Preliminary report: Surgical outcomes following genitoplasty in children with moderate to severe genital atypia.

INTRODUCTION: Prior studies of outcomes following genitoplasty have reported high rates of surgical complications among children with atypical genitalia. Few studies have prospectively assessed outcomes after contemporary surgical approaches. OBJECTIVE: The current study reported the occurrence of early postoperative complications and of cosmetic outcomes (as rated by surgeons and parents) at 12 months following contemporary genitoplasty procedures in children born with atypical genitalia. STUDY DESIGN: This 11-site, prospective study included children aged ≤2 years, with Prader 3-5 or Quigley 3-6 external genitalia, with no prior genitoplasty and non-urogenital malformations at the time of enrollment. Genital appearance was rated on a 4-point Likert scale. Paired t-tests evaluated differences in cosmesis ratings. RESULTS: Out of 27 children, 10 were 46,XY patients with the following diagnoses: gonadal dysgenesis, PAIS or testosterone biosynthetic defect, severe hypospadias and microphallus, who were reared male. Sixteen 46,XX congenital adrenal hyperplasia patients were reared female and one child with sex chromosome mosaicism was reared male. Eleven children had masculinizing genitoplasty for penoscrotal or perineal hypospadias (one-stage, three; two-stage, eight). Among one-stage surgeries, one child had meatal stenosis (minor) and one developed both urinary retention (minor) and urethrocutaneous fistula (major) (Summary Figure). Among two-stage surgeries, three children developed a major complication: penoscrotal fistula, glans dehiscence or urethral dehiscence. Among 16 children who had feminizing genitoplasty, vaginoplasty was performed in all, clitoroplasty in nine, external genitoplasty in 13, urethroplasty in four, perineoplasty in five, and total urogenital sinus mobilization in two. Two children had minor complications: one had a UTI, and one had both a mucosal skin tag and vaginal mucosal polyp. Two additional children developed a major complication: vaginal stenosis. Cosmesis scores revealed sustained improvements from 6 months post-genitoplasty, as previously reported, with all scores reported as good or satisfied. DISCUSSION: In these preliminary data from a multi-site, observational study, parents and surgeons were equally satisfied with the cosmetic outcomes 12 months after genitoplasty. A small number of patients had major complications in both feminizing and masculinizing surgeries; two-stage hypospadias repair had the most major complications. Long-term follow-up of patients at post-puberty will provide a better assessment of outcomes in this population. CONCLUSION: In this cohort of children with moderate to severe atypical genitalia, preliminary data on both surgical and cosmetic outcomes were presented. Findings from this study, and from following these children in long-term studies, will help guide practitioners in their discussions with families about surgical management.

Prospective assessment of cosmesis before and after genital surgery.

INTRODUCTION: Little data exist about the surgical interventions taking place for children with disorders of sex development (DSD). Most studies that have evaluated cosmetic outcomes after genitoplasty have included retrospective ratings by a physician at a single center. OBJECTIVE: The present study aimed to: 1) describe frequency of sex assignment, and types of surgery performed in a cohort of patients with moderate-to-severe genital ambiguity; and 2) prospectively determine cosmesis ratings by parents and surgeons before and after genital surgery. STUDY DESIGN: This prospective, observational study included children aged <2 years of age, with no prior genitoplasty at the time of enrollment, moderate-to-severe genital atypia, and being treated at one of 11 children's hospitals in the United States of America (USA). Clinical information was collected, including type of surgery performed. Parents and the local pediatric urologist rated the cosmetic appearance of the child's genitalia prior to and 6 months after genitoplasty. RESULTS: Of the 37 children meeting eligibility criteria, 20 (54%) had a 46,XX karyotype, 15 (40%) had a 46,XY karyotype, and two (5%) had sex chromosome mosaicism. The most common diagnosis overall was congenital adrenal hyperplasia (54%). Thirty-five children had surgery; 21 received feminizing genitoplasty, and 14 had masculinizing genitoplasty. Two families decided against surgery. At baseline, 22 mothers (63%), 14 fathers (48%), and 35 surgeons (100%) stated that they were dissatisfied or very dissatisfied with the appearance of the child's genitalia. Surgeons rated the appearance of the genitalia significantly worse than mothers (P < 0.001) and fathers (P ≤ 0.001) at baseline. At the 6-month postoperative visit, cosmesis ratings improved significantly for all groups (P < 0.001 for all groups). Thirty-two mothers (94%), 26 fathers (92%), and 31 surgeons (88%) reported either a good outcome, or they were satisfied (see Summary Figure); there were no significant between-group differences in ratings. DISCUSSION: This multicenter, observational study showed surgical interventions being performed at DSD centers in the USA. While parent and surgeon ratings were discordant pre-operatively, they were generally concordant postoperatively. Satisfaction with postoperative cosmesis does not necessarily equate with satisfaction with the functional outcome later in life. CONCLUSION: In this cohort of children with genital atypia, the majority had surgery. Parents and surgeons all rated the appearance of the genitalia unfavorably before surgery, with surgeons giving worse ratings than parents. Cosmesis ratings improved significantly after surgery, with no between-group differences.

