S. Glüer

Etiologic classification of severe hypospadias: Implications for prognosis and management

Objective Classification of severe hypospadias employing a broad array of diagnostic tools. Standardization of a diagnostic approach to children with hypospadias. Identification of patients at risk of having malignancies and endocrine problems. Design Retrospective analysis of patients in a single-center study. Subjects Thirty-three patients with severe (scrotal or penoscrotal) hypospadias, aged 1 to 18 years. Methods Clinical assessment, ultrasonography, karyotyping, endocrine evaluation including adrenal steroid concentrations, sex hormone-binding globulin test for androgen sensitivity, human chorionic gonadotropin stimulation with determination of testosterone and dihydrotestosterone concentrations to exclude 5α-reductase deficiency, and molecular genetic analysis of the androgen receptor gene and the 5α-reductase gene. Results In 12 patients the cause was clarified. Diagnoses included Drash syndrome with Wilms tumor in infancy (3 patients), partial androgen msensitivity resulting from androgen receptor mutations (2), true hermaphroditism (2), chromosomal aberration (1), deficiency of antimullerian hormone (1), gonadal dysgenesis (1), partial 5α-reductase deficiency caused by a novel point mutation (1), and XX-male syndrome (1). Twelve patients had associated findings such as cardiac malformations (3 patients), rectal atresia (1), dilation of urinary tract (2), cystinuria (1), and others. Conclusions Patients with severe hypospadias should be submitted to a standardized set of diagnostic procedures in infancy. A stepwise diagnostic study avoids unnecessary, invasive, and expensive testing. A high proportion of classified causes can be expected. Patients at risk of having malignancies or hormonal disorders must remain under close surveillance.

Stem-like Cells in Human Hepatoblastoma

Hepatoblastoma is a pediatric liver tumor with epithelial components resembling embryonal and fetal liver cells. The existence of teratoid hepatoblastoma suggests the presence of stem cells in hepatoblastoma. The aim of this study was to analyze the expression of stem cell markers in hepatoblastomas. We studied specimens from 10 hepatoblastomas. Five of the hepatoblastomas were of epithelial and five of mixed type. Immunohistochemistry (IHC) for the stem cell markers CD34, Thy1, c-kit, and the hepatic or biliary lineage markers CK-18, OCH, CK-7, and CD56 was performed. Double IHC for stem cell and lineage markers was used to identify putative liver stem cells. The different markers showed distinct distributions on the tumor cells. Cells in atypical ducts were found to express simultaneously stem cell markers and hepatocytic or biliary lineage markers. Other cells in connective tissue showed c-kit expression, but not hepatic or biliary marker expression. The data show the presence of different cell populations bearing stem cell markers in human hepatoblastoma. Ductal cells co-expressing stem cell markers and hepatic lineage markers phenotypically resemble hepatic stem-like cells. These findings support the thesis that stem cells play a role in the histogenesis of hepatoblastoma.

Hepatocyte growth-factor-scatter factor can stimulate post-operative tumor-cell proliferation in childhood hepatoblastoma.

Rapid growth of residual tumor after partial hepatectomy has been observed during the period of liver regeneration in children with malignant embryonal hepatoblastoma. The aim of this study was to elucidate the role of hepatocyte growth‐factor‐scatter factor (HGF‐SF) in this phenomenon. Markedly increased serum levels of HGF‐SF up to 15 ng/ml were found in 13/18 patients after liver resection and in 6/16 patients with regressive tumors after chemotherapy, in comparison with 15 patients with non‐pre‐treated hepatoblastoma and 20 healthy children of the same age group. In the tumors, epithelial tumor cells highly expressed the HGF‐SF receptor c‐met, as shown by immunohistochemistry and m‐RNA RT‐PCR. The hepatoblastoma cell lines HepT1, HepT3 and HUH6 reacted with significantly increased proliferation to rhHGF‐SF in these concentrations (1‐15 ng/ml). In the tumors, HGF‐SF was found to be expressed in the stromal fibroblasts. In culture, hepatoblastoma cells (HepT3, HUH6) stimulated secretion of the factor by human fibroblasts, indicating the paracrine fashion of intratumoral HGF‐SF production. Cultured hepatoblastoma cells ceased to proliferate at 20‐50 ng/ml HGF‐SF, and they underwent cell death at ≥100 ng/ml. In contrast, the hepatocellular‐carcinoma cell line HepG2 decreased growth under HGF‐SF in a dose‐dependent manner. We conclude that post‐operatively secreted and intratumorally produced HGF‐SF can function as a growth factor for hepatoblastoma, while the same agent has a cytostatic effect in unphysiologically high concentrations. Int. J. Cancer 85:151–159, 2000. ©2000 Wiley‐Liss, Inc.

Polysialylated Neural Cell Adhesion Molecule in Childhood Rhabdomyosarcoma

Rhabdomyosarcoma (RMS) cells express the polysialylated (PSA) form of the neural cell adhesion molecule (NCAM). During embryogenesis, PSA-NCAM is widespread and dynamically regulates embryonal developing processes, whereas postnatally, PSA-NCAM becomes restricted to a few regions of neural plasticity and regenerating neural tissues. Recently, PSA-NCAM has been shown to be a diagnostic and prognostic marker in adult patients with small cell lung cancer and multiple myeloma, both PSA-NCAM-expressing tumors. In this study, we determined the amount of PSA-NCAM in tumor specimens of nine children with different histologic types and clinical stages of RMS immunohistochemically, using the polysialic acid-specific MAb 735. In seven children, serum levels were investigated by an immunoluminescence assay using the same MAb. Patients with extensive disease showed strong staining of the tumor specimens, whereas patients with limited stages or after chemotherapy had distinctly a lesser amount of PSA-NCAM or almost no staining. Simultaneously, the serum levels were very high (up to 9-fold) in patients with extensive disease, whereas patients with limited disease or after successful therapy had normal serum levels. We conclude that PSA-NCAM expression is high in tumor specimens and serum of patients with advanced stages of RMS and decreases during successful therapy. PSA-NCAM might therefore serve as a marker for diagnosis and monitoring childhood RMS.

