Intrinsic Ureteropelvic Junction Obstruction Research Articles

IMMUNOHISTOCHEMICAL EXPRESSION OF C-KIT AND S-100 MARKERS IN URETEROPELVIC JUNCTION OBSTRUCTION AND ITS CORRELATION WITH HISTOPATHOLOGY AND MASSON'S TRICHROME STAINING

Background: Congenital obstructive nephropathy is the principal cause of end stage renal disease (ESRD) in children ( Beneldet al. 2003). Obstructive nephropathy leads to Hydronephrosis, dened clinically by an enlargement of the kidney as a result of urine accumulation in the renal pelvis or calyces. [1,2] Ureteropelvic junction (UPJ) obstruction is the most common cause of hydronephrosis with an estimated incidence of 1 in 1000–1500 newborns ( Changet al. 2004). [2,3] Aims: To evaluate the pathogenesis of congenital ureteropelvic junction obstruction (UPJO) by histopathology, IHC markers CD117 & S100 and special stain Masson's Trichrome. Methods And Materials: The study group consists of 50 Pediatric cases presenting with intrinsic ureteropelvic junction obstruction and 15 patients with Wilms tumor with no UPJO formed the control group. All the cases and controls were subjected to histopathological examination, immunohistochemical staining with markers CD117 & S100 and special stain Masson's Trichrome. Mann – Whitney U test and Pearson's chisquare test were used for statistical analysis. The cases had reduce Results: d CD117 and S100 expression, Irregularity of muscle bers, increased wall thickness & muscle thickness and submucosal collagen deposition compared to controls. Decreased ICC interpreted by Conclusions: decreased CD117, decreased neural innervation interpreted by decreased S100, structural changes - Irregularity of muscle bers arrangement, increased submucosal collagen deposition and increased smooth muscle thickness possibly cause disruption of the mobility of UPJ and lead functional obstruction.

Comparative Proteome Analyses of Ureteropelvic Junction Obstruction and Surrounding Ureteral Tissue

Ureteropelvic junction (UPJ) obstruction is a common problem in children, but its etiology remains unclear. In this study, the proteome profiles of the obstructed segment and its surrounding distal and proximal parts were comparatively evaluated. Twelve children younger than 2 years of age with unilateral intrinsic UPJ obstruction were included. The excised operational tissue was divided into three parts immediately after resection: the obstructed part (Obst), the distal normal ureteral part (Dist), and the proximal part of the obstructed segment (Prox). Proteins extracted from the tissue samples were subjected to two-dimensional gel electrophoresis analysis to identify differentially regulated proteins. Spot analysis revealed that four proteins, namely tropomyosin beta and alpha-1 chains, actin and desmin, were upregulated in Obst in comparison to Dist. A similar analysis between Obst and Prox showed that heat shock protein beta-1 and carbonic anhydrase-1 were upregulated in Obst, while tropomyosin alpha 3 chain and ATP synthase beta were upregulated in Prox. The last comparative analysis between Dist and Prox revealed upregulation of annexin-A5 and annexin-A1 in Dist and vimentin, mitochondrial ATP synthase subunit-beta, peroxiredoxin-2, and apolipoprotein-A1 in Prox. Bioinformatics analysis using the STRING server indicated that the differentially regulated proteins, altogether, point to the changes occurring in muscle filament sliding pathway. When regulations occurring in each group were mutually compared, a change in lipase inhibition activity was detected by STRING. This is the first study scrutinizing changes occurring in protein profiles in UPJ.

Medusa's Curls: Ureteropelvic Junction Obstruction Secondary to Multiple Long Intraluminal Polyps

Fibroepithelial polyps represent a rare cause of intrinsic ureteropelvic junction obstruction in the pediatric population, accounting for less than 5% of cases. Herein, we present this peculiar case of a 10-year-old boy with multiple large intraluminal FEPs resembling Medusa's hair and the challenges associated with its subsequent treatment plan.

