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.

Mitrofanoff continent catheterizable conduits: top down or bottom up?

OBJECTIVE: During augmentation and Mitrofanoff procedures, conduits are usually implanted into the posterior bladder wall. Anatomical considerations may necessitate an anterior conduit. To compare the relative drainage efficiency in patients with posterior and anterior conduits, we studied their rates of bladder stone formation and urinary tract infection (UTI). MATERIALS AND METHODS: A retrospective chart review identified exstrophy patients who underwent augmentation and Mitrofanoff between 1991 and 2003. Patients with 3 years or greater follow-up were included. Fifty-four patients fit this criterion, with a conduit implanted anteriorly (33) or posteriorly (21). We compared rates of bladder stone formation and UTI. Stomal revisions and the status of the bladder neck were also noted. RESULTS: Stone formation and UTI rates were higher in the anterior conduits, although only UTI showed a statistically significant difference. Patient demographics were similar between the two groups, including age and sex. The rates of stomal complications and the bladder neck status were also similar. CONCLUSIONS: Patients with anterior conduits had an increased risk of UTI and bladder stone formation compared to those with posterior conduits, although this was not significant in the case of bladder stone rate. This may indicate sub-optimal bladder drainage and should be addressed with careful preoperative counseling and close follow-up.

Polyps in the exstrophic bladder. A cause for concern?

PURPOSE: The role of environmental injury in carcinogenesis is widely recognized. Malignancy in exstrophic bladders has been reported most frequently in untreated adults and those undergoing surgical treatments which involve the mixing of fecal and urinary streams. The question of whether the closed exstrophic bladder has a similar potential for malignancy has not been resolved. The polypoid appearance of the exstrophic bladder template raises the concern of premalignant lesions. We characterized the histology of these lesions and analyzed their microscopic features with particular reference to predisposition for dysplasia. In doing so, we attempt to address the aforementioned question and set the stage for definitive quantification of the risk of malignancy in these patients with careful, long-term followup. MATERIALS AND METHODS: Under institutional board review, the slides of 38 patients with classic bladder exstrophy who had polyps excised at the time of closure were reviewed by a single genitourinary pathologist (JIE). The most common findings were reported for polyps resected at primary and secondary closure, respectively, and a comparative analysis was performed. RESULTS: Of the 38 cases 24 were primary closures and 14 were secondary closures. Six of the primary closures were delayed by 6 weeks or greater. The 2 basic types of polyps observed were fibrotic and edematous. Both types were associated with overlying reactive squamous metaplasia in approximately 50% of cases. Varying degrees of fixed on file Brunn's nests, cystitis cystica and cystitis glandularis were noted. Cystitis glandularis was observed in a significantly greater percentage of secondary closures (p = 0.0014). CONCLUSIONS: Although no dysplasia was noted, cystitis glandularis is associated with the development of adenocarcinoma of the bladder. The finding of cystitis glandularis suggests a more severe epithelial injury and it follows that the significant majority of these cases (10 of 14, 71.4%) were observed with polyps resected during secondary closure. These patients warrant future surveillance with urine cytology and cystoscopy as they enter adult life.

A high-grade primary leiomyosarcoma of the bladder in a survivor of retinoblastoma.

Second nonocular malignancies develop with increased incidence in patients with hereditary retinoblastoma. Osteosarcoma is by far the most common type with an incidence of up to 50%, followed by soft tissue sarcomas. Visceral leiomyosarcoma is extremely rare and only 2 cases have been reported in the past 2 decades, one in the liver and another one in the urinary bladder, both of which developed after cyclophosphamide therapy. Here we report a case of vesical leiomyosarcoma that was diagnosed in a 49-year-old woman 47 years after the diagnosis of a hereditary retinoblastoma. The patient's retinoblastoma was treated with unilateral enucleation without adjuvant radiation or chemotherapy. We believe that this is the first report of vesical leiomyosarcoma occurring in a patient with retinoblastoma without a prior history of radiation or chemotherapy. This report is significant not only because of the rarity of vesical leiomyosarcoma as a second nonocular tumor in retinoblastoma patients, but also because of the infrequency of vesical leiomyosarcoma in general. We also investigated the potential molecular pathogenesis of the leiomyosarcoma.

Antenatally diagnosed cloacal exstrophy variant with intravesical phallus in a twin pregnancy.

We report a rare case of covered cloacal exstrophy variant with a hemiphallus trapped within partially closed bladder halves. The persistence of the cloacal membrane until at least 18 weeks' gestation, confirmed by antenatal ultrasound scanning, is discordant with existing theories of embryogenesis of cloacal exstrophy. The clinical presentation highlights the need for careful assessment, before and during surgery, to obtain a complete understanding of the anatomic defect before gender assignment and appropriate reconstructive efforts. A multispecialty approach and antenatal counseling are important, especially when only one fetus of twins has major birth defects.

Laparoscopic extravesicular ureteral reimplantation for vesicoureteral reflux: recent technical advances.

