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.

Urinary tract infection after voiding cystourethrogram.

BACKGROUND: Reported rates of post-procedural urinary tract infection (ppUTI) after voiding cystourethrogram (VCUG) are highly variable (0-42%). OBJECTIVE: This study aimed to determine the risk of ppUTI after cystogram, and evaluate predictors of ppUTI. STUDY DESIGN: A retrospective cohort study of children undergoing VCUG or radionuclide cystogram (henceforth 'cystogram') was conducted. Children with neurogenic bladder who underwent cystogram in the operating room and without follow-up at the study institution were excluded. Incidence of symptomatic ppUTI within 7 days after cystogram was recorded. Predictors of ppUTI were evaluated using univariate statistics. RESULTS: A total of 1108 children (54% female, median age 1.1 years) underwent 1203 cystograms: 51% were on periprocedural antibiotics, 75% had a pre-existing urologic diagnosis (i.e., vesicoureteral reflux (VUR) or hydronephrosis; not UTI alone), and 18% had a clinical UTI within 30 days before cystogram. Of the cystograms, 41% had an abnormal cystogram and findings included VUR (82%), ureterocele (6%), and diverticula (6%). Twelve children had a ppUTI (1.0%; four girls, five uncircumcised boys, three circumcised boys; median age 0.9 years). Factors significantly associated with diagnosis of a ppUTI (Summary fig.) included: pre-existing urologic diagnosis prior to cystogram (12/12, 100% of patients with ppUTI), abnormal cystogram results (11/12, 92%), and use of periprocedural antibiotics (11/12, 92%). All 11 children with an abnormal cystogram had VUR ≥ Grade III. However, among all children with VUR ≥ Grade III, 4% (11/254) had a ppUTI. DISCUSSION: This is the largest study to date that has examined incidence and risk factors for ppUTI after cystogram. The retrospective nature of the study limited capture of some clinical details. This study demonstrated that the risk of ppUTI after a cystogram is very low (1.0% in this cohort). Having a pre-existing urologic diagnosis such as VUR or hydronephrosis was associated with ppUTI; therefore, children with moderate or high-grade VUR on cystogram may be at highest risk. Development of ppUTI after cystogram also highlighted the potential for a delay in diagnosis or oversight of a healthcare-associated infection due to several factors: 1) cystograms may be ordered, performed/interpreted, and followed up by multiple different providers; and 2) such infections are not captured by traditional healthcare-associated infection surveillance strategies. CONCLUSIONS: The risk of ppUTI after a cystogram is very low. Only children with pre-existing urologic diagnoses developed ppUTI in this study. This study's findings suggest that children undergoing a cystogram should not be given peri-procedural antibiotic prophylaxis for the sole purpose of ppUTI prevention.

Lipomyelomeningocele for the urologist: Should we view it the same as myelomeningocele?

INTRODUCTION: The primary urologic objectives for lipomyelomeningocele (LMM) and myelomeningocele (MM) are preserving renal integrity and achieving continence. Due to this common ground, LMM and MM are urologically treated the same. However, unlike MM, LMM may present with no evident functional concerns. Indications for and timing of tethered cord release (TCR) in LMM are therefore controversial. Long-term urologic outcomes are not well defined. OBJECTIVE: Expectations for continence and potential for intermittent catheterization (CIC) following TCR in LMM are important for realistically counseling families regarding future needs. The present study aimed to identify prognostic factors for continence and need for CIC in LMM. STUDY DESIGN: The present study retrospectively identified 143 patients from the multidisciplinary clinic who underwent TCR for LMM between 1995 and 2010. Concomitant anorectal/genitourinary anomalies, filar lipoma, fatty filum, previous TCR, and follow-up <1 year were excluded. Analysis was limited to those toilet trained or aged ≥6 years at latest follow-up. Lipomyelomeningocele was classified as dorsal, distal, transitional or chaotic. Pre- and post-TCR urologic status was assessed. Ability to achieve urinary continence, with or without CIC, was the primary outcome, and need for CIC was the secondary outcome of interest. RESULTS: A total of 56 patients met inclusion criteria. Median age at TCR was 4.4 months (range 1.0-224.0) with a median follow-up of 10.7 years (range 1.3-19.1); 68% were asymptomatic at presentation. Clinical symptoms were urologic in 7%. At the latest follow-up, 86% of patients were continent spontaneously or with CIC (Summary Fig.). Of the four patients who presented with urologic symptoms, all were continent, but three required CIC. Overall, 23% of patients required CIC. Median age at CIC initiation was 7.6 years (range 1.6-17.4). Long-term continence was not associated with any demographic, anatomic, surgical or functional variable. Need for CIC at latest follow-up was associated with symptomatic presentation, partial TCR, transitional lipoma, and high-risk pre-operative urodynamics. DISCUSSION: In this series of primary TCR for LMM, where 93% of patients were urologically asymptomatic before TCR, prospects for continence were excellent. No studied parameter clearly impacted continence; however, need for CIC was associated with multiple variables. CONCLUSIONS: Clear predictors for continence after TCR will require additional long-term patient outcomes. Families can anticipate 23% likelihood of CIC, which is considerably less than in MM, but long-term urologic follow-up is still strongly recommended.

