Angiotensin converting enzyme inhibition worsens the excretory phase of diuretic renography for obstructive hydronephrosis.

PURPOSE: A growing body of evidence identifies the renin-angiotensin system as a key factor in the onset and progression of renal damage in chronic partial obstruction, which often represents a complex diagnostic challenge. A prospective study was undertaken to evaluate the role of captopril mercaptoacetyltriglycine-3 (MAG-3) renography as an early diagnostic test of obstruction. We report the results in a subgroup of children who underwent surgical correction for pyeloureteral obstruction. MATERIALS AND METHODS: Pyeloplasty was performed in 12 patients, including 10 males, 2 to 72 months old (median age 7) with unilateral hydronephrosis, including normal renal function and blood pressure. Basal and captopril enhanced diuretic renography with 99mtechnetium MAG-3 was performed within 24 hours using the same hydration and diuretic stimulus (0.75 mg./kg. furosemide), and 0.75 mg./kg. captopril was administered orally 60 to 90 minutes before scintigraphy. RESULTS: No adverse effects or modifications of the blood pressure were observed after captopril administration. The diuretic response was deeply worsened by angiotensin converting enzyme inhibition in each hydronephrotic kidney even when the basal study was only slightly abnormal (15-minute washout basal -27 +/- 16%, after captopril -9 +/- 13, p <0.005). After surgical correction the diuretic washout during angiotensin inhibition appeared normal in all patients (15-minute washout -56 +/- 14%). Separate renal function and parenchymal transit of MAG-3 were not modified by angiotensin converting enzyme inhibition, preoperatively or postoperatively. CONCLUSIONS: Our data confirm the influence of angiotensin on the kidney excretory system in human hydronephrosis and suggest a role for captopril enhanced diuretic renography in the early diagnosis of pyeloureteral obstruction. Further work is needed to evaluate angiotensin converting enzyme inhibition as a protective agent in obstructive nephropathy.

Long-term followup of endoscopic incision of ureteroceles: intravesical versus extravesical.

PURPOSE: Endoscopic incision was performed as the initial therapy for ureteroceles in children presenting to our institutions between 1985 and 1990. To assess the long-term efficacy of this treatment modality we reevaluated the outcome of these patients. MATERIALS AND METHODS: Parameters reviewed included patient age at surgery, position of the ureterocele, a duplex system, preoperative and postoperative reflux, and the need for additional operations. Statistical analysis consisted of chi-square and Wilcoxon's rank sum tests. RESULTS: Of the patients 22 had intravesical and 22 had extravesical ureteroceles. Average age at initial surgery was 1.9 +/- 3.7 years with average followup of 7.2 +/- 3.1 years. A second operation was required in 18 cases (41%), which was significantly more likely for an extravesical ureterocele (18% versus 64%, p = 0. 002), a duplex system (p = 0.026) or preoperative reflux (p = 0.02). Second operations included reimplantation in 13 cases, upper pole partial nephrectomy in 7, total nephroureterectomy in 3, bladder neck reconstruction in 3 and lower pole pyeloplasty in 3. The only secondary operations performed for intravesical ureteroceles were reimplantation in 3 cases and upper pole nephrectomy in 1. New onset reflux developed in 14 of 27 patients (52%) postoperatively, including 7 with intravesical and 7 with extravesical ureteroceles. None required a second open operation. CONCLUSIONS: With extended followup the percentage of patients requiring open surgery after endoscopic incision of ureteroceles increased from our original report of 27% to 41% (p = 0.166). Only 18% of cases with an intravesical ureterocele required a subsequent operation compared to 64% with an extravesical ureterocele (p = 0.002). The reduction in size of the obstructed ureter following endoscopic decompression facilitated successful reimplantation. Endoscopic puncture permits definitive treatment in the majority of children by at most a single incision, open operation at the bladder level.

Renal glomerular response to the inhibition of prostaglandin E2 synthesis and protein loading after the relief of unilateral ureteropelvic junction obstruction.