Ureteral reimplantation is an effective treatment for primary vesicoureteral reflux. Recent efforts have been directed toward reducing the perioperative morbidity of open reimplantation. We have refined the technique of laparoscopic extravesical ureteral reimplantation with emphasis on minimal tissue dissection, achieving reliable detrusor closure, and downsizing ports and instruments. With our current technique, excellent results comparable to those of established open procedures are achieved, while postoperative discomfort and the recovery period are significantly reduced. The laparoscopic technique of ureteral reimplantation is described, with emphasis on key technical modifications crucial to the ease of performance and a successful outcome.

Exploratory data analysis groupware for qualitative and quantitative electrophoretic gel analysis over the Internet-WebGel.

Many scientists use quantitative measurements to compare the presence and amount, of various proteins and nucleotides among series of one- and two-dimensional (1-D and 2-D) electrophoretic gels. These gels are often scanned into digital image files. Gel spots are then quantified using stand-alone analysis software. However, as more research collaborations take place over the Internet, it has become useful to share intermediate quantitative data between researchers. This allows research group members to investigate their data and share their work in progress. We developed a World Wide Web group-accessible software system, WebGel, for interactively exploring qualitative and quantitative differences between electrophoretic gels. Such Internet databases are useful for publishing quantitative data and allow other researchers to explore the data with respect to their own research. Because intermediate results of one user may be shared with their collaborators using WebGel, this form of active data-sharing constitutes a groupware method for enhancing collaborative research. Quantitative and image gel data from a stand-alone gel image processing system are copied to a database accessible on the WebGel Web server. These data are then available for analysis by the WebGel database program residing on that server. Visualization is critical for better understanding of the data. WebGel helps organize labeled gel images into montages of corresponding spots as seen in these different gels. Various views of multiple gel images, including sets of spots, normalization spots, labeled spots, segmented gels, etc. may also be displayed. These displays are active and may be used for performing database operations directly on individual protein spots by simply clicking on them. Corresponding regions between sets of gels may be visually analyzed using Flicker-comparison (Electrophoresis 1997, 18, 122-140) as one of the WebGel methods for qualitative analysis. Quantitative exploratory data analysis can be performed by comparing protein concentration values between corresponding spots for multiple samples run in separate gels. These data are then used to generate reports on statistical differences between sets of gels (e.g., between different disease states such as benign or metastatic cancers, etc.). Using combined visual and quantitative methods, WebGel can help bridge the analysis of dissimilar gels which are difficult to analyze with stand-alone systems and can serve as a collaborative Internet tool in a groupware setting.

Nuclear shape and nuclear matrix protein composition in prostate and seminal vesicles.

OBJECTIVES: The nucleus controls cell function and behavior. The nuclear matrix determines internal nuclear changes. Two-dimensional gel electrophoresis is the reference standard for the analysis of nuclear matrix protein (NMP) composition. Differences in NMP composition should therefore be reflected by changes in nuclear shape. We investigated the differences in NMP composition and nuclear morphometry of the prostate and seminal vesicles. Both tissues are androgen-dependent sex accessory organs with completely different biologic behavior. METHODS: High-resolution two-dimensional gel electrophoresis and silver staining were used to evaluate NMP composition from histologically normal prostate and seminal vesicle epithelial cells. Nuclear morphometry, performed using a computer-assisted image analysis system, described the distribution, variability, and extremes of nuclear shape. RESULTS: NMP composition analysis demonstrated that both tissues have a similar NMP composition, and tissue-specific NMPs that were consistently present in all specimens of each tissue could not be demonstrated. Nuclear morphometry showed a significantly greater heterogeneity in nuclear shape in the seminal vesicles than in the prostate. CONCLUSIONS: The striking similarity of the NMP composition demonstrates the close biologic relationship between prostate and seminal vesicle tissue. The similar NMP composition does not correlate with the marked alterations in nuclear shape and structure between these tissues. Therefore, nuclear morphometry may depict differences in the functional state of a similar set of NMPs, shown by two-dimensional gel electrophoresis, which may be responsible for the different biologic behavior of these tissues.

Feasibility of total intravesical endoscopic surgery using mini-instruments in a porcine model.

BACKGROUND AND OBJECTIVES: The aim of minimally invasive approaches to vesicoureteral reflux, such as endoscopic trigonoplasty, is to lower the morbidity of open procedures without compromising the results. Initial successes have not been sustained, mainly because of trigonal splitting, which results in the ureteral orifices returning to their preoperative positions. This study was designed to address trigonal splitting by mobilizing the ureters before repositioning them and to evaluate the feasibility of accomplishing this intravesically with 2- to 3-mm endoscopic mini-instruments. METHODS: Bilateral vesicoureteral reflux was surgically created in 10 minipigs. After radiologic confirmation of success 4 weeks later, modified trigonoplasty was performed by endoscopic intravesical mobilization of both ureters and incision of the trigonal mucosa using 2-mm instruments. The ureteral orifices were then advanced toward the midline and sutured in place. The initial surgical techniques were modified to permit the entire procedure to be performed endoscopically in the last four minipigs. Cystograms and intravenous urograms were obtained 4 weeks later. RESULTS: Two minipigs died postoperatively. Six of the remaining eight had persistent reflux, including three of the four in the group treated completely by endoscopic means. None of the dissected ureters showed evidence of stricture or necrosis. CONCLUSIONS: Although the procedure was not successful in correcting reflux in this model, this study demonstrates the feasibility of endoscopic ureteral mobilization. With current instrumentation, there is no significant technical obstacle to complete intravesical endoscopic surgery, including ureteral reimplantation.