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.

Prenatal pharmacogenomics: a promising area for research.

Clinical applications of prenatal genetic screening currently focus on detection of aneuploidy and other genetic diseases in the developing fetus. Growing evidence suggests that the fetal genome may also be informative about fetal exposures through contributions to placental transport as well as placental and fetal metabolism. Possible clinical applications of prenatal pharmacogenomic screening include prospective optimization of medication selection and dosage, as well as retrospective assessment of whether a fetus was previously exposed to significant risk. Newly available noninvasive methods of prenatal genetic screening mean that relevant fetal genotypes could be made available to obstetricians for use in management of a current pregnancy. This promising area for research merits more attention than it has thus far received.The Pharmacogenomics Journal advance online publication, 10 May 2016; doi:10.1038/tpj.2016.33.

Successful term pregnancy in an intestine-pancreas transplant recipient with chronic graft dysfunction and parenteral nutrition dependence: a case report.

Pregnancy after solid organ transplantation is becoming more common, with the largest recorded numbers in renal and liver transplant recipients. Intestinal transplantation is relatively new compared to other solid organs, and reports of successful pregnancy are far less frequent. All pregnancies reported to date in intestinal transplant recipients have been in women with stable graft function. The case reported here involves the first reported successful term pregnancy in an intestine-pancreas transplant recipient with chronic graft dysfunction and dependence on both transplant immunosuppression and parenteral nutrition (PN) at the time of conception. Pregnancy was unplanned and unexpected in the setting of chronic illness and menstrual irregularities, discovered incidentally on abdominal ultrasound at approximately 18 weeks' gestation. Rapamune was held, tacrolimus continued, and PN adjusted to maintain consistent weight gain. A healthy female infant was delivered vaginally at term. Medical complications during pregnancy included anemia and need for tunneled catheter replacements. Ascites and edema were improved from baseline, with recurrence of large volume ascites shortly after delivery. Successful pregnancy is possible in the setting of transplant immunosuppression, chronic intestinal graft dysfunction, and long-term PN requirement, but close monitoring is required to ensure the health of mother and child.

Repair of megameatus: a modified approach.

OBJECTIVE: To demonstrate surgical reconstruction of a megameatus variant of hypospadias by using a modified, patient-specific approach. METHODS: An 8-month-old male had a megameatus, which was discovered after newborn circumcision. In repair of megameatus, it is important to recognize the full extent to which the distal urethra is widened, in order to avoid inadvertent urethrotomy during mobilization of the glans wings and skin immediately proximal to the glans. In this case, a small wedge of tissue was excised from the ventral aspect of the urethra, and a midline relaxing incision of the urethral plate was made. Standard principles of hypospadias repair should be followed, with tension-free urethral tubularization, coverage of the neourethra with well-vascularized tissue, and adequate mobilization of the glans wings to allow midline reconstruction without compression of the underlying neourethra. RESULTS: There were no perioperative or postoperative complications in this case. The urethral meatus was positioned near the tip of the glans penis, and there was no evidence of meatal stenosis or urethrocutaneous fistula at 5-months follow-up. CONCLUSION: Each case of megameatus is unique, and a variety of surgical techniques can be used in formulating an approach that achieves optimal cosmetic and functional outcomes.

Evaluation of the United States pediatric urology workforce and fellowships: a series of surveys performed in 2006-2010.