PURPOSE: We investigated glomerular filtration rate and renal function reserve after the surgical relief of partial obstruction. MATERIALS AND METHODS: We evaluated 4 boys and 1 girl 9 to 14 years old who underwent pyeloplasty because of unilateral ureteropelvic junction obstruction. Contralateral normal kidneys served as controls. The glomerular filtration rate (inulin clearance), and urinary excretion of prostaglandin E2, thromboxane B2 and endothelin were determined at baseline and after a meal of 4 gm./kg. cooked unsalted red meat on day 4 postoperatively. Tests were repeated the following day 1 hour after the oral administration of 20 mg./kg. aspirin, an inhibitor of prostaglandin E2 synthesis. Urine was collected separately through a bladder catheter and another catheter placed in the upper renal pelvis at surgery. RESULTS: Glomerular filtration rate at baseline was significantly greater in normal than in surgically treated kidneys (77.2 ml. per minute, range 60 to 98 versus 63.6, range 43 to 78, p = 0.04). Aspirin did not change baseline inulin clearance in normal kidneys but it significantly decreased the glomerular filtration rate in operated renal units (-4% versus -26.4%, p = 0.04). The concentration of all vasoactive compounds was not significantly different in the urine specimens of normal and operated kidneys. The administration of aspirin resulted in a significant decrease in mean urinary prostaglandin E2 excretion plus or minus standard error in operated but not in normal renal units (0.64+/-0.12 ng. per minute versus 0.27+/-0.06, p = 0.04). When expressed as mean versus baseline values, protein induced glomerular hyperfiltration seemed lower in operated than in contralateral intact kidneys (6.9% and 12.4%, respectively). CONCLUSIONS: In the immediate postoperative period previously obstructed kidneys maintain renal function via mechanisms that depend on the activation of prostaglandin, mimicking normal renal function. This effect is decreased by drugs that inhibit prostaglandin E2 production. Therefore, renal damage may be present when the glomerular filtration rate appears normal.

Guiding spontaneous tissue regeneration for urethral reconstruction: long-term studies in the rabbit.

We designed long-term in vivo experiments to study rabbit urethral regeneration and remodelling over a hyaluronan biodegradable prosthesis. Seven months after the resection of a 1.5-cm-long tract of the urethra and its substitution with the prosthesis, radiological analysis showed the disappearance of the implant and the re-establishment of urethral continuity along the transmural defect. The regenerated tissue remodelled around the implant and exhibited good distensibility under pressure. Histological evaluation showed that the neo-urethra was lined with transitional epithelium and the stroma contained abundant elastic fibres. An examination of the pattern of the major cytoskeletal and cytocontractile proteins of smooth muscle cells and fibroblasts was able to distinguish fibroblasts from smooth muscle cells and myofibroblasts in the neo-urethra. These experiments provide evidence for the potential, successful use of biocompatible/bioresorbable devices for reconstructive surgery of the urethra.

Time-dependent remodeling of the bladder wall in growing rabbits after partial outlet obstruction.

PURPOSE: We asked whether a urethral constriction gradually developed during growth would give rise to a structural remodeling of the bladder wall distinct from that of the mature rabbits in terms of cellular response. MATERIALS AND METHODS: We examined the serosa and detrusor muscle in immature rabbits whose urethra was obstructed at 30 days postnatal and studied 7 to 30 days after partial outlet obstruction. Morphometry, bromo-deoxyuridine (BrdU) incorporation, Western blotting and immunocytochemical staining with a panel of monoclonal antibodies specific to selected cytoskeletal, cytocontractile and membrane-related proteins unique to non-muscle and smooth muscle cells (SMC) were used to analyze the effects of obstruction on the differentiation pattern. RESULTS: In comparison with results in adult obstructed bladders, we have found that in growing rabbits: (1) the cell conversion from fibroblasts to SMC, occurring within the 'extrinsic' region of serosal thickening, takes place earlier; (2) newly formed SMC are localized exclusively to the thickened serosa, and can group in bundles depending on the density of the regional innervation; (3) the peak level of BrdU incorporation is more elevated than in the adult bladder wall; and (4) change in the phenotypic profile of SMC of detrusor muscle is delayed. CONCLUSION: These data indicate that the basic features of structural remodeling in the two models are similar, though partial outlet obstruction produced in growing animals accelerates the fibroblast conversion to SMC and their spatial, differentiation-specific arrangement in the serosa. The late phenotypic changes in obstructed detrusor muscle correlate with the decline of the DNA synthesis level after an initial burst and strongly suggest that newly formed SMC in the serosa do not derive from pre-existing SMC.