Differential nuclear matrix protein expression in prostate cancers: correlation with pathologic stage.

PURPOSE: Nuclear Matrix Proteins (NMP) have been shown to be tissue and cell-type specific. Several unique NMPs have been investigated in various cancerous tissues, including prostate, bladder and kidney, and some are presently utilized as tumor markers. This study was aimed at characterizing the differential NMP expression in the pathologically more aggressive prostate cancers. METHODS: High resolution two-dimensional gel electrophoresis and silver staining was used to elucidate the NMP distribution of fresh prostate cancer nuclei, obtained from 39 radical prostatectomy specimens, surgically removed from men with clinically localized prostate cancer. Based on the final pathological grading, specimens were grouped according to predicted prognosis: poor--with seminal vesicle (SV) or lymph node (LN) involvement or established capsular penetration (ECP) with gleason score >7; intermediate--organ confined (OC) or focal capsular penetration (FCP) with gleason score 7 or ECP with gleason score 6; and good--with OC or FCP and gleason score <7. RESULTS: A specific charged protein (YL-1) of molecular weight 76 kD and isoelectric range 6.0-6.6 was found to be consistently present in 19 of 19 aggressive cancers. It was present only in 1 of 10 in the group with good prognosis and weakly positive in 9 of 10 in the intermediate group. CONCLUSIONS: Within this preliminary study, the expression of YL-1 appears to be related to aggressive prostate cancer, suggesting a potential marker of poor prognosis for clinically localized prostate cancer. Further characterization of the identity and function of this NMP is needed to fully ascertain its clinical potential.

Inflammatory (pseudosarcomatous) myofibroblastic tumor of the bladder.

We present a case of inflammatory (pseudosarcomatous) myofibroblastic tumor of the bladder in a child, along with a review of the literature. The benign nature of this rare disorder needs to be recognized so that superfluous radical therapy can be avoided. The clinical features and microscopic, ultrastructural, and immunohistochemical characteristics that help to identify this entity are described. To date, 72 such cases involving the bladder have been reported in the literature including the present one.

Spinal abnormalities in classic bladder exstrophy.

OBJECTIVE: To determine the frequency and clinical sequelae of significant spinal malformations in children born with classic bladder exstrophy. PATIENTS AND METHODS: All patients evaluated or treated for classic bladder exstrophy at this institution were reviewed retrospectively. Radiographs or reports pertinent to the spine were retrieved and reviewed with a paediatric radiologist and all vertebral abnormalities categorized. Clinical charts of those with spinal anomalies were reviewed to determine any clinical neurological disorders associated with the radiographic findings. RESULTS: Of 423 patients with classic bladder exstrophy who were identified, 299 had radiographs or reports available for adequate review. Of these, 34 (11%) normal variants, e.g. spina bifida occulta and lumbarization or sacralization of vertebrae, were identified. Abnormalities of spinal curvature were identified in eight patients (2.7%), all with uncomplicated scoliosis. Spinal dysraphism was diagnosed in 12 patients (4%) and included myelomeningocele, lipomeningocele, scimitar sacrum, posterior laminal defects in two or more vertebrae, vertebral fusion and hemivertebrae. The one patient with myelomeningocele had clinical neurological dysfunction, giving an overall incidence of 0.3%. CONCLUSIONS: Spinal anomalies, excluding normal variants, occur in children born with classic bladder exstrophy at a rate of about 6.7%. The incidence of this association is much less than that for cloacal exstrophy. Although rare, neurological dysfunction can occur in the case of spinal dysraphism. Paediatric urologists and neurologists should be aware of this significant difference between patients with classic bladder and cloacal exstrophy to properly diagnose, evaluate and treat the attendant neurological problems.

Partial resection of symphysis: an aid in radical prostatectomy.

PURPOSE: Resection of a posterior symphyseal osteophyte during radical retropubic prostatectomy was evaluated. MATERIALS AND METHODS: The surgical technique is described. RESULTS: A favorable experience was noted in 10 patients with partial symphyseal resection. CONCLUSIONS: Partial symphyseal resection of an osteophyte protruding from the posterior symphysis can facilitate radical retropubic prostatectomy by improving visualization of the apex of the prostate.

Testicular implants.

Testicular implants have been in use for more than 50 years with an excellent record of safety and efficacy. The controversy concerning the use of silicone prosthetics in breast implants also affected testicular implants. There is no conclusive evidence associating connective tissue disorders, autoimmunity, or malignancy with silicone implants. Studies show silicone leakage from these implants, but long-term follow-up is required to identify the significance of this finding. Saline-filled silastic shell testicular prostheses will be implanted as part of an ongoing study to monitor various safety parameters, as required by the Food and Drug Administration.