A Paratesticular Serous Borderline Tumor in a Pediatric Patient With Proteus Syndrome.

Proteus syndrome is a rare disorder of asymmetric overgrowth of various tissues of the body and is associated with specific tumors appearing before the second decade. Although there have been reports of lesions of the genitourinary tract associated with Proteus syndrome, a case of serous borderline tumor of the paratestis has not been previously recorded. We report the first such case in a 20-month-old child who presented with a left-sided testicular mass that was found on histology to be a serous borderline tumor of the paratestis. Surgical management included a left inguinal radical orchiectomy and surveillance follow-up.

Staging paratesticular rhabdomyosarcoma in the "as low as reasonably achievable" age: the case for PET-CT.

Rhabdomyosarcoma accounts for 40% of paratesticular malignancies and 5% of testicular and paratesticular malignancies in children and adolescents. The Children's Oncology Group currently recommends computed tomography (CT) or magnetic resonance imaging for staging of paratesticular rhabdomyosarcoma in children. The present case illustrates a 9-year-old boy with paratesticular rhabdomyosarcoma who had negative findings on a staging CT scan and a subsequent positron emission tomography-CT scan demonstrating retroperitoneal lymph node metastasis. In the era of "as low as reasonably achievable" imaging, positron emission tomography-CT should be considered first-line imaging for staging to improve the sensitivity and specificity of staging for paratesticular rhabdomyosarcoma.

Molecularly confirmed primary malignant rhabdoid tumor of the urinary bladder: implications of accurate diagnosis.

Malignant rhabdoid tumors (MRTs) are well recognized in the kidney and extrarenal sites such as soft tissues, retroperitoneum, and bladder but are classified as atypical teratoid/rhabdoid tumors in the central nervous system. The unifying features of both extracranial MRT and atypical teratoid/rhabdoid tumors are the exon deletions/mutations of the SMARCB1 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily b, member 1) gene in 22q11.23 and resulting loss of SMARCB1/INI1 (integrase interactor 1) protein expression by immunohistochemistry. We herein report a case of extrarenal rhabdoid tumor confined to the bladder in a 3-year-old child, diagnosed by histopathology and confirmed by immunohistochemical and molecular studies. This is only the fourth molecularly proven primary MRT of the bladder to be reported. The patient's peripheral blood was negative for the deletions observed in the tumor, thereby confirming a sporadic origin for the tumor. Given the possible dismal outcome, urgency for definitive diagnosis to institute intensive multimodality therapy, histopathologic differential diagnosis with rhabdomyosarcoma and urothelial carcinoma with rhabdoid features, and lack of consensus management guidelines, oncologists, urologists, and pathologists must be aware of this entity. Evaluation for a germ line SMARCB1 alteration may greatly aid risk stratification and family planning.

Stromal hyperplasia in male bladders upon loss of transforming growth factor-beta signaling in fibroblasts.

PURPOSE: Rapid bladder growth associated, partial urethral obstruction and embryonic bladder development entail stromal-epithelial interactions involving signaling by the cytokine transforming growth factor-beta (TGF-beta). However, to our knowledge the role of TGF-beta in bladder stromal hyperplasia and hypertrophy is not understood. MATERIALS AND METHODS: In an effort to understand the specific role of TGF-beta signaling in bladder stroma a fibroblast specific conditional knockout mouse of the type II TGF-beta receptor gene, Tgfbr2(/spko), was generated using Cre-lox methodology. Bladders from 18, 7 to 8-week-old mice were harvested for histological and immunohistochemical analysis. RESULTS: Bladders from homozygous Tgfbr2(/spko), male mice showed marked hypertrophy in the lamina propria and smooth muscle layers in the absence of visible or functional bladder obstruction by age 8 weeks. However, age matched female mice of the same genotype maintained bladder architecture similar to that in wild-type littermate male and female controls. Immunohistochemistry for the phosphorylated form of Smad2 indicated a general loss in TGF-beta signaling in the lamina propria of bladders of male and female Tgfbr2(/spko), mice, and yet pronounced alpha-smooth muscle actin expression was noted in male Tgfbr2(/spko), bladders, which is a marker for myofibroblasts. CONCLUSIONS: A sex disparity was observed in the Tgfbr2(/spko), mouse model lacking TGF-beta signaling in fibroblasts. Deletion of TGF-beta in males leads to a hypertrophied lamina propria and muscularis externa with myofibroblast differentiation and proliferation. Female homozygous Tgfbr2(/spko), bladders appeared the same as those of wild-type male and female controls. This model suggests a role for stromal TGF-beta signaling with estrogens and androgens in bladder fibrosis.