The Value of PIC Cystography in Detecting De Novo and Residual Vesicoureteral Reflux after Dextranomer/Hyaluronic Acid Copolymer Injection.

The endoscopic injection of Dx/HA in the management of vesicoureteral reflux (VUR) has become an accepted alternative to open surgery. In the current study we evaluated the value of cystography to detect de novo contralateral VUR in unilateral cases of VUR at the time of Dx/HA injection and correlated the findings of immediate post-Dx/HA injection cystography during the same anesthesia to 2-month postoperative VCUG to evaluate its ability to predict successful surgical outcomes. The current study aimed to evaluate whether an intraoperatively performed cystogram could replace postoperative studies. But a negative intraoperative cystogram correlates with the postoperative study in only 80%. Considering the 75-80% success rate of Dx/HA implantation, the addition of intraoperative cystograms cannot replace postoperative studies. In patients treated with unilateral VUR, PIC cystography can detect occult VUR and prevent postoperative contralateral new onset of VUR.

Monoclonal antibodies to guinea pig interferon-gamma: tools for cytokine detection and neutralization.

We have generated polyclonal antisera and monoclonal antibodies against recombinant guinea pig IFN-gamma. These antibodies were used to inhibit the function of IFN-gamma in vitro and to establish a capture ELISA system for the detection and quantitation of this cytokine. Although recombinant protein expressed in E. coli was available in abundance, it was only of limited value to develop a capture ELISA which detects the native cytokine, since only a limited number of monoclonal antibodies reacted both with the recombinant and the native protein. Positive test results in an initial ELISA setup with recombinant IFN-gamma were not predictive for the detection of IFN-gamma from activated T-lymphocytes in the same assay. After evaluating several different combinations of rabbit antisera and monoclonal antibodies, an assay system was established which uses two mouse monoclonal antibodies as capture and detecting reagents. Three of the monoclonal antibodies and the rabbit antisera were able to block the function of guinea pig IFN-gamma when assayed in a luciferase reporter assay.

The common ileal ureter: a new technique for compliant ureterocystoplasty.

PURPOSE: Ureterocystoplasty is an effective technique for bladder reconstruction in patients with megaureter. Initial reports were encouraging but later repeat augmentation with bowel was necessary in many patients. We evaluated whether repeat augmentation after ureterocystoplasty could be avoided using two-thirds of each megaureter. MATERIALS AND METHODS: Ureterocystoplasty was performed in 6 patients using the distal two-thirds of the 2 ureters. Continuity was reestablished by anastomosis of the remaining proximal ureters to a tubularized and tapered piece of ileum, which was reimplanted in an antireflux manner into the reconstructed bladder. All patients underwent preoperative and postoperative evaluation with ultrasound, creatinine, voiding cystourethrogram, nuclear renal scan and videourodynamic testing. RESULTS: Patient age at ureterocystoplasty was between 7 and 15 years with a median followup of 45.3 months. Preoperative videourodynamics demonstrated low capacity bladders with grade 5 vesicoureteral reflux and a poor mean bladder compliance of 7.4 ml/cm H2O. Bladder capacity increased up to 12-fold postoperatively with a mean compliance rate of 58 ml/cm H2O and vesicoureteral reflux resolved in all patients. One patient required endoscopic incision of the reimplanted common ileal ureter but no other complications occurred. CONCLUSIONS: The common ileal ureter provided a long-term compliant reservoir without the need for future repeat augmentation in all patients. Using standard urological techniques the complication rates remained low and recovery time was similar to that of standard ureterocystoplasty.