Are There Any Differences in the Neural and Extracellular Matrix Proteins Density Between Children and Adults with Intrinsic Ureteropelvic Junction Obstruction?

Are There Any Differences in the Neural and Extracellular Matrix Proteins Density Between Children and Adults with Intrinsic Ureteropelvic Junction Obstruction?

Activated Hedgehog-GLI Signaling Causes Congenital Ureteropelvic Junction Obstruction.

Intrinsic ureteropelvic junction obstruction is the most common cause of congenital hydronephrosis, yet the underlying pathogenesis is undefined. Hedgehog proteins control morphogenesis by promoting GLI-dependent transcriptional activation and inhibiting the formation of the GLI3 transcriptional repressor. Hedgehog regulates differentiation and proliferation of ureteric smooth muscle progenitor cells during murine kidney-ureter development. Histopathologic findings of smooth muscle cell hypertrophy and stroma-like cells, consistently observed in obstructing tissue at the time of surgical correction, suggest that Hedgehog signaling is abnormally regulated during the genesis of congenital intrinsic ureteropelvic junction obstruction. Here, we demonstrate that constitutively active Hedgehog signaling in murine intermediate mesoderm-derived renal progenitors results in hydronephrosis and failure to develop a patent pelvic-ureteric junction. Tissue obstructing the ureteropelvic junction was marked as early as E13.5 by an ectopic population of cells expressing Ptch2, a Hedgehog signaling target. Constitutive expression of GLI3 repressor in Ptch1-deficient mice rescued ectopic Ptch2 expression and obstructive hydronephrosis. Whole transcriptome analysis of isolated Ptch2+ cells revealed coexpression of genes characteristic of stromal progenitor cells. Genetic lineage tracing indicated that stromal cells blocking the ureteropelvic junction were derived from intermediate mesoderm-derived renal progenitors and were distinct from the smooth muscle or epithelial lineages. Analysis of obstructive ureteric tissue resected from children with congenital intrinsic ureteropelvic junction obstruction revealed a molecular signature similar to that observed in Ptch1-deficient mice. Together, these results demonstrate a Hedgehog-dependent mechanism underlying mammalian intrinsic ureteropelvic junction obstruction.

Immunohistochemistry in Ureteropelvic Junction Obstruction and Its Correlation to Postoperative Outcome.

Aim:To investigate the correlation between the status of interstitial cells of Cajal (ICC) in ureteropelvic junction (UPJ) and the resected ureteric margin and the postoperative outcome of Anderson-Hynes pyeloplasty in UPJ obstruction (UPJO) and to compare the ICC in the UPJ and the resected margin of the normal ureter.Materials and Methods:An observational study was conducted over a period of 2 years at the Department of Pediatric Surgery at Niloufer Institute of Women and Child Health. Children with intrinsic UPJO who underwent Anderson-Hynes dismembered pyeloplasty were included in the study. Six months postoperatively, the patients were divided into two groups based on diuretic isotopic renogram using technetium-99m-labeled diethylene triaminepentaacetic acid. Group 1 comprised patients with good surgical outcome. Group 2 comprised patients with a poor outcome. The histologic specimens were evaluated for ICC, and the immunohistochemical findings were correlated with the outcome.Results:Twenty-five patients were included in this study (19 male and 6 female). Seventy-six percent of patients were under the age of 1 year. Group 1 had 23 cases and Group 2 had 2 cases. Out of the two patients with a poor outcome, one had negative grading at the UPJ and one had positive grading. Both these patients had a negative grading at the lower resected margins. More number of patients (24%) had +++ grading at the lower resected margin when compared to the UPJ (8%).Conclusion:This is the first study which correlates the status of ICC in UPJ with the outcome of pyeloplasty in pediatric patients. Both the cases with bad outcome had no ICC at the lower margin of the resected specimen and one case had no ICC at the UPJ. There is a statistically significant difference (P = 0.001) in the number of ICC at the UPJ and the resected margin.