[Chronic renal failure secondary to vesicoureteral reflux: is the prevention possible?]. / Insufficienza renale cronica secondaria a reflusso vescico-ureterale: è possibile la prevenzione?

Vesicoureteral reflux (VUR) is the commonest cause of end-stage renal failure reported by the ITALKID (Italian Register of Chronic Renal Failure) (CRF) in children (0-15 years). Herein we report 131 children (53 M and 78 F) with a diagnosis of VUR made in our Centre between 1987 and 1994. Diagnosis was made in 69% of cases (85/131) during the 1st year of life and in 31% of cases (47/131) afterwards. VUR was demonstrated following a prenatal ultrasonography suspicion in 24/131 and after symptoms such as urinary tract infection (94/131) and poor growth (6/131). 75/131 of patients were treated conservatively (continuous chemoprophylaxis) while 56/131 underwent an antireflux surgery. CRF was found in 14% (19/131) of cases even though the diagnosis of VUR was performed in most of the cases (79%) during the 1st year of life. In conclusion prenatal ultrasonography has a low sensibility in the diagnosis of VUR. In addition, an early diagnosis made during the 1st year of life do not prevent CRF. The study was carried out in a Centre where patients with urological problems are referred from a large part of Northern East of Italy and this may explain the high prevalence of CRF and of children receiving a surgical treatment.

Reconstructive surgery of the urethra: a pilot study in the rabbit on the use of hyaluronan benzyl ester (Hyaff-11) biodegradable grafts.

We investigated the outcome of reconstructive surgery of the urethra through guides composed of a novel biodegradable and highly biocompatible polymer, Hyaff-11. A tract of about 1.5 cm of the rabbit pendulous urethra was totally resected and replaced by a Hyaff-11 tubular graft. Eleven animals were analysed at each of the time points ranging from 7 days to 4 weeks following surgery. Histological and radiological evaluation showed a satisfactory remodelling of the neo-urethra around the implant. The regenerated connective tissue connected both urethral stumps within the first 7 days. On postoperative week 3, the Hyaff-11 guide had disappeared. At the 4-week time point the retrograde urethrogram showed a good distensibility of the neourethra. The regenerated stroma consisted of fibroblastic cells, and collagenous and elastic fibres. The neo-epithelium was pluristratified and exhibited cells of the cuboidal type.

[Diagnostic and therapeutic protocol in malformative uropathies prenatally diagnosed]. / Protocollo diagnostico e terapeutico delle uropatie malformative con diagnosi prenatale.

The increased frequency of prenatal detection of urinary tract abnormalities has brought to the attention of the pediatrician a high number of neonates and infants with asymptomatic hydronephrosis, which represents the most common form of uropathy. As it becomes clear that hydronephrosis does not necessarily mean obstruction, the purpose of the evaluation is to identify those infants in whom hydronephrosis will cause progressive renal deterioration, because of an ongoing restriction to urinary outflow. In the present paper, the discussion of the post-natal diagnosis and management focuses on the embryologic background, the pathophysiology of the obstruction and the rationale to utilise the different diagnostic techniques (ultrasonography, associated with the use of the Doppler; intravenous urography; avoiding cystourethrography; renal scintigraphy).

Proliferation of submesothelial mesenchymal cells during early phase of serosal thickening in the rabbit bladder is accompanied by transient keratin 18 expression.

Partial outlet obstruction of the rabbit bladder induces serosal thickening and smooth muscle (SM) hypertrophy. Within thickened serosa, submesothelial (mesenchymal) cells differentiate into SM cells after 30 days of obstruction[S. Buoro et al. Lab. Invest. 69, 589-602, 1993]. Here, we show that submesothelial cells transiently express keratin (K) 18 but not K8 soon after obstruction. We investigated a possible relationship between keratin expression and cell proliferation/differentiation in vivo and in vitro. The results of this study indicate that expression of K18 is spatiotemporally related to the pattern of cell proliferation with respect to the localization of an elastic membrane which divides the thickened serosa into an "extrinsic" and an "intrinsic" region. Moreover, K18 is not present in bladder mesenchyma during early development, indicating that its expression in the adult is not attributable to a dedifferentiation process. However, simultaneous K18, K8, and desmoplakin (DP) expression can be induced in normal and thickened serosa upon treatment with bromo-deoxyuridine. Our results indicate that K18 is a marker of proliferating mesenchymal cells in rabbit serosa, whereas the combined expression of K18, K8, and DP might be related to the hypothesized alterations in the stability of gene expression. A model is proposed in which keratin-containing submesothelial cells can act as a "transit" cell phenotype involved in both regenerating mesothelial cells and formation of SM cells.