Increased expression of type 2 3alpha-hydroxysteroid dehydrogenase/type 5 17beta-hydroxysteroid dehydrogenase (AKR1C3) and its relationship with androgen receptor in prostate carcinoma.

Type 2 3alpha-hydroxysteroid dehydrogenase (3alpha-HSD) is a multi-functional enzyme that possesses 3alpha-, 17beta- and 20alpha-HSD, as well as prostaglandin (PG) F synthase activities and catalyzes androgen, estrogen, progestin and PG metabolism. Type 2 3alpha-HSD was cloned from human prostate, is a member of the aldo-keto reductase (AKR) superfamily and was named AKR1C3. In androgen target tissues such as the prostate, AKR1C3 catalyzes the conversion of Delta(4)-androstene-3,17-dione to testosterone, 5alpha-dihydrotestosterone to 5alpha-androstane-3alpha,17beta-diol (3alpha-diol), and 3alpha-diol to androsterone. Thus AKR1C3 may regulate the balance of androgens and hence trans-activation of the androgen receptor in these tissues. Tissue distribution studies indicate that AKR1C3 transcripts are highly expressed in human prostate. To measure AKR1C3 protein expression and its distribution in the prostate, we raised a monoclonal antibody specifically recognizing AKR1C3. This antibody allowed us to distinguish AKR1C3 from other AKR1C family members in human tissues. Immunoblot analysis showed that this monoclonal antibody binds to one species of protein in primary cultures of prostate epithelial cells and in LNCaP prostate cancer cells. Immunohistochemistry with this antibody on human prostate detected strong nuclear immunoreactivity in normal stromal and smooth muscle cells, perineurial cells, urothelial (transitional) cells, and endothelial cells. Normal prostate epithelial cells were only faintly immunoreactive or negative. Positive immunoreactivity was demonstrated in primary prostatic adenocarcinoma in 9 of 11 cases. Variable increases in immunoreactivity for AKR1C3 was also demonstrated in non-neoplastic changes in the prostate including chronic inflammation, atrophy and urothelial (transitional) cell metaplasia. We conclude that elevated expression of AKR1C3 is highly associated with prostate carcinoma. Although the biological significance of elevated AKR1C3 in prostatic carcinoma is uncertain, AKR1C3 may be responsible for the trophic effects of androgens and/or PGs on prostatic epithelial cells.

Decreased expression of smooth muscle alpha-actin results in decreased contractile function of the mouse bladder.

PURPOSE: Smooth muscle alpha-actin (SMalphaA) is an important actin isoform for functional contractility in the mouse bladder. Alterations in the expression of SMalphaA have been associated with a variety of bladder pathological conditions. Recently, a SMalphaA-null mouse was generated and differences in vascular tone and contractility were observed between wild-type and SMalphaA-null mice suggesting alterations in function of vascular smooth muscle. We used SMalphaA-null mice to explore the hypothesis that SMalphaA is necessary for normal bladder function. MATERIALS AND METHODS: Reverse transcriptase polymerase chain reaction, Western blotting and immunohistochemical staining were used to confirm the absence of SMalphaA transcript and protein in the bladder of SMalphaA-null mice. In vitro bladder contractility compared between bladder rings harvested from wild-type and SMalphaA-null mice was determined by force measurement following electrical field stimulation (EFS), and exposure to chemical agonists and antagonists including KCl, carbachol, atropine and tetrodotoxin. Resulting force generation profiles for each tissue and agent were analyzed. RESULTS: There was no detectable SMalphaA transcript and protein expression in the bladder of SMalphaA-null mice. Nine wild-type and 9 SMalphaA-null mice were used in the contractility study. Bladders from SMalphaA-null mice generated significantly less force than wild-type mice in response to EFS after KCl. Similarly, bladders from SMalphaA-null mice generated less force than wild-type mice in response to pretreatment EFS, and EFS after carbachol and atropine, although the difference was not significant. Surprisingly, the bladders in SMalphaA-null mice appeared to function normally and showed no gross or histological abnormalities. CONCLUSIONS: SMalphaA appears to be necessary for the bladder to be able to generate normal levels of contractile force. No functional deficits were observed in the bladders of these animals but no stress was placed on these bladders. To our knowledge this study represents the first report to demonstrate the importance of expression of SMalphaA in force generation in the bladder.