Hydronephrosis: Comparison of extrinsic vessel versus intrinsic ureteropelvic junction obstruction groups and a plea against the vascular hitch procedure

Pediatric ureteropelvic junction obstruction (UPJO) due to an extrinsic crossing vessel (CV) is rare and often remains undiagnosed preoperatively. Vascular hitch procedures are often performed as associated intrinsic obstruction is not expected. We compared data and intravenous urography (IVU) findings of patients with aberrant CV versus those with intrinsic UPJO, all undergoing open dismembered pyeloplasty. Is accurate pre-operative diagnosis of aberrant CV causing extrinsic UPJO possible? To assess differences in the demographic, clinical, radiological, intra-operative features and postoperative improvement after pyeloplasty between patients with a CV and those with only intrinsic UPJO. Prospective study of all children below 12 years with UPJO presenting to a tertiary referral centre and who underwent open Anderson - Hynes dismembered pyeloplasty between 2003 and 2013 was conducted. Pre-operative investigations included serial ultrasonography, renal dynamic [ethylene di-cysteine (EC)] scan and IVU. These were repeated 3 months after pyeloplasty. Pre-operative IVUs of children with CV were compared with the IVUs of an equal number of similar aged children, randomly selected from the intrinsic obstruction group. Pyeloplasty was performed in 643 children during the study period. Data of 33 children with aberrant CVs (mean age 6.99 years) were compared with the remaining 610 children (mean age 3.27 years) with only intrinsic obstruction. Highly significant associations of those with CV included age above 2 years, female gender, associated anomalies, abdominal pain in those above 2 years and poor preoperative function on IVU. Specific IVU features which were statistically highly significant in favor of presence of CV were small, intrarenal and globular flat bottomed pelvis. (Figure) Calyceal dilatation was also more prominent in the CV group. A funnel shaped, extrarenal pelvis was highly significant in favor of intrinsic obstruction. There was associated intrinsic obstruction in addition to CV obstruction in 8 children. All children symptomatically improved after pyeloplasty and did well on long term follow up. The majority showed improvement or stabilization of function on EC scan. With the advent of antenatal ultrasonography, most children with UPJO are detected early. Children with CV tend to present later. This is often detected during surgery. Color Doppler is useful but is operator dependant and not performed routinely. In this study, IVU showed the presence of obstruction and loss of function unlike color Doppler, but also revealed specific diagnostic features not previously reported in literature. This can help in accurate preoperative prediction and avoid endopyelotomy, or a dorsal lumbotomy/retroperitoneal approach. Renal function in CVs is expected to be good as the obstruction is thought to be intermittent. However, we noted delayed contrast uptake on IVU in 60.6% and differential renal function on EC scan below 40% in 17 patients (56.6%). These indicate the effect of the obstruction on the renal parenchyma and the importance of early detection. Higher association with other anomalies and higher incidence in females has also not been emphasized in the literature so far. We noted associated intrinsic obstruction in 24.24% patients which is highly significant. This category of patients is likely to be missed and inappropriately treated if a "vascular hitch procedure" is performed. None of our patients had postoperative complications. Characteristic features were seen on IVU helping in preoperative diagnosis which can be extrapolated to magnetic resonance urography. There is a higher association of CV in age above 2 years, females, associated congenital anomalies, delayed uptake on IVU and differential renal function below 40% compared to intrinsic obstruction. Associated intrinsic obstruction in 24% with no postoperative complications indicates the superiority of dismembered pyeloplasty over vasculopexy procedures.

Does the histopathologic pattern of the ureteropelvic junction affect the outcome of pyeloplasty.

