Vaginal discharge and bleeding in girls younger than 6 years.

PURPOSE: Persistent unexplained vaginal discharge or bleeding in the pediatric population may be the only manifestation of a serious underlying medical or social problem. Therefore, these symptoms require careful and complete evaluation to identify the primary pathology accurately. We retrospectively reviewed charts of patients who presented for evaluation of persistent vaginal discharge or bleeding to determine if noninvasive imaging was a sensitive means of screening for gynecological pathology. MATERIALS AND METHODS: The records of 24 girls younger than 6 years who presented with vaginal discharge or bleeding were reviewed retrospectively. All patients were evaluated with noninvasive imaging, a pelvic examination while under anesthesia, vaginoscopy and cystoscopy. RESULTS: Noninvasive imaging was useful in identifying 5 of 7 vaginal foreign bodies. However, noninvasive imaging identified only 2 of 6 malignancies. These malignancies consisted of rhabdomyosarcoma (3 patients) and endodermal sinus tumor (3). Two girls also had benign vaginal mullerian papillomas that were not identified by noninvasive imaging. Noninvasive imaging did not aid in the diagnosis of sexual abuse. CONCLUSIONS: Based on these data, we recommend that all girls younger than 6 years who present with persistent vaginal discharge or bleeding be evaluated with pelvic examination while under anesthesia, to be followed by vaginoscopy and cystoscopy if no readily identifiable pathology is found by simple genital examination alone, regardless of the results of noninvasive imaging studies.

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.

Klippel-Trénaunay syndrome: 2 case reports and a review of genitourinary manifestations.

PURPOSE: We summarize the literature and present our experience with genitourinary manifestations of the Klippel-Trénaunay syndrome, which can lead to challenging management problems. MATERIALS AND METHODS: We report on 2 patients with genitourinary manifestations of the Klippel-Trénaunay syndrome and performed a MEDLINE review of the literature using the key words "Klippel-Trénaunay," "vascular malformation" and "genitourinary." RESULTS: Genitourinary manifestations were cited in 18 articles, including 1,174 cases of the Klippel-Trénaunay syndrome, detailing the presentation and management of bladder, external genitalia and retroperitoneal involvement in the Klippel-Trénaunay syndrome. The overall genitourinary symptoms in patients with the Klippel-Trénaunay syndrome seem to occur in the more severe cases and usually involve cutaneous vascular malformations of the trunk, pelvis and genitalia. CONCLUSIONS: Intra-abdominal and intrapelvic extension of the vascular malformations of the Klippel-Trénaunay syndrome frequently occurs concurrently with the lower abdominal, pelvic cutaneous involvement of the external genitalia, as in our 2 cases and in our review of the literature. These data provide a better understanding of the spectrum of genitourinary manifestations in the Klippel-Trénaunay syndrome and provide insight for the clinician to formulate individual therapies for these patients.

Long-term urological complications in survivors younger than 15 months of advanced stage abdominal neuroblastoma.

PURPOSE: We evaluated the long-term urological complications in survivors of infant advanced stage abdominal neuroblastoma. MATERIALS AND METHODS: The records of patients who presented during an 8-year period with surgical problems related to the kidney and who had survived advanced stage (IV and IV-S) neuroblastoma were reviewed. RESULTS: Of 7 patients identified 3 had complications of obstruction from retroperitoneal fibrosis and 4 had renal cell carcinoma. In the renal cell carcinoma group 3 patients had synchronous, multifocal, bilateral tumors and 1 had a tumor in a solitary kidney. Pathological examination of renal cell carcinoma revealed oncocytoidy with solid and papillary patterns. One patient underwent bilateral nephrectomy but in the remaining 3 renal preservation surgery was performed. All 7 patients have no progression of secondary complications 2 to 8 years after initial presentation. CONCLUSIONS: Survivors of advanced stage abdominal neuroblastoma may be predisposed to long-term urological complications well after initial diagnosis. Because of the risk of renal damage from obstruction secondary to retroperitoneal fibrosis, and the propensity to have renal cell carcinoma, close long-term followup using abdominal imaging is recommended.

Extraperitoneal placement of renal allografts in children weighing less than 15 kg.