Ureterocystoplasty: indications for a successful augmentation.

PURPOSE: We evaluate the outcome of ureterocystoplasty based on preoperative evaluations. MATERIALS AND METHODS: We reviewed preoperative ultrasound, voiding cystourethrography and preoperative/postoperative urodynamic studies (UDS) in 64 patients undergoing ureterocystoplasty. RESULTS: Augmentation was performed with the distal 5 to 8 cm of a single megaureter in 8 patients without and 16 with grade 4 to 5/5 reflux. Median gain or loss in capacity and compliance was +0.14-fold and -0.11-fold, respectively. Re-augmentation has occurred or is pending in 23 cases (92%). Augmentation was performed in 40 patients with either a complete single or double collecting system. In 9 patients without reflux the diameter of the augmenting system was directly related to success. None of 6 with a ureteral diameter of greater than 1.5 cm required re-augmentation (median increase in bladder capacity and compliance 6 and 50-fold, respectively). Ureterocystoplasty was inadequate in 3 patients with a ureteral diameter of less than 1.5 cm and re-augmentation was required. In 31 patients with reflux, preoperative UDS of the entire system was beneficial. If the system had either normal or mild noncompliance (greater than 20 ml/cm H2O) ureterocystoplasty improved compliance 1-fold (6 cases) and re-augmentation not required. If UDS showed moderately or severely noncompliant system (less than 20 ml/cm H2O, 26 cases) ureterocystoplasty increased capacity and compliance by 0.4-fold (40%) and 0.25-fold (25%), respectively. Re-augmentation has occurred or is pending in 21 of 26 cases (81%). CONCLUSIONS: Ureterocystoplasty with any single or double collecting system is warranted in patients without reflux and a ureteral width greater than 1.5 cm, and in patients with reflux and mild noncompliance (greater than 20 ml/cm H2O) on UDS.

Injectable small intestinal submucosa: preliminary evaluation for use in endoscopic urological surgery.

PURPOSE: We evaluated the possible use of small intestinal submucosa in endoscopic urological surgery by assessing the smooth muscle regenerative capabilities and physical response of various forms of injectable small intestinal submucosa in the canine model. MATERIALS AND METHODS: In blinded fashion we injected small intestinal submucosa in 12 dogs submucosally under direct vision using a 20 gauge endoscopic needle. The 4 small intestinal submucosa formulations varied in harvesting method and sterilization technique. Animals were divided into groups of 3 and sacrificed 2 weeks, 6 weeks, 3 months and 6 months after surgery. Each injection site was analyzed grossly and histologically. Smooth muscle regeneration was identified by alpha-smooth muscle actin immunohistochemical staining. RESULTS: We identified 2 injectable small intestinal submucosa formulations that induced progressive smooth muscle regeneration at the site of submucosal injection compared with controls. De novo smooth muscle cells appeared in single cell aggregates as early as 6 weeks and in globular aggregates at 3 months. By 6 months early muscle bundle formation was noted. These 2 injectable small intestinal submucosa formulations also had the best submucosal volume preservation of about 25% of injected material during the study period. CONCLUSIONS: Injectable small intestinal submucosa promotes progressive submucosal smooth muscle regeneration in the canine bladder. The combined regenerative and bulking abilities of injectable small intestinal submucosa make this compound unique and novel. The clinical usefulness of injectable small intestinal submucosa for endoscopic correction of reflux and incontinence deserves further investigation.

Coculture of bladder urothelial and smooth muscle cells on small intestinal submucosa: potential applications for tissue engineering technology.