Bellini duct carcinoma. A clinical and in vitro study.

OBJECTIVE: Bellini duct carcinoma (BDC) is a rare and highly aggressive renal tumor whose histogenesis is still a matter of debate although a putative origin from collecting ducts has been proposed. METHODS: A primary tumor cell culture was obtained from a BDC of a 57-year-old man who presented with a mass of the right kidney. The patient died from disease progression 18 months after diagnosis. The light and ultrastructural features were consistent with previous reports on BDC. The expression of low (Ker 18) and high (Ker 5, Ker 8, Ker 10) molecular weight keratins was studied. RESULTS: The BDC tumor cells displayed strong positivity for keratins, 5, 8 and 18 but did not react with the anti-keratin 10 antibody. Northern blot analysis of total mRNA revealed expression of the c-erbB-1 oncogene unlike two conventional clear cell carcinomas of the kidney used as control. Cytogenetic analysis revealed an aneuploid karyotype: 53,XY,del(1)(p34),+iso(1q),+iso(5p),+4,+7,+8,-14,del(16)(q22). No submicroscopic deletion on p14-21 and p26 regions of the short arm of chromosome 3 was detected on Southern blot analysis. CONCLUSIONS: The absence of structural changes in the short arm of chromosome 3 (usually present in hereditary and sporadic renal cell carcinomas) in the presence of chromosomal abnormalities observed in malignant lesions of urothelial origin confers to BDC a unique genetic profile among papillary tumors of the kidney.

Contractility and phenotype transitions in serosal thickening of obstructed rabbit bladder.

Partial outlet obstruction of rabbit bladder induces serosal thickening and smooth muscle (SM) cell hypertrophy that are accompanied by phenotypic changes in the expression of cytoskeletal and cytocontractile proteins. In the present study, we compare the observed progressive phenotypic changes with the contractile responses of strips of the thickened serosa. At 15 days after partial outlet obstruction, although cells in thickened serosa demonstrate the presence of nonmuscle (NM) myosin of A-like type, vimentin, and SM alpha-actin, no contractile responses of this tissue were noted. At later times (30 days), this tissue expressed in addition SM myosin, and this pattern was paralleled by the development of KCl-stimulated contractility. It is only after 60 days that the serosa demonstrated the expression of desmin, phosphoglucomutase (PGM)-related protein, and was locally negative for NM myosin, indicating a maturation toward adult SM cells. Concomitant to this phenotypic change, the response to KCl increased, and a bethanechol-stimulated contractile response developed. At no time period did the serosal layer react with anti-synaptophysin or anti-neurofilament proteins nor did the strips respond to field stimulation (via release of neurotransmitters), showing that SM cell differentiation and development of contractile responses during serosal thickening are independent of innervation.

[Reconstructive surgery in complex hypospadias: therapeutic indications and technical considerations in 93 cases]. / La cirugía reconstructiva de los hipospadias complejos: indicaciones terapéuticas y consideraciones técnicas en 93 casos.

Perineo-scrotal hypospadias and the severe sequelae of a failed repair procedure are complicated cases. The present study describes our experience in the treatment of complex hypospadias, the new therapeutic possibilities, their indications and results. From 1981 to 1992, 93 children with complex hypospadias underwent surgery (53 underwent surgery for the first time and 40 for severe sequelae of a failed procedure). Excellent cosmetic results were achieved by surgery. For those undergoing hypospadias repair for the first time, we used a pedicled preputial flap following the Duckett (12 cases) or Standoli (41 cases) technique. For those with severe sequelae from a failed procedure, we utilized a pedicled skin flap (18 cases) or free flap of bladder mucosa or penile skin (22 cases). The overall complication rate was 50% (47 patients). Surgical repair of complex hypospadias is a relatively long and complicated procedure with a long learning curve and a high complication rate in the initial phase. Fistula is the most common complication, although closure is very simple due to the abundant, well vascularized, healthy tissue. Overall our results have been satisfactory, considering the severity of these cases.

