Mutant fibroblast growth factor receptor 3 induces intracellular signaling and cellular transformation in a cell type- and mutation-specific manner.

Although activating mutations of fibroblast growth factor receptor 3 (FGFR3) are frequent in bladder tumors, little information is available on their specific effects in urothelial cells or the basis for the observed mutation spectrum. We investigated the phenotypic and signaling consequences of three FGFR3 mutations (S249C, Y375C, and K652E) in immortalized normal human urothelial cells (TERT-NHUC) and mouse fibroblasts (NIH-3T3). In TERT-NHUC, all mutant forms of FGFR3 induced phosphorylation of FRS2alpha and ERK1/2, but not AKT or SRC. PLCgamma1 phosphorylation was only observed in TERT-NHUC expressing the common S249C and Y375C mutations, and not the rare K652E mutation. Cells expressing S249C and Y375C FGFR3 displayed an increased saturation density, related to increased proliferation and viability. This effect was significantly dependent on PLCgamma1 signaling and undetectable in cells expressing K652E FGFR3, which failed to phosphorylate PLCgamma1. In contrast to TERT-NHUC, expression of mutant FGFR3 in NIH-3T3 resulted in phosphorylation of Src and Akt. In addition, all forms of mutant FGFR3 were able to phosphorylate Plcgamma1 and induce morphological transformation, cell proliferation, and anchorage-independent growth. Our results indicate that the effects of mutant FGFR3 are both cell type specific and mutation specific. Mutant FGFR3 may confer a selective advantage in the urothelium by overcoming normal contact inhibition of proliferation.

Ultrasound assessment of caudal catheter position in infants.

The positioning of caudally inserted epidural catheters is crucial to their effectiveness. However, level assessment can be difficult and time consuming. We report the use of ultrasound to assess the catheter position in three patients aged between 1 and 10 months. The advantages and disadvantages of this technique are discussed in relation to other methods of assessing caudal catheter placement.

Long-term evaluation of metabolic profile and bone mineral density after ileocystoplasty in children.

PURPOSE: We evaluated the long-term effects of ileocystoplasty on linear growth, serum electrolytes, acid-base profile and bone mineral density (BMD) in a group of neurologically intact children with a mean followup of 8.9 years. MATERIALS AND METHODS: Between 1988 and 1997, 9 girls and 16 boys with a mean age of 6 years (range 1 month to 14 years) underwent ileocystoplasty for etiologies other than myelomeningocele and neuropathic bladder. Indications for ileocystoplasty were small noncompliant bladder secondary to bladder exstrophy in 12 cases, bladder outlet obstruction in 10 and post-partial cystectomy for rhabdomyosarcoma in 3. All patients underwent clinical evaluation, supine height measurement, serum electrolytes, arterial blood gases and BMD measurement using a fan beam dual energy absorpitometry scan. BMD was measured at L1-L4 and corrected for age and sex. RESULTS: Followup ranged from 4 to 13 years (mean 8.9). Serum creatinine was normal in 20 of the 25 patients. All patients had normal supine height measurement with a mean of 45th (+/- 9) centile on growth charts. Serum electrolytes, calcium, phosphorus and arterial blood gases were normal in all patients. Mean BMD corrected for age and sex was 89 (+/- 10)%. BMD was normal in 17 of 25 (68%) patients. Mild reduction in bone density between 1 and 2 standard deviations below the age/sex mean was documented in 3 (12%) patients and the remaining 5 (20%) showed marked osteopenia of 2 or more standard deviations. Of the latter 5 patients 2 had increased serum creatinine, 1 had a history of radiotherapy for pelvic rhabdomyosarcoma and 2 had cloacal exstrophy and short bowel, all of which might have contributed to the osteopenia. CONCLUSIONS: Ileocystoplasty for children with normal kidney function is not associated with alterations in serum electrolytes or arterial blood gases in the long term. However, 32% of patients showed variable degrees of reduction in BMD. Although marked reduction in BMD was associated with cofactors, 12% of patients had evidence of mild osteopenia in absence of those cofactors. We recommend routine preoperative and longitudinal followup BMD measurements for children undergoing intestinal bladder augmentation.