To investigate the effects of the histopathologic pattern of obstructed ureteropelvic junction (UPJ) specimens, including collagen type 3, elastin, fibrosis and Cajal cells, on the outcome of pyeloplasty. Histopathological specimens obtained following Anderson-Hynes pyeloplasty from 52 patients with intrinsic ureteropelvic junction obstruction (UPJO) between January 2005 and January 2008 were evaluated histopathologically. Patients with extrinsic or secondary UPJO were excluded. Preoperative and postoperative radiographic evaluations were performed either via diuretic renography or intravenous pyelography, or both. Six months post-surgery the patients were divided into 2 groups, as successful surgery (group 1) and unsuccessful surgery (group 2). Histopathological findings (collagen type 3, elastin, fibrosis and Cajal cells) in each group were statistically compared. The study included 52 patients (21 female and 31 male). Mean age of the entire study population was 39.42 ± 14.5 years, versus 39.63 ± 14.9 years in group 1 (n = 47) and 37.4 ± 10.0 years in group 2 (n = 5). Median follow-up was 18 months. There weren't any significant differences in collagen type 3, elastin, fibrosis, or Cajal cells between the 2 groups (P > .05). The histopathologic pattern of UPJ was not a factor associated with the success of pyeloplasty. Based on the present findings, we conclude that surgical technique is more important than the histopathologic pattern of UPJ for the successful treatment of UPJO.

The distribution of interstitial cells of Cajal in congenital ureteropelvic junction obstruction

PurposeThe authors analysed the distribution of c-kit-positive interstitial cells of Cajal (ICCs) in obstructed ureteropelvic junction (UPJ) and its age-related changes.MethodsTwenty specimens were obtained from children with intrinsic ureteropelvic junction obstruction (UPJO), at the average age of 8.1 years (8 months–16.8 years), fixed in formalin and embedded in paraffin. Five control samples were taken from children at the average age of 2.3 years (2.4 months–7.4 years). All specimens were analysed by the immunohistochemistry test with light microscopy with respect to c-kit expression. The distribution of c-kit-positive ICCs in the two groups was compared and the correlation between the distribution of c-kit-positive ICCs and the patients’ age in UPJO cases was analysed. The results were examined by Yates’ χ2 test, Mann–Whitney U test, and t test for Pearson’s correlation coefficient. A P value < 0.05 was considered as statistically significant.ResultsNo statistically significant differences were found in the distribution of c-kit-positive ICCs between UPJO and the control group. No correlation was established between the age of patients with UPJO and the distribution of c-kit-positive ICCs.ConclusionNo distributional difference found in obstructed and unobstructed UPJ seems to indicate that UPJO is not associated with anomalous distribution of c-kit-positive ICCs. Age-related changes in the expression of c-kit-positive ICCs are equally distributed in obstructed UPJ.

Analysis of expression of TNF-alpha and TGF-beta3 in intrinsic ureteropelvic junction obstruction

Ureteropelvic junction (UPJ) obstruction is of critical importance to understand the histopathology of UPJ obstruction in terms of therapy planning and follow-up. For this purpose, our study was conducted with TNF-α and TGF-β markers to investigate possible underlying problems in intrinsic UPJ obstruction. Of the patients who had undergone surgery in our clinic, 36 UPJ segments of patients who had undergone dismembered pyeloplasty surgery due to UPJ obstruction and 14 UPJ segments of the patients who had undergone nephrectomy were collected to form 2 groups. All histological sections were examined by applying immunohistochemical transforming growth factor beta 3 (TGF-β3) and tumour necrosis factor alpha (TNF-α) monoclonal antibody dyes. The mean staining values for TNF-α in mucosal tissue and mucosa were 0.53±0.84 and 0.58±0.84, respectively in the obstruction group, whereas the values observed in the control group were 0.86±0.36 and 0.93±0.47, respectively. While the mean staining values in the obstruction group in mucosal tissue and mucosa for TGF-β3 were 1.75±0.73 and 2.17±0.77, respectively, the values established in the control group were 1.14±0.66 and 1.43±0.93, respectively. The difference between the obstruction and control groups were statistically significant for both values (p<0.05). Only a limited number of studies have been carried out on this particular issue. Data from the present study indicate that TGF-β3 and TNF-α may play a role in the histopathogenesis of UPJ obstruction (Tab. 1, Fig. 1, Ref. 18).