PURPOSE: Extraperitoneal renal transplantation is not routine in small recipients, in whom transperitoneal engraftment is the norm. The outcome of extraperitoneal placement of renal allografts in children weighing less than 15 kg. was evaluated at 2 institutions. MATERIALS AND METHODS: We retrospectively reviewed all pediatric renal transplantations at 2 institutions from 1988 to 2000 and identified 29 children 14 to 72 months old (mean age 29.2) weighing less than 15 kg. (range 8 to 14.8, mean 11.2). All children underwent allograft placement extraperitoneally via a modified Gibson and low midline retroperitoneal incision in 27 and 2, respectively. A concurrent procedure was done via the same incision during 2 ipsilateral and 2 bilateral nephrectomies. RESULTS: Of the 29 patients 25 have a functioning renal allograft. In 2 cases the initial allograft was lost due to early postoperative thrombosis and acute rejection in 1 each. Two patients with a functioning allografts died of medical complications greater than 2 years after transplantation. One child required reexploration secondary to fascial dehiscence and an additional recipient required pyeloureterostomy due to ureteral necrosis after living related donor transplantation. CONCLUSIONS: Extraperitoneal renal transplantation is technically feasible in children who weigh less than 15 kg. This approach preserves the peritoneal cavity, limits potential gastrointestinal complications and allows the confinement of potential surgical complications, such as bleeding and urinary leakage. In addition, this approach provides complete access to the retroperitoneum to enable concurrent retroperitoneal surgery, such as nephrectomy, to be performed safely. We recommend that extraperitoneal renal engraftment should become routine in children weighing less than 15 kg. rather than using the more common transperitoneal approach for allograft placement.

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.

The undescended testicle.

The cryptorchid testis is a common pediatric condition, usually diagnosed by the primary physician. The diagnosis, classification, and treatment options of the cryptorchid testis are discussed in hopes of clarifying some of the controversy surrounding this common problem.

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.

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.

Bladder augmentation: does it predispose to prosthetic infection of simultaneously placed artificial genitourinary sphincters or in situ ventriculoperitoneal shunts?

OBJECTIVE: To review previous reports and our experience in assessing the risk of prosthetic infections in patients undergoing bladder augmentation simultaneously with artificial genitourinary sphincter (AGUS) implantation, and in patients with in situ ventriculoperitoneal (VP) shunts, implicated as a cause of shunt infection. PATIENTS AND METHODS: The literature was searched to identify the number of prosthetic infections (AGUS or VP shunt) reported in patients who have undergone bladder augmentation. Additionally, the records of 53 myelodysplastic patients at our institution who had undergone bladder augmentation were reviewed to determine the incidence of AGUS and/or VP shunt infections. An AGUS was placed in 17 of these patients, who were then divided into three groups based upon the timing of their AGUS placement relative to bladder augmentation. Of the 53 patients, 47 had an in situ VP shunt at the time of their augmentation. All patients were followed for at least 12 months. RESULTS: The reported rate of AGUS infection at the time of simultaneous bladder augmentation was not significantly different from that when these procedures were staged. In the present series, the AGUS became infected in two patients (12%); one infection occurred in each of 10 patients undergoing simultaneous procedures (10%) and one developed in each of the seven patients undergoing staged procedures (14%). Although VP shunt infections have been reported after bladder augmentation, none of the present patients had a VP shunt infection after bladder augmentation. CONCLUSION: These results suggest that bladder augmentation is not associated with an increased risk of prosthetic infection in patients undergoing simultaneous placement of an artificial sphincter or in those who have an in situ VP shunt.

Elevated bladder urine concentration of transforming growth factor-beta1 correlates with upper urinary tract obstruction in children.

PURPOSE: We evaluated urinary transforming growth factor-beta1 (TGF-beta1) concentration in children with upper urinary tract obstruction as a potential tool for supporting the diagnosis of clinically significant obstruction. MATERIALS AND METHODS: Renal pelvic and bladder urine samples were obtained for analysis from 30 patients a median of 5 months old who underwent surgery for obstruction at the ureteropelvic (29) and ureterovesical (1)junctions. Urinary TGF-beta1 concentration was measured using a quantitative sandwich enzyme-linked immunoassay technique. Bladder urine TGF-beta1 in patients with obstruction was compared with that in controls. In addition, we compared renal pelvic and bladder urine TGF-beta1 in patients with obstruction. RESULTS: Mean bladder urine TGF-beta1 plus or minus standard error of mean was 4-fold higher in patients with upper tract obstruction than in controls (195 +/- 29 versus 47 +/- 7 pg./mg. creatinine, p <0.001). In the obstructed group mean TGF-beta1 in the renal pelvic urine was 378 +/-86 pg./mg. creatinine, or twice that of the bladder urine (p = 0.02). CONCLUSIONS: Bladder urine TGF-beta1 in patients with upper urinary tract obstruction is significantly elevated compared with that in controls. To our knowledge our study is the first to identify a bladder urinary marker that correlates with upper urinary tract obstruction with greater than 90% sensitivity. Measuring TGF-beta1 in a voided bladder urine sample may provide an objective and noninvasive test for assisting in the diagnosis of upper urinary tract obstruction.

Multi-institutional study of testicular microlithiasis in childhood: a benign or premalignant condition?