Technical options in complex ureteral lesions: 'ureter-sparing' surgery.

From January 1979 to December 1992, 74 patients with ureteral lesions due to ureteral or renal instrumentations, failed gynecological or reconstructive surgery were addressed to our department for a reconstructive program. Fifty-two of them were managed by standard ureteropyeloanastomosis or psoas bladder hitch and ureteral reimplants. Twenty-two patients (12 females, 10 males, age range 28-68 years) suffered from extensive ureteral lesions (5-7 cm) and were managed by major ureteral reconstructive surgery intended to restore urothelial continuity. Three patients had a solitary kidney, and 6 cases suffered from bilateral ureteral injuries. The procedures employed were: psoas kidney hitch with ureteropelvic anastomosis (4 cases), kidney psoas bladder hitch (5 cases), 'extended' psoas bladder hitch (5 cases), transureterouretero-anastomosis+psoas bladder hitch (5 cases), psoas kidney-bladder hitch and transureterouretero-anastomosis (1 case), renal autotransplantation (2 cases). Only 5 minor postoperative complications were observed and all patients but one had satisfactory results with a follow-up ranging from 6 to 84 months. The authors believe that the restoration of urothelial continuity is the best option compared to other technical solutions such as ileal replacement, or diversion and nephrectomy. Autotransplantation should be reserved for rare selected cases.

Unusual, benign asymptomatic scrotal masses in children: case reports and review of the literature.

Asymptomatic scrotal masses (ASM) in children constitute an entity of pathologies, ranging from congenital anomalies to neoplasms. Testicular ultrasound is the imaging modality of choice in the evaluation of ASM, although there is extensive overlap between benign and malignant lesions. Five children with ASM of benign origin are presented: 2 boys had extratesticular mass (one paratesticular lipoma and one voluminous sebaceous scrotal cyst); the remaining 3 patients had testicular mass (one supernumerary testis, one intratesticular cyst and one unilateral testicular hypertrophy). Basing on the ultrasonographic appearance, a certain diagnosis of benign lesion was made only in the last 2 cases; the remaining patients underwent explorative inguinotomy in order to rule out any malignancy. Some guidelines for proper diagnosis of ASM in childhood are proposed by the authors. However, at least in children, testicular preservation should not be based only on the sonographic findings, and surgical exploration is mandatory whenever the nature of the lesion remains unclear.

Myofibroblast-derived smooth muscle cells during remodelling of rabbit urinary bladder wall induced by partial outflow obstruction.

BACKGROUND: Fibrosis of serosa, along with smooth muscle (SM) cell hypertrophy, has been shown to occur in the rabbit bladder after partial outflow obstruction. Identification of cells involved in the serosal thickening can be of primary interest to elucidate the functional changes that this organ undergoes. EXPERIMENTAL DESIGN: Cytoskeletal protein composition of cells present in the thickened serosa at different times from the onset of obstruction (7, 15, 30 and 60 days) was evaluated. This was accomplished by means of a panel of monoclonal antibodies specific for a number of differentiation markers of mesenchymal cells (vimentin, desmin, alpha-actin of SM type, nonmuscle (NM) and SM myosins), and by immunocytochemical and immunochemical techniques. RESULTS: The immunocytochemical study revealed that cells in serosal thickening follow a two-step maturation process from pre-existing vimentin-positive cells. In the first time period (7 to 15 days of obstruction), these cells predominantly achieved an immunophenotype corresponding to that of a specific myofibroblast subtype (i.e., containing vimentin, NM myosin, and SM alpha-actin). After 30 days from the onset of obstruction, the cytoskeletal protein content of serosal cells, as also revealed by Western blotting experiments, shifted towards that of fetal-type SM cells (i.e., presence of vimentin, NM myosin, SM alpha-actin, and SM myosin isoforms). Distribution of vimentin, desmin, SM alpha-actin, and SM myosin in tissue culture as well as the ultrastructure in vivo very closely resembled that of SM cells. Bromodeoxyuridine incorporation studies indicated that cells accumulated in the serosa of obstructed bladders did not derive, at least initially, from SM cells of the detrusor muscle. CONCLUSIONS: These findings are consistent with the existence of a differentiation process in which resident mesenchymal cells of bladder serosa may transform to myofibroblasts and, subsequently, in fetal-type SM cells during experimental outflow obstruction.