Extracellular Matrix Degradation and Reduced Neural Density in Children With Intrinsic Ureteropelvic Junction Obstruction

To investigate the extracellular matrix microenvironment and nerve supply of ureteropelvic junctions (UPJs) in children with intrinsic UPJ obstruction. Congenital UPJ obstruction is the most common cause of neonatal hydronephrosis. Although many studies investigating the molecular changes within this segment have been performed, the underlying mechanisms of UPJ obstruction are still unclear. Specimens were obtained from 21 children with a mean age of 103.2 months undergoing dismembered pyeloplasty. Control samples included 9 archival specimens from age-matched children without any history of urologic disease. Paraffin-embedded sections were immunostained to detect matrix metalloproteinase 2 (MMP-2), tenascin C (TN-C), and S-100 (for the neuronal supply). Expression patterns were investigated using semiquantitative high-power field magnification analyses, and the MMP-2 and TN-C immunoreactivity were scored. Differences between the 2 groups were examined statistically. All UPJ specimens displayed a resolved muscular coat and replacement of smooth muscle cells by connective tissue. The degree of MMP-2 expression representing matrix turnover was statistically significantly elevated. Similarly, TN-C expression was found to be higher in obstructed specimens. Additionally, the mean S-100 staining was lower than in controls. Although S-100-positive nerve-fibers were more predominant in the adventitia with minimal submucosal and absent intramuscular staining in patient specimens, they were abundant in both adventitia and submucosa with minimal intramuscular staining in the controls. In intrinsic UPJ obstruction samples, a dissolved smooth muscular coat and an overexpression of extracellular matrix proteins, together with depleted nerve supply, was demonstrable.

Integrins expression of smooth muscle cells in ureteropelvic junction obstruction

The ureteropelvic junction obstruction (UPJO) is the most common cause of hydronephrosis. An altered intrinsic malfunction of smooth muscle cells (SMC) is believed to be the underlying mechanism of obstruction. The cytoskeletal structure in SMC in the pathophysiology of UPJO are not intestigated. We have valued the expression of some integrins, talin and β-dystroglycan, that are considered main compound of SMC cytoskeleton. 12 human specimens were obtained during pyeloplasty from children while 6 control specimens were collected during organ explantation. Resected specimens were divided in pelvis, ureteropelvic junction and ureter below the obstruction. An immunofluorescence and a PCR analysis were performed for α7A-, β1A-, α7Band β1D-integrin, talin and β-dystroglycan. Control reactions showed a strong staining of α7Band β1Dintegrin, talin and β-dystroglycan while a weak positivity of α7Aand β1A-integrin was recorded. Differently, in obstructed UPJ talin and β-dystroglycan were slightly impaired, α7Band β1D-integrin were severely reduced and α7Aand β1A-integrin were significantly enhanced. Our observations showed a critical alteration of cytoskeleton and these might justify the altered function and the increased apoptosis in SMC of UPJO. A delayed rearrangement of the cytoscheleton of SMC in UPJO might be linked to a postnatal splicing from α7A and β1A to, respectively, α7Band β1D-integrins. These data perfectly are in accordance with the clinical evidence of a possible post-natal healing of congenital intrinsic UPJO.

Contributions of the Retroperitoneoscopy to the Diagnose of the Ureteropelvic Junction Obstruction in Children: New Surgical Alternatives to Conventional Pyeloplasty