PURPOSE: Small intestinal submucosa is a xenogenic, acellular, collagen rich membrane with inherent growth factors that has previously been shown to promote in vivo bladder regeneration. We evaluate in vitro use of small intestinal submucosa to support the individual and combined growth of bladder urothelial cells and smooth muscle cells for potential use in tissue engineering techniques, and in vitro study of the cellular mechanisms involved in bladder regeneration. MATERIALS AND METHODS: Primary cultures of human bladder urothelial cells and smooth muscle cells were established using standard enzymatic digestion or explant techniques. Cultured cells were then seeded on small intestinal submucosa at a density of 1 x 105 cells per cm.2, incubated and harvested at 3, 7, 14 and 28 days. The 5 separate culture methods evaluated were urothelial cells seeded alone on the mucosal surface of small intestinal submucosa, smooth muscle cells seeded alone on the mucosal surface, layered coculture of smooth muscle cells seeded on the mucosal surface followed by urothelial cells 1 hour later, sandwich coculture of smooth muscle cells seeded on the serosal surface followed by seeding of urothelial cells on the mucosal surface 24 hours later, and mixed coculture of urothelial cells and smooth muscle cells mixed and seeded together on the mucosal surface. Following harvesting at the designated time points small intestinal submucosa cell constructs were formalin fixed and processed for routine histology including Masson trichrome staining. Specific cell growth characteristics were studied with particular attention to cell morphology, cell proliferation and layering, cell sorting, presence of a pseudostratified urothelium and matrix penetrance. To aid in the identification of smooth muscle cells and urothelial cells in the coculture groups, immunohistochemical analysis was performed with antibodies to alpha-smooth muscle actin and cytokeratins AE1/AE3. RESULTS: Progressive 3-dimensional growth of urothelial cells and smooth muscle cells occurred in vitro on small intestinal submucosa. When seeded alone urothelial cells and smooth muscle cells grew in several layers with minimal to no matrix penetration. In contrast, layered, mixed and sandwich coculture methods demonstrated significant enhancement of smooth muscle cell penetration of the membrane. The layered and sandwich coculture techniques resulted in organized cell sorting, formation of a well-defined pseudostratified urothelium and multilayered smooth muscle cells with enhanced matrix penetration. With the mixed coculture technique there was no evidence of cell sorting although matrix penetrance by the smooth muscle cells was evident. Immunohistochemical studies demonstrated that urothelial cells and smooth muscle cells maintain the expression of the phenotypic markers of differentiation alpha-smooth muscle actin and cytokeratins AE1/AE3. CONCLUSIONS: Small intestinal submucosa supports the 3-dimensional growth of human bladder cells in vitro. Successful combined growth of bladder cells on small intestinal submucosa with different seeding techniques has important future clinical implications with respect to tissue engineering technology. The results of our study demonstrate that there are important smooth muscle cell-epithelial cell interactions involved in determining the type of in vitro cell growth that occurs on small intestinal submucosa. Small intestinal submucosa is a valuable tool for in vitro study of the cell-cell and cell-matrix interactions that are involved in regeneration and various disease processes of the bladder.

Total urogenital complex mobilization in female patients with exstrophy.

PURPOSE: Female bladder exstrophy/epispadias has traditionally been approached in a staged fashion. This approach results in a vagina that remains in an abnormal position on the anterior abdominal wall. We present a surgical correction of the female exstrophy/epispadias urogenital complex with total mobilization that returns the vagina to its proper anatomical position. MATERIALS AND METHODS: Since 1997, 7 female patients presenting with variants of the exstrophy/epispadias complex have undergone surgical repair using total urogenital complex mobilization. Of the patients 1 newborn and 2 school-age children had classic bladder exstrophy, 2 school-age children had cloacal exstrophy and 2 school-age children had primary epispadias. Total urogenital complex mobilization involved treatment of the urethra and vagina as a single unit. Complete disassembly of the pelvic diaphragm or floor anterior to the rectum was required to reposition the urethra and vagina to their proper anatomical positions in the perineum. The pelvic diaphragm was then reconstructed anterior to the urogenital complex to recapitulate the normal female pelvic floor anatomy. RESULTS: All patients have an anatomically correct position of the urogenital complex. All the vaginas reached the perineum without the need for skin flaps. All patients have adequate vaginal caliber without evidence of stenosis. CONCLUSIONS: The female with exstrophy/epispadias has unique anatomical defects in the urogenital complex that require special attention. Anterior displacement of the bladder, urethra and vagina with concomitant lack of development of the anterior pelvic floor musculature make a single stage, total urogenital complex mobilization repair ideal for this population. The results of this technique have been functionally and cosmetically pleasing. Whether repositioning the urogenital complex into the normal anatomical position will improve bladder dysfunction and urinary continence rates, and decrease or eliminate the need for future surgery will only be known after further long-term followup has been completed.

