore, diseased ureters showed dramatically higher gene expression of chitinase 3-like 3, known as Ym1, which is associated with formation both of adenomas in the transitional epithelium and of eosinophilic crystals in inflammatory conditions. The Ym1 protein was mainly localized to the cytoplasm of the transitional epithelium, infiltrated cells, and eosinophilic crystals in diseased ureters.We determined that the primary cause of hydronephrosis in F2 mice was ureteritis mediated by the local hyperimmune response with malformation of the transitional epithelium. Our data provide a novel molecular pathogenesis for elucidating causes of aseptic inflammation in human upper urinary tracts.