PURPOSE To assess:The correlation between pre and post-retroperitoneoscopy diagnose of the ureteropelvic junction obstruction (UPJO) causes. The impact of Retroperitoneoscopy on the surgical technique used for the resolution of the extrinsic UPJO. MATERIAL AND METHODS Between 2004 and 2006 we have treated 14 patients, with congenital hydronephrosis due to UPJO, by retroperitoneoscopic approach. The mean age of surgery was 22 months (range between 3 months and 12 years). In all patients preoperative study included: ultrasound (US), cystography, diuretic renography and renal scintigraphy; and uro-angio-Magnetic Resonance in 10. Preoperative diagnose was: intrinsic UPJO in 10 patients and extrinsic UPJO due to crossing polar vessels in 4. The mean postoperative follow-up has been 16 months (range between 8 and 20 months). The postoperative outcome has been evaluated by US, renography and renal scintigraphy. RESULTS After -retroperitoneoscopy the diagnose became: intrinsic UPJO in 6, and extrinsic UPJO in 8, due to posterior polar vessel in 2, peri-UPJ fibrosis in 4, and anterior polar vessel in 2. UPJO is due to extrinsic causes in 57% of the patients. These findings resulted in the variation of the surgical technique in 6 patients (42.5%). We performed video-assisted ureteropyeloplasty in 6, pyelopyeloplasty in 2, ureterolysis in 4, and pelvic transposition and pexia in 2. There were no intra - or postoperative complications. The average length of stay was 1,6 days. The postoperative result was improvement of the obstruction in 100%, without differences between those who underwent some kind of plastia from those who did not. CONCLUSIONS Retroperitoneoscopy is an effective method for diagnose and minimally invasive treatment of the ureteropelvic junction obstruction. Retroperitoneoscopy raises new surgical alternatives to ureteropyeloplasty. Surgical technique should be based on Retroperitoneoscopical findings.

HISTOLOGIC DIFFERENCES BETWEEN EXTRINSIC AND INTRINSIC URETEROPELVIC JUNCTION OBSTRUCTION

You have accessJournal of Urology1 Apr 2008HISTOLOGIC DIFFERENCES BETWEEN EXTRINSIC AND INTRINSIC URETEROPELVIC JUNCTION OBSTRUCTION Jenny H Yiee, Sarah Johnson-Welch, Linda A Baker, Warren T Snodgrass, and Duncan T Wilcox Jenny H YieeJenny H Yiee More articles by this author , Sarah Johnson-WelchSarah Johnson-Welch More articles by this author , Linda A BakerLinda A Baker More articles by this author , Warren T SnodgrassWarren T Snodgrass More articles by this author , and Duncan T WilcoxDuncan T Wilcox More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(08)61040-XAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "HISTOLOGIC DIFFERENCES BETWEEN EXTRINSIC AND INTRINSIC URETEROPELVIC JUNCTION OBSTRUCTION." The Journal of Urology, 179(4S), p. 355 © 2008 by American Urological AssociationFiguresReferencesRelatedDetails Volume 179Issue 4SApril 2008Page: 355 Advertisement Copyright & Permissions© 2008 by American Urological AssociationMetricsAuthor Information Jenny H Yiee More articles by this author Sarah Johnson-Welch More articles by this author Linda A Baker More articles by this author Warren T Snodgrass More articles by this author Duncan T Wilcox More articles by this author Expand All Advertisement PDF downloadLoading ...

A New Modification of Dismembered Pyeloplasty for Primary Ureteropelvic Junction Obstruction

Aim: To present the results of a new modification of dismembered pyeloplasty performed to prevent the occurrence of secondary obstruction. Methods: Modified dismembered pyeloplasty was performed in 35 children (age range 3 months to 16 years) who had unilateral ureteropelvic junction obstruction. In postoperative follow-up, presence of hydronephrosis on ultrasonography, differential renal function (DRF) and renal drainage half-time on technetium-99m diethylenetriaminepentaacetic acid (DTPA) renography were recorded and compared with preoperative data. Results: Mean anteroposterior renal pelvic diameter, mean preoperative DRF and radioisotope clearance half-time on DTPA renography of the affected kidneys were 61.4 mm, 38.6% and 34.3 min in children with prenatal hydronephrosis, and 67.5 mm, 37.6% and 39.4 min in children that presented with symptoms, respectively. After surgery, mean anteroposterior renal pelvic diameter, mean DRF and radioisotope clearance half-time on DTPA renography of the affected kidneys were 10.9 mm, 45.9% and 11.9 min in children with prenatal hydronephrosis, and 20 mm, 41.9% and 15.2 min in children that presented with symptoms, respectively. No failure was observed in any patient at an average follow-up of 26 months (range 1–5 years). Conclusions: Open dismembered pyeloplasty is the treatment of choice for intrinsic ureteropelvic junction obstruction. The modification of dismembered pyeloplasty that we performed is an alternative for the prevention of secondary obstruction.