Pediatric ureteroscopic stone management.

PURPOSE: We reviewed our experience of 5 years using ureteroscopy with laser lithotripsy to treat stone disease in prepubertal children. MATERIALS AND METHODS: A retrospective review was performed of all ureteroscopic procedures performed in prepubertal children. RESULTS: A total of 33 ureteroscopic procedures were performed in 29 prepubertal children (15 males and 14 females) 5 to 144 months old (mean age 94 months, including 3 patients 24 months or younger). Stones were located in the renal pelvis in 1 case (3%), proximal ureter in 3 (9%), mid ureter in 5 (15%) and distal ureter in 24 (73%). Stone size ranged from 3 to 14 mm (mean 6). Eight patients required balloon dilation of the ureteral orifice. Followup ranged from 1 to 66 months (mean 11). Stone-free rate after initial ureteroscopy and laser lithotripsy was 88%, with all distal and mid ureteral stones (3 to 9 mm, mean 5) successfully treated. Three patients with proximal ureteral stones 7 to 14 mm in diameter (mean 10.3) required a secondary procedure (repeat ureteroscopy in 2 and shock wave lithotripsy in 1) to become stone-free. One patient with cystinuria and a renal pelvic stone measuring 14 mm required shock wave lithotripsy and percutaneous nephrostolithotomy. There were no major complications of ureteroscopy but there was 1 case of extravasation at the ureterovesical junction after balloon dilation that was managed with stent placement. CONCLUSIONS: Although more patients and longer followup are needed, ureteroscopy with laser lithotripsy is an excellent first line treatment for children with stones in whom conservative therapy fails, especially those with distal and mid ureteral stones. Patients with a stone burden of 10 mm or greater, especially in the proximal ureter, likely will require a secondary procedure to become stone-free.

Primary bladder neck dysfunction in children and adolescents II: results of treatment with alpha-adrenergic antagonists.

PURPOSE: Little has been reported on the occurrence of primary bladder neck dysfunction (PBND) in the pediatric patient, particularly as it relates to the use of alpha-blocker therapy, the mainstay of medical therapy in adults. Diagnosed on videourodynamics (VUDS), PBND is characterized by the constellation of prolonged opening time, incomplete bladder neck funneling, quiet pelvic floor electromyogram (EMG) during voiding and abnormal pressure flow parameters. We report the VUDS findings in PBND and our experience with alpha-blocker therapy in the pediatric and adolescent population. MATERIALS AND METHODS: A total of 34 symptomatic patients met all VUDS criteria for PBND, and alpha-blocker therapy was initiated in 26. All patients were monitored with serial noninvasive uroflow studies with pelvic floor EMG (uroflow/EMG) before and after initiation of alpha-blocker therapy. Objective clinical response was assessed by measuring average and maximum uroflow rates, post-void residual urine volumes and pelvic floor EMG lag time, a correlate of opening time. RESULTS: A total of 26 patients with PBND (20 males, 6 females) 5.5 to 20 years old at initiation of therapy (mean age 12.8 years) were treated with alpha-blockers. Mean average and maximum uroflow rates improved from 5.5 to 12.6 cc per second and from 10.3 to 19.7 cc per second, respectively, while mean EMG lag time decreased from 24.4 to 5.7 seconds and post-void residual urine volume from 98.9 to 8.9 cc (all p <0.001). Mean followup was 31 months, with all patients reporting significant symptomatic improvement. No patient experienced any major adverse side effects. The 8 patients with PBND who refused alpha-blocker therapy had no improvement symptomatically or urodynamically with time, and those who discontinued therapy had a return to pretreatment values. CONCLUSIONS: PBND is an often overlooked but significant cause of voiding dysfunction in children and adolescents. In our experience alpha-blockers are clinically effective therapy for PBND and have been reasonably well tolerated in our young patients for what may possibly be a lifelong problem.