Evaluation and treatment of children with neurogenic bladders.

The evaluation and treatment of children with neurogenic bladders can be difficult because of the complexity of the neurologic deficit and the subjectivity of the history and physical exam. The primary emphasis of the physicians caring for these children should be to preserve renal function and facilitate continence when possible. As knowledge of both normal and abnormal lower urinary-tract dynamics increases, so does the ability to care for children with abnormal bladder dynamics caused by various neurologic conditions. With recent advancements in medical and surgical treatment of the neurogenic bladder, most children can maintain adequate renal function and attain urinary continence. This article reviews the pertinent innervation, anatomy, and physiology of the lower urinary tract, and discusses current evaluation and treatment of children with neurogenic bladders.

Urologic tissue engineering with small-intestinal submucosa: potential clinical applications.

Small-intestinal submucosa (SIS) is a unique biomaterial that has been shown to induce tissue-specific regeneration in numerous organ systems. In the urinary tract, animal studies have demonstrated that SIS promotes functional bladder regeneration. Other preliminary studies have suggested that SIS may also be extremely useful for several other types of urologic surgery application where new tissue is needed or reinforcement of native structures is desired. This article reviews past and current work with SIS in the urinary tract and focuses on applications that will likely have future clinical utility.

Bioengineering organs using small intestinal submucosa scaffolds: in vivo tissue-engineering technology.

Tissue engineering is a promising field of research that has the potential to revolutionize urinary bladder reconstruction. Currently, two techniques for the induction of bladder regeneration are being researched. The first, the in vivo technique, involves the use of a biodegradable scaffold that the host bladder can use to remodel and regenerate. This technique takes advantage of the cell's natural ability to heal or regenerate itself back to a normal state. The second technology, the in vitro technique, involves establishment of primary cell cultures from the host's native bladder. These cells are seeded on a biodegradable scaffold to create a composite graft that is then transplanted back into the host for continuation of the regeneration process. Clearly, both techniques have advantages and disadvantages, and both will have some role in future urinary reconstruction. To date, the most successful results utilizing in vivo techniques have been with small intestinal submucosa (SIS). In this article, we discuss in vivo tissue engineering technology and the preclinical studies that have been performed utilizing SIS for urinary tract regeneration.

Characterization of cultured bladder smooth muscle cells: assessment of in vitro contractility.

PURPOSE: The contractile properties of in vitro cultured bladder smooth muscle cells (SMC) are unknown. This study characterized the in vitro contractile response of human and rat bladder SMC to several pharmacological agonists known to induce in vivo contraction of intact bladder muscle. MATERIALS AND METHODS: Human and rat bladder SMC were seeded separately within attached collagen lattices. Contractility of SMC was analyzed by measuring alterations in lattice diameter after exposure and release to the following contractile agonists: carbachol (10(-7)-10(-3) microM), calcium-ionophore (10 microM), lysophosphatidic acid (LPA) (1 microM), endothelin (0.1 microM), KCl (3.33 mmicroM) angiotensin II (10 microM), and serotonin (100 microM). Results were recorded as a mean reduction of the lattice diameter. In addition, immunohistochemical analysis for phenotypic markers of smooth muscle cell differentiation was performed on bladder SMC cultured within collagen lattices. Human palmar fascia fibroblasts, which have been previously well characterized by in vitro contractility and immunohistochemistry, were tested in parallel and used as controls for all the above experiments. RESULTS: Human SMC had significant contractile responses to calcium-ionophore (31% +/- 4 relative percent contraction, p <0.05), LPA (34% +/- 4, p <0.05), and endothelin (37 +/- 5%, p <05). There was no significant contraction in response to carbachol, angiotensin II, KCl, or serotonin. Rat bladder SMC had a similar contractile response but did not contract in response to endothelin. In contrast to human and rat bladder SMC, fibroblasts did not contract to calcium-ionophore. CONCLUSIONS: In vitro cultured bladder SMC demonstrate loss of contractile response to normal in vivo pharmacologic agonists. Both human and rat bladder SMC can be distinguished in vitro from fibroblasts based upon their lack of contractile response to calcium- ionophore. These results demonstrate the ability to further characterize cultured bladder SMC with in vitro contractility. Further characterization is essential if we are to advance our understanding of the clinical applicability of in vitro studies utilizing cultured bladder SMC.