PURPOSE: Testicular microlithiasis, a rare ultrasonographic diagnosis in children, has been shown to coexist in benign and malignant conditions. The natural history of incidentally discovered testicular microlithiasis has not been well defined in the pediatric population. The concern that testicular microlithiasis may be a premalignant condition has been raised. Reports indicate as much as a 45% association of germ cell tumors with testicular microlithiasis at the time of tumor diagnosis and there have been 4 cases of interval testicular tumor development associated with preexisting testicular microlithiasis. To address this issue we performed a multi-institutional study to evaluate children with incidentally diagnosed testicular microlithiasis. MATERIALS AND METHODS: Data on 26 patients with a mean age of 12.3 years at presentation with incidentally discovered testicular microlithiasis were collected from 7 institutions. Presenting scrotal conditions were reviewed. Two children with a previous testicular malignancy were excluded from study. RESULTS: Followup ranged from 1 month to 7 years (mean 27.6 months). Testicular biopsy and tumor marker (alpha-fetoprotein and beta-human chorionic gonadotropin) determinations were performed in 9 and 15 patients, respectively. To date no testicular tumor has developed during clinical followup. CONCLUSIONS: Our multi-institutional study has not yet shown a trend toward the malignant degeneration of incidentally diagnosed testicular microlithiasis in children. However, we still advocate close surveillance of patients with testicular microlithiasis, such as yearly testicular ultrasound, physical examination, and judicious tumor marker determinations. We propose that a registry be started to follow prospectively patients with testicular microlithiasis to define its significance better.

The prune-belly syndrome: a new and simplified technique of abdominal wall reconstruction.

PURPOSE: Various techniques of reconstruction have been developed to improve the cosmetic and functional status of the abdominal wall in the prune-belly syndrome. We describe a new extraperitoneal plication technique of abdominoplasty that is simplified in comparison to other established procedures in that it obviates the need for a fascial incision and/or entrance into the peritoneal cavity in patients who do not require a concurrent intra-abdominal procedure. MATERIALS AND METHODS: Since 1980 this technique of abdominoplasty has been performed in 13 patients 9 months to 11 years old (mean age 3.8) at 2 institutions. Seven patients underwent surgery before age 2.5 years. Abdominal wall reconstruction was performed as an isolated extraperitoneal procedure in 5 patients, while 8 had concomitant procedures performed with the abdominoplasty, including bilateral Fowler-Stephens orchiopexy in 7, ureteral reconstruction/reimplantation in 5, excision of urachal diverticulum or cyst in 2, reduction cystoplasty in 1 and Tenckhoff catheter placement in 1. RESULTS: In all cases the cosmetic result was excellent and satisfactory to patients, parents and surgeons. Since the first procedure was performed 17 years ago, only 1 patient has returned with abdominal wall laxity or bulging in the area of repair. CONCLUSIONS: Our method of abdominal wall reconstruction in the prune-belly syndrome produces a cosmetically excellent and durable result. In contrast to other techniques of abdominoplasty, the need for a fascial incision and/or entrance into the peritoneal cavity is avoided. We believe that this modified procedure offers distinct technical and anatomical advantages over other existing techniques.

Reproductive understanding, sexual functioning and testosterone levels in men with spina bifida.

PURPOSE: We assessed the sexual functioning and understanding in men with myelodysplasia. MATERIALS AND METHODS: Of the 378 patients with myelodysplasia followed at our multidisciplinary clinic 170 are adults, including 58 men older than 18 years. A total of 57 men was available for interview. A questionnaire was administered to determine patient educational level, sexual understanding, sexual function and marital status, and serum testosterone levels were measured. RESULTS: The majority of the patients learned about sexual reproduction from school classes with 48 (84%) having achieved a twelfth grade education or higher. A total of 41 patients (72%) accurately described the basic concepts of reproductive physiology. Penile erections were experienced by 41 men (72%) including 27 (66%) who ejaculated with erection. Three patients ejaculated without erection. Sexual intercourse was attempted by 20 men (35%). Of the 11 patients (19%) who attempted to father children 8 (14%) were successful. Twelve patients (21%) have been married, including 2 who are divorced. Serum testosterone levels in 44 patients were normally distributed. CONCLUSIONS: Sexual reproductive understanding, and erectile and ejaculatory function are present in many men with myelodysplasia. The level of the neurological lesion was not predictive of erectile or ejaculatory function but it appears that reproductive potential is favored by lower and less severe lesions. All but 1 of the 8 patients who fathered children had an L5 or sacral neurological level lesion, each was ambulatory and none had a ventriculoperitoneal shunt at the time of conception. These data may prove useful when counseling patients and their parents about eventual sexual performance.