La jonction pyélourétérale chez l’enfant : de la problématique clinique à l’approche morphogénique

The responsibility of the uteropelvic junction (UPJ) syndrome or abnormalities for renal affections and also for high obstructive uropathy is well-known. But, controversies still remain about the anatomic approach of this clinical feature. Our purpose is to elucidate the developmental anatomy of UPJ and eventually to set the steps of the anatomic approach of the UPJ abnormalities. This study also leads to a better understanding of the mechanism of the intrinsic ureteropelvic junction obstructions. A total number of 122 post-mortem specimens with ages ranging from 1 day to 30 months in both sexes underwent formalin treatment for histological investigation. We performed both transverse and longitudinal sections. Hematein-eosin-safran and Masson's trichrome staining were used. Histological examination revealed that myoarchitecture of UPJ set increasingly up. Circular muscle fibers were first to put in. They had an initial arrangement as a ring in neonates and infants. We conclude that circular layer appears first and sooner than others. On the other hand, coincidence in time between ages of our specimens and ages of patients sufferning from UPJ syndrome leads to further investigations to determine the implication of ring-shaped circular layer in intrinsic ureteropelvic junction obstruction.

Altered Expression of Interstitial Cells of Cajal in Congenital Ureteropelvic Junction Obstruction

Peristaltic contractions in the upper urinary tract serve to move urine from the kidney through the ureter to the bladder. Ureteropelvic junction (UPJ) obstruction is the most common cause of congenital hydronephrosis in children. To our knowledge the pathophysiology of UPJ obstruction is unknown. C-kit positive interstitial cells of Cajal (ICCs) are pacemaker cells that facilitate active propagation of electrical events and mediate neurotransmission. We investigated the expression of c-kit positive cells in the muscle layer of normal and obstructed UPJ specimens. A total of 19 human formalin fixed, paraffin embedded specimens of intrinsic UPJ obstruction from children with a mean age of 2.3 years (range 2 months to 12 years) and 7 control samples from children with a mean age of 4.5 years (range 11 months to 9 years) were investigated immunohistochemically for the expression of c-Kit oncoprotein and peripherin by light and laser scanning microscopy. Quantification of immunolabeled structures was quantified using computerized image analysis. Peripherin immunoreactivity was strong in the muscle layer of normal UPJ specimens, while in UPJ obstructed specimens there was a decrease in peripherin positive nerve fibers. In normal UPJ specimens there were many c-Kit positive ICCs between the muscle bundles. The density of ICCs was markedly decreased in the muscle layers of UPJ obstructed specimens. To our knowledge this study shows for the first time the immuno-expression of c-Kit positive ICCs in the proximal part of the normal human upper ureter. The altered density of c-Kit positive cells in UPJ obstruction may have a role in the failure of transmission of peristaltic waves across the UPJ.

Endoscopic and Laparoscopic Treatment of Ureteropelvic Junction Obstruction

Although open pyeloplasty remains the gold standard for treating ureteropelvic junction obstruction, endourology and laparoscopy have revolutionized the management of upper tract stenosis. We present our diagnostic and minimally invasive therapeutic algorithm for the treatment of ureteropelvic junction obstruction. A total of 13 females and 9 males with a mean age of 34.2 years suffering from ureteropelvic junction obstruction were treated with percutaneous endopyelotomy or laparoscopic dismembered pyeloplasty and followed for 47 to 61 months (mean 53.8) and 47 to 62 months (mean 52.5), respectively. Diagnosis was based on findings of ultrasound, excretory urography, furosemide washout renogram and retrograde ureteropyelography. In cases of ureteral kinking color duplex sonography and spiral computerized tomography were performed. In 14 patients with intrinsic stenosis percutaneous endopyelotomy was performed, while the remaining 8 patients (5 with crossing vessels, 2 with an extremely distended pelvis and 1 with a 2.5 cm. stricture) were treated with a laparoscopic dismembered Anderson-Hynes pyeloplasty. In the endopyelotomy group (success rate 92.8%), mean operation time was 1.2 hours, estimated blood loss was 152 ml., unit doses of analgesics were 5.4 tablets, days of hospitalization were 4.2 and time to return to normal activities was 15.7 days. In the laparoscopic group (success rate of 100%) the aforementioned variables were 3.5 hours (p <0.05), 150 ml., 6.3 tablets, 5 and 17.8 days, respectively. Long-term followup excretory urography and/or diuretic renal scan demonstrated improvement in all patients. Percutaneous endopyelotomy should be the treatment of choice for intrinsic ureteropelvic junction obstruction. Laparoscopic dismembered pyeloplasty, although technically challenging, provides excellent results for extrinsic or complicated ureteropelvic junction stenosis.