OBJECTIVE: In the US, there has been an evolution in the practice of pediatric urology from a primary academic sub-specialty focused on reconstruction of major congenital genitorurinary abnormalities to a mixed academic and private practice that serves as the primary care giver for all pediatric urologic concerns. The estimated manpower needs were unable to be resolved, due to our inability to determine the impact of sub-specialty certification on referral patterns, along with the failure to embrace the use of physician extenders. Here, we review a series of surveys performed in 2006-2010 regarding the sub-specialty of pediatric urology. MATERIALS AND METHODS: The four surveys focused on workforce needs, appraised the financial impact of educational debt on the pediatric urology community, and evaluated concerns of the current fellows in training. RESULTS: The median financial income for a pediatric urologist, the resident's educational debt load, and a desire of the fellows to have an open dialog with the urologic community regarding the merits of the research year are revealed. CONCLUSION: We have identified that the ability to recruit fellows into our field is dependent upon a combination of factors: interest in the field, job availability in relationship to geographic locations, mentoring, concerns regarding financial/familial hardships encountered during a 2-year fellowship, and the lack of increased financial reimbursement for the extra training required.

Magnetic resonance angiography for the nonpalpable testis: a cost and cancer risk analysis.

PURPOSE: For the unilateral nonpalpable testis standard management is open surgical or laparoscopic exploration. An ideal imaging technique would reliably identify testicular nubbins and safely allow children to forgo surgical exploration without compromising future health or fertility. Our goal was to perform a cost and risk analysis of magnetic resonance angiography (MRA) for unilateral nonpalpable cryptorchid testes. MATERIALS AND METHODS: A search of the English medical literature revealed 3 studies addressing the usefulness of MRA for the nonpalpable testicle. We performed a meta-analysis and applied the results to a hypothetical set of patients using historical testicular localization data. Analysis was then performed using 3 different management protocols-MRA with removal of testicular nubbin tissue, MRA with observation of testicular nubbin tissue and diagnostic laparoscopy. A cancer risk and cost analysis was then performed. RESULTS: MRA with observation of testicular nubbin tissue results in 29% of patients avoiding surgery without any increased cost of care. Among the 29% of boys with testicular nubbins left in situ and observed the highest estimated risk was 1 in 300 of cancer developing, and 1 in 5,300 of dying of cancer. CONCLUSIONS: A protocol using MRA with observation of inguinal nubbins results in nearly a third of boys avoiding surgical intervention at a similar cost to standard care without any significant increased risk of development of testis cancer.

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.

Release of [Met5]enkephalin from the spinal cord by intraventricularly administered endomorphin-2, but not endomorphin-1 in the anesthetized rat.

Effects of intraventricular injection of endomorphin-1, endomorphin-2 and beta-endorphin on the release of immunoreactive [Met(5)]enkephalin from the spinal cord were studied in pentobarbital anesthetized rats. Intraventricular injection of endomorphin-2, but not endomorphin-1, caused an increased release of immunoreactive [Met(5)]enkephalin in the spinal perfusates. Beta-endorphin given intraventricularly also increased the release of immunoreactive [Met(5)]enkephalin in an amount 15-fold higher than that produced by endomorphin-2. The increase of the release of immunoreactive [Met(5)]enkephalin induced by endomorphin-2 was blocked by mu-opioid receptor antagonist CTOP. Our result suggests that endomorphin-2 stimulates another subtype of mu-opioid receptor different from that acted by endomorphin-1 at the supraspinal site and subsequently increases the release of [Met(5)]enkephalin from the spinal cord.

Specific activation of the alpha 7 nicotinic acetylcholine receptor by a quaternary analog of cocaine.

Effects of cocaine and cocaine methiodide were evaluated on the homomeric alpha 7 neuronal nicotinic receptor (nAChR). Whereas cocaine itself is a general nAChR noncompetitive antagonist, we report here the characterization of cocaine methiodide, a novel selective agonist for the alpha 7 subtype of nAChR. Data from (125)I-alpha-bungarotoxin binding assays indicate that cocaine methiodide binds to alpha 7 nAChR with a K(i) value of approximately 200 nM while electrophysiology studies indicate that the addition of a methyl group at the amine moiety of cocaine changes the drug's activity profile from inhibitor to agonist. Cocaine methiodide activates alpha 7 nAChR with an EC(50) value of approximately 50 microM and shows comparable efficacy to ACh in oocyte experiments. While agonist effects are specific for the alpha 7 neuronal nAChR and are not observed with heteromeric neuronal or skeletal muscle nAChR, antagonist effects are present for heteromeric nAChR combinations. Studies of PC12 cells transiently transfected with human alpha 7 cDNA and expressing a variety of functional nicotinic receptor subtypes confirm the specificity of cocaine methiodide agonist effects. Our results indicate that a quaternary structural derivative of cocaine can be used as a specific agonist for the alpha 7 subtype of neuronal nicotinic receptor.