Cytoskeletal and cytocontractile protein composition of smooth muscle cells in developing and obstructed rabbit bladder.

The differentiation patterns of smooth muscle cells (SMC) in rabbit bladder during development and in the hypertrophic response to partial outflow obstruction induced in adult animals were evaluated by biochemical and immunochemical techniques and by using a panel of monoclonal antibodies specific for desmin, vimentin, alpha-actin of smooth muscle (SM) type, SM myosin, and nonmuscle (NM) myosin isoforms. Desmin and SM alpha-actin were homogeneously distributed in SMC of developing, adult, and obstructed bladders. Conversely, marked changes in the ratio and antigenicity of SM myosin isoforms were observed by SDS electrophoresis and Western blotting, respectively. In particular, the 205 K (SM1) isoform was down-regulated with development whereas the 200 K (SM2) isoform was up-regulated around 7 days after birth and down-regulated in the obstructed bladder. Vimentin was expressed in SMC of the fetal bladder and declined markedly during postnatal, physiological hypertrophy of SMC, which occurs concomitantly with diminution of DNA synthesis. This polypeptide became detectable, however, in SMC of obstructed bladders. The 196 K (NM) myosin isoform recognized by NM-A9 antibody, present only in endothelium of blood vessels and in mucosa of normal fetal and adult bladders, became expressed in detrusor muscle, when SMC underwent a process of pathological hypertrophy. The reexpression of vimentin and the de novo appearance of NM myosin isoform in hypertrophic bladders can be reversed when the tissue mass is reduced, such as in bladders after 1-month recovery from partial obstruction. Thus, a specific NM myosin isoform can be used as a marker of SMC hypertrophy in obstructed bladder. In addition, the combined use of anti-vimentin and NM-A9 antibodies can distinguish between SMC which are in the physiological or in the pathological condition of adaptive bladder hypertrophy.

Endoscopic incision of ureteroceles: intravesical versus ectopic.

A total of 51 children, mostly less than 2 years old, underwent endoscopic incision of ureteroceles as a primary form of treatment. In 73% no further surgery was required. Of the patients 19 were diagnosed by prenatal ultrasound, with a urinary tract infection the usual presenting symptom in the remainder. Of 27 intravesical cases endoscopic incision resulted in decompression of the ureterocele in 93%, with preservation of upper pole function in 96%, and secondary surgical procedures were required in 7%. Reflux was created in 18% and it persisted in 2 of 4 patients. Of 24 cases of ectopic (extravesical) ureteroceles incision resulted in decompression in 75%, with upper pole function preserved in 50%. Reflux was created in 47% and a secondary surgical procedure was performed in 50%. Preservation of upper pole function was significantly better for intravesical versus ectopic ureteroceles (p < 0.01), and the requirement for secondary surgical procedure was greater with ectopic ureteroceles (p < 0.01). Three patients had intermittent bladder outlet obstruction following the incision and required further surgery. The 2 different techniques for incision of intravesical and ectopic ureteroceles are described. The role of endoscopic incision in the overall management of ureteroceles is confirmed by this review, and the need for partial nephroureterectomy may diminish.

Ectopia of the vas deferens into the ureter. Case report and review of the literature.

Ectopia of the vas deferens into the ureter is a rare occurrence, frequently associated with anorectal anomalies. To date, 20 cases have been reported, accounting for a total of 26 vasoureteral communications, 6 of which are bilateral. Embryologically, ureteral ectopia of the vas deferens may be explained by an underlying defect in the proximal mesonephric duct or an abnormally cranial origin of the ureteric bud. We add the case of a newborn with an ectopic vas terminating into the ureter of a multicystic kidney.