When can persistent hydroureteronephrosis in posterior urethral valve disease be considered residual stretching?

PURPOSE: Persistent hydroureteronephrosis (HUN) is often seen in boys with a history of a posterior urethral valve even years after valve ablation and it is often assumed to represent residual stretching. We determined the association of HUN with urodynamic abnormalities, the effect on HUN of treating these abnormalities and when persistent HUN could be considered residual stretching. MATERIALS AND METHODS: Of 71 patients with a posterior urethral valve evaluated after valve ablation 20 (28.2%) had persistent HUN in a total of 32 renal units (RUs). The degree of HUN was graded as mild, moderate or severe. Videourodynamics were performed in all patients with persistent HUN and abnormal urodynamic findings were aggressively treated. HUN was then reassessed and categorized as resolved, improved or unchanged. RESULTS: Abnormal urodynamic findings, primarily hypocompliance and instability, were noted in all 20 patients with HUN. All patients compliant with treatment showed dramatic improvement or complete resolution of abnormal urodynamic parameters. The 32 RUs with persistent HUN were initially graded as mild (8), moderate (13) and severe (11). HUN resolved in 15 RUs and improved to a lower grade in 11 in 26 of the 27 RUs (96.3%) in the 17 patients compliant with treatment. The 3 boys (5 RUs) who were noncompliant with treatment had neither decreased HUN nor improved urodynamic parameters. The 12 of 27 RUs (44.4%) in the treatment group in which HUN failed to resolve completely had no distal ureteral obstruction or identifiable persistent urodynamic abnormality and, thus, they can be labeled as having residual stretching. CONCLUSIONS: Persistent HUN following valve ablation should not be considered residual dilatation until a thorough urodynamic evaluation has been done and any abnormal parameters are addressed. With correction of these abnormal parameters one can expect significant lessening of HUN and hopefully improved long-term preservation of renal function.

Myogenic failure in posterior urethral valve disease: real or imagined?

PURPOSE: It has been suggested that hypocontractility or myogenic failure develops in older boys with a history of 9 posterior urethral valved as the hyperactive, poorly compliant bladders decompensate with age. Also a much higher prevalence of myogenic failure has been reported than we have observed. We determine the prevalence of myogenic failure in boys with a posterior urethral valve and whether myogenic failure was a consequence of earlier detrusor instability or diminished compliance. MATERIALS AND METHODS: We retrospectively reviewed the urodynamic findings of 51 boys after transurethral ablation of a posterior urethral valve. Group 1 (longitudinal group) consisted of 11 boys 12 to 19 years old who had undergone at least 1 serial urodynamic study before and 1 after age 10 years. Group 2 (younger group) included 33 boys whose urodynamic testing was performed before age 10 years. Group 3 (older group) comprised 7 previously treated boys whose initial urodynamic study was done after age 12 years. RESULTS: Overall, myogenic failure was noted in 3 (all group 1) of 51 (5.9%) patients. Each of the 3 boys initially had a hypocompliant bladder, and myogenic failure developed only after institution of anticholinergic therapy and resolved once anticholinergics were discontinued. An additional 34 boys treated with anticholinergics did not have myogenic failure. No tendency towards myogenic failure or marked increase in bladder capacity for age was noted in the older boys. CONCLUSIONS: In our experience myogenic failure is uncommon and more likely secondary to anticholinergic therapy than a preordained consequence of valve disease. We postulate that our proactive, early aggressive use of urodynamic studies and pharmacotherapy to identify and manage the secondary effects of valve disease reduces the incidence of myogenic failure.