Lamina muscularis propria thickness of renal pelvis predicts radiological outcome of surgical correction of ureteropelvic junction obstruction.

PURPOSE: We examine if there is a relationship between the histopathology of the renal pelvis and postoperative radiological findings in children with ureteropelvic junction obstruction. MATERIALS AND METHODS: The records of 220 patients who underwent pyeloplasty for isolated ureteropelvic junction obstruction between 1988 and 1996 were retrospectively reviewed, and 41 (42 kidneys) were identified who had adequate histological specimens and postoperative radiographic studies (ultrasonography and/or well tempered renogram) for examination. Histological features of the lamina muscularis propria from the renal pelvis were correlated with the radiographic outcome after pyeloplasty. RESULTS: Lamina muscularis propria thickness of the renal pelvis correlated significantly with radiological improvement. All kidneys with renal pelvic lamina muscularis propria thickness less than 250 microm. showed radiological improvement at 3 to 6 months postoperatively, those with thickness between 250 and 350 microm. had improvement at 9 months and those with lamina thickness greater than 350 microm. had a significantly worse outcome at all observation points. At 3 and 6 months postoperatively 16 of 30 (53%) and 23 of 34 (68%) children with radiological improvement had a mean lamina muscularis propria thickness of 252 +/- 131.5 microm. and 263 +/- 122.8 microm., respectively, while the remaining unimproved 14 and 12 patients had a mean thickness of 374 +/- 64.3 microm. (p <0.01) 372 +/- 66.1 microm. (p <0.05), respectively. CONCLUSIONS: The lamina muscularis propria thickness of the renal pelvic wall can provide insight to the expected time of postoperative improvement on radiological studies in children with ureteropelvic junction obstruction.

Osteogenesis imperfecta: mode of delivery and neonatal outcome.

OBJECTIVE: To evaluate the pregnancy characteristics, methods of delivery, and neonatal outcomes of fetuses affected by osteogenesis imperfecta. METHODS: We reviewed medical records of 1016 individuals whose cells were sent to the University of Washington Collagen Diagnostic Laboratory between 1987 and 1994 for confirmation of diagnoses of osteogenesis imperfecta. Information and neonatal records were available for 167 of those pregnancies. From those we identified method(s) of prenatal detection, delivery method, and neonatal complications, including survival and acquisition of new fractures, and related them to type of delivery. RESULTS: The cesarean delivery rate was 54%, most of them (53%) for nonvertex presentation and fewer than 15% because of an antenatal diagnoses of osteogenesis imperfecta. There was an unusually high rate of breech presentation at term (37%). In infants with nonlethal forms of osteogenesis imperfecta, 24 of 59 (40%) delivered by cesarean and 17 of 53 (32%) delivered vaginally had new fractures (chi(2) =.89; P =.3). Among 55 infants with the most severe form, 24 of 31 delivered by cesarean and 21 of 24 delivered vaginally died within 2 weeks of birth. CONCLUSION: Cesarean delivery did not decrease fracture rates at birth in infants with nonlethal forms of osteogenesis imperfecta nor did it prolong survival for those with lethal forms. Prenatal diagnosis did not influence mode of delivery in most instances. Most cesarean deliveries were done for usual obstetric indications.

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.

The workforce in otolaryngology-head and neck surgery: moving into the next millennium.

OBJECTIVE: The goal was to examine the current scope of otolaryngologists' practices, their geographic distribution, and the roles otolaryngologists and other specialists play in caring for patients with otolaryngic and related conditions of the head and neck. STUDY DESIGN: A large national survey and administrative claims databases were examined to develop practice profiles and compile a physician supply for otolaryngology. A focus group of otolaryngologists provided information to model future scenarios. RESULTS: The current and predicted workforce supply and demographics are at a satisfactory level and are decreasing as a proportion of the increasing population. Empiric data analysis supports the diverse nature of an otolaryngologist's practice and the unique role for otolaryngologists that is not shared by many other providers. Together with the focus group results, the study points to areas for which more background and training are warranted. CONCLUSIONS: This study represents a first step in a process to form coherent workforce recommendations for the field of otolaryngology.

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.