Small-intestinal submucosa for bladder augmentation: a review of preclinical studies.

The need to find an alternative to the use of bowel for urinary reconstruction has renewed research interests involving bladder regeneration. Historically, alloplastic and biodegradable materials have demonstrated bladder regeneration; however, high complication rates and unreliable regenerative results have prevented any of these materials from being used clinically. Small-intestinal submucosa (SIS) is an acellular, nonimmunogenic, biodegradable, xenogeneic, collagen-based material that is derived from the submucosa layer of porcine small intestine. SIS has demonstrated regenerative capacities in multiple organ systems, including the aorta, vena cava, ligaments, tendons, abdominal wall, and skin. SIS has also demonstrated long-term reliable regenerative results in the rat and canine bladder-augmentation models. This article reviews the preclinical studies involving the use of SIS for bladder augmentation.

Artificial urinary sphincter in the treatment of urinary incontinence: preoperative urodynamics do not predict the need for future bladder augmentation.

PURPOSE: The artificial urinary sphincter has been used to treat urinary incontinence in pediatric patients with neurogenic bladders secondary to myelodysplasia. Frequently bladder augmentation is performed in conjunction with the artificial urinary sphincter implantation. Identifying patients with adequate urinary reservoirs who are candidates for implantation without bladder augmentation is a clinical challenge. We reviewed our experience with the artificial urinary sphincter in children with myelodysplasia to determine whether preoperative urodynamic findings predict the need for future augmentation cystoplasty. MATERIALS AND METHODS: We identified 38 patients younger than 18 years at artificial urinary sphincter implantation who did not undergo augmentation enterocystoplasty before or at implantation. We evaluated preoperative bladder capacity and compliance to determine whether these standard preoperative urodynamic measurements predict the eventual need for bladder augmentation in these patients. RESULTS: In the 15 patients who required eventual bladder augmentation after artificial urinary sphincter implantation mean bladder capacity plus or minus standard deviation was 62.9+/-29.9% of age expected capacity and mean bladder compliance was 8.0+/-4.8 ml./cm. water. In the 23 patients who did not require eventual bladder augmentation mean bladder capacity was 59.2+/-25.4% of age expected capacity and compliance was 7.0+/-3.3 ml./cm. water. There was no statistically significant difference between the 2 groups. CONCLUSIONS: Standard preoperative urodynamics do not predict the patients who undergo isolated artificial urinary sphincter implantation and eventually require bladder augmentation.

Wilms' tumor with renal cell carcinoma overgrowth in a 3-year-old child.

Wilms' tumors that contain features of both renal cell carcinoma and classic Wilms' tumor histology are rare. Even though nine such cases have been previously reported in the literature, we report the first case of a Wilms' tumor with an overwhelmingly renal cell carcinoma histologic pattern.

Rabbit urethral regeneration using small intestinal submucosa onlay grafts.

OBJECTIVES: To determine if small intestinal submucosa (SIS) can evoke urethral regeneration. METHODS: Twenty male white New Zealand rabbits were assigned to one of three experimental groups. Group 1 (n = 4) underwent simple urethrotomy and closure. Group 2 (n = 8), a second control group, underwent an onlay urethroplasty with a graft of full-thickness preputial skin from the host rabbit. Group 3 (n = 8) underwent an onlay urethroplasty with an SIS graft. RESULTS: All eight SIS onlay grafts promoted regeneration of the normal rabbit epithelium supported by a well-vascularized collagen and smooth muscle backing. Preputial free onlay grafts maintained a keratinizing squamous cell epithelium with a poor supportive backing, which resulted in the formation of urethral diverticulum. CONCLUSIONS: SIS onlay patch grafts for urethroplasty promote rabbit urethral regeneration.