Post-chemotherapy microscopic residual prostate rhabdomyosarcoma: long-term conservative follow-up.

In spite of advances in the treatment of childhood bladder and prostate rhabdomyosarcoma (RMS), the ability to detect minimal residual disease correlates imperfectly with the ultimate outcome. We report the long-term follow-up of a child with microscopic residual RMS after chemotherapy. The correct interpretation of the histologic findings spared the child unnecessary additional therapy and raises enigmatic questions about the biology of minimal residual disease.

[Bladder hemangioma: a rare cause of hematuria. Apropos of a case. Review of the literature]. / L'hémangiome vésical: une cause rare d'hématurie. A propos d'une observation. Revue de la littérature.

The authors report a clinical case of multiple vesical haemangioma, a rare congenital benign vascular tumour essentially affecting children and young adults. These tumours may be solitary or multiple, and essentially spread to the bladder wall. They are sometimes associated with other sites, such as in the rare Klippel-Trenaunay-Weber syndrome. Usually presenting in the form of macroscopic haematuria, they are essentially diagnosed by endoscopy. Depending on the case, treatment consists of partial cystectomy or laser photocoagulation, rather than endoscopic resection, which is haemorrhagic and incomplete, or radiotherapy, which is insufficient. Selective arterial embolization is rarely used.

Congenital genitourinary hemangiomas in a patient with the Klippel-Trenaunay syndrome: management with the neodymium:YAG laser.

The Klippel-Trenaunay syndrome is an unusual congenital anomaly characterized by cutaneous hemangiomas, multiple varicosities, soft tissue hypertrophy and, rarely, gastrointestinal or genitourinary hemangiomas. The large bladder as well as multiple penile hemangiomas in our patient were treated successfully with the neodymium:YAG laser with minimal morbidity.

[Rhabdomyosarcomas discovered in newborn infants. Study of markers of muscle differentiation]. / Rhabdomyosarcomes de découverte néonatale. Etude des marqueurs de différenciation musculaire.

Rhabdomyosarcomas were observed at birth in two premature infants. The evolution of these tumors was both rapid and fatal. One case was a botryoid sarcoma of the bladder and the second was a cervical alveolar sarcoma of Riopelle and Thériault. A cytological differentiation of the tumor was observed in the first case spontaneously and in the second following chemotherapy. In the second case histology, immunocytochemistry and a novel biochemical analysis of the contractile proteins demonstrated this differentiation of the tumor. The cellular reactivity varies according to the degree of muscular differentiation that can be defined either by studying the type of intermediate filaments present or the expression of specific muscle contractile proteins.

Congenital disseminated neurofibromatosis: a "benign" diagnosis with malignant prognosis.

A neonate with congenital disseminated neurofibromatosis involving skin, subcutaneous tissues retropharyngeal, retroperitoneal and urinary bladder is presented. The massive presentation precluded radical surgical approach. This seems to be the first report of congenital widely disseminated neonatal neurofibromatosis in the English literature.

Hemangiolymphangioma of the urinary bladder in a child.

A rare case of hemangiolymphangioma of the urinary bladder with associated cutaneous hemangiomas of the shaft and glans penis and the scrotum is presented. Unusual features of clinical presentation, noninvasive diagnosis, and the surgical management are discussed.

Bilateral cystic nephroblastomas and botryoid sarcoma in a child with Dandy-Walker syndrome.

We report an autopsy case of an 8-month-old male infant with bilateral cystic nephroblastomas, a botryoid sarcoma involving the urinary bladder, microencephaly, the Dandy-Walker syndrome, bilateral cataracts, hypospadias, and male pseudohermaphroditism. An unusual combination of congenital malformation and tumors may reflect the presence of a mutant gene.