Structural Changes of Collagen Components and Diminution of Nerves in Congenital Ureteropelvic Junction Obstruction

Purpose Three-dimensional arrangements of smooth muscle cells, collagenous component and peripheral nerves of congenital ureteropelvic junction (UPJ) obstruction were studied in order to clarify the pathogenetic mechanism of interaction among these neuro-myo-stromal components. Materials and Methods The UPJ and upper ureters were obtained from 14 patients with congenital hydronephrosis (7 intrinsic and 4 extrinsic obstruction) and 7 normal controls. Three-dimensional arrangement of each structural component was observed by scanning electron microscopy, and the nerve distribution was analyzed with immunohistochemistry for protein gene product 9.5. Results The UPJ of intrinsic obstruction had structural features as follows. Muscle fascicles were sparse and thin. Each muscle cell was thin in diameter. Intercellular spaces were six to seven times wider than controls. Collagen fibrillar sheaths of smooth muscle cells (pericellular collagen fibrils attached to the basement membrane) were interwoven to form a dense felt-like structure against thin lace-like sheaths in controls. Interstitial collagenous component showed dense and compact structure against loose network of wavy collagen bundles in controls. In the muscular layer, nerve distribution was decreased to about one-third of controls. In contrast, non-stenotic portion of intrinsic UPJ obstruction as well as materials from extrinsic UPJ obstruction showed no structural difference as compared with controls. Conclusions In the intrinsic obstruction, nerve fibers were depleted in the muscular layers in the ureteric walls, resulting in dysfunction and atrophy of muscle fibers and an increase of collagen fibers in the muscle layers with abnormal accumulation of intercellular and interstitial collagen. These changes may disrupt the mobility of UPJ and lead to both mechanical and functional obstruction.

Pathophysiology of Ureteropelvic Junction Obstruction: Experimental and Clinical Observations

We compared experimental ligature-induced ureteropelvic junction obstruction in the dog with naturally occurring ureteropelvic junction obstruction in children to determine if clinical behavior and difficulties in diagnosis could be related to different types or components of obstruction at the ureteropelvic junction. Measurements of flow rate out of the ligature-obstructed canine renal pelvis demonstrated a pressure-dependent pattern in which flow increased linearly in response to increasing pressures. In 5 human kidneys with intrinsic ureteropelvic junction obstruction a similar pressure-dependent pattern was demonstrated. This was in contrast to 6 human kidneys with extrinsic mechanical ureteropelvic junction obstruction in which a volume-dependent pressure flow pattern occurred, such that urinary flow rate did not keep pace with increases in pelvic pressure. In some cases flow actually decreased at high pressures because the ureteropelvic junction became self-obstructing as the pelvis enlarged.These findings indicate that the precise pathological anatomy of the ureteropelvic junction defines the pattern of flow across the obstruction. The 2 different types of obstruction, pressure-dependent and volume-dependent flow restrictions, which exist are important determinants of the clinical behavior of the obstructed kidney insofar as its potential for progressive hydronephrosis. They also help to explain why diagnostic tests for assessing obstruction in hydronephrosis are inaccurate at times.