Serum polysialylated neural cell adhesion molecule in childhood neuroblastoma.

Neuroblastoma cells express the polysialylated form of the neural cell adhesion molecule (NCAM), which normally becomes restricted to a few neural tissues after embryogenesis. In this study, we investigated serum levels of polysialylated NCAM in 14 children with different grades and stages of neuroblastoma using an immunoluminescence assay, and compared the results to 269 healthy control subjects. Simultaneously, the polysialylated NCAM content of the tumours was determined by immunohistochemistry. Serum levels were dramatically elevated (more than sixfold) in children with advanced stages and fatal courses of disease, whereas children with differentiated tumour types and limited disease had low or normal levels. Serum concentrations correlated with the polysialylated NCAM content of the tumours, and they decreased during successful therapy. We therefore suggest polysialylated NCAM to be a useful marker monitoring childhood neuroblastoma.

Diagnosis and current management of penile agenesis.

Penile agenesis is a rare congenital anomaly in which early gender reassignment is recommended. In the past, multiple operations were carried out to form feminized external genitalia. The authors performed a definite genital reconstruction in a neonate using the posterior sagittal approach. Preoperatively, a magnetic resonance imaging (MRI) scan demonstrated erectile tissue, which was preserved and incorporated into the genital plasty. The operation included bilateral orchiectomy, urethral reconstruction, sigmoid vaginal replacement, and formation of the labia. The authors discuss the controversy around gender assessment. They emphasize the urethral hypotrophy to be a main challenge in this anomaly and conclude that immediate complete reconstruction is possible and should be performed in patients with this delicate condition.

Polysialylated neural cell adhesion molecule in childhood ganglioneuroma and neuroblastoma of different histological grade and clinical stage

Background and aims: Neuroblastoma cells express the polysialylated form of the neural cell adhesion molecule (PSA-NCAM), which normally becomes restricted to a few neural regions after embryogenesis. The aim of the present study was to evaluate PSA-NCAM as a marker in childhood neuroblastoma. Patients/methods: We studied the expression of PSA-NCAM on tumor specimens and in sera of 27 children, altogether, with ganglioneuroma and neuroblastoma of different histological grades and clinical stages. For both methods, immunohistochemistry on 5-μm frozen sections and immunoluminescence serum assay, the polysialic-acid-specific monoclonal antibody 735 was used. Results: PSA-NCAM expression was highest in patients with undifferentiated neuroblastoma and advanced stages of disease, whereas children with differentiated tumor types and low clinical stages had distinctly reduced or no reactivity in immunohistochemistry and, simultaneously, normal serum levels. PSA-NCAM expression correlated with other prognostic and diagnostic markers, such as MYCN gene amplification, and serum concentrations decreased during successful treatment. Conclusions: We conclude that PSA-NCAM, both immunohistochemically and in the serum, is a promising candidate for another useful diagnostic and prognostic tumor marker in childhood neuroblastoma.

Spontaneous neonatal pneumomediastinum: the "spinnaker sail" sign.

Spontaneous pneumomediastinum is a rare condition in the newborn, not associated with identifiable trauma or mechanical ventilation. It is diagnosed by a combination of physical examination and confirmatory chest radiograph, with various recognized signs identifiable in this condition. We report the case of a male neonate, who had pneumomediastinum confirmed by the presence of a wind blown spinnaker sail sign and was managed conservatively. We also reviewed the literature.

Excision of the Dilated Pelvis is not Necessary in Laparoscopic Dismembered Pyeloplasty

PURPOSE The surgical treatment of choice for significant hydronephrosis is dismembered pyeloplasty. While in open surgery, extensive resection of the dilated pelvis is common practice, laparoscopically usually only a sparing resection is performed. We compared the treatment results of both techniques to investigate whether extensive resection is necessary or not in dismembered pyeloplasty procedures. METHODS To obtain comparable renal units, matched pairs according to age and relative kidney uptake as shown by (123)J-orthoiodohippurate renography were selected out of a total of 76 patients who underwent dismembered pyeloplasty between 2000 and 2007. Twenty-four patients complied with the criteria for inclusion in the study. Changes in urinary drainage preoperatively and at three months postoperatively were compared between both groups. RESULTS The mean age in the sparing resection group was 3.8 years (range 0.3 to 14 years); in the extensive resection group it was 3.4 years (range 0.5 to 10 years). Mean urinary drainage improved significantly in both groups from 35.1 +/- 10.7 % to 75.2 +/- 13.2 % (sparing resection) vs. 45.1 +/- 23.7 % to 70.2 +/- 22 % (extensive resection). There were no differences between the groups (p > 0.05). CONCLUSIONS We conclude that extensive resection of the renal pelvis is not necessary in dismembered pyeloplasty procedures since there were no differences in the renographic outcome of comparable patients treated by the different surgical methods.

Benign papilloma of the cervix in childhood : immunohistochemical findings and review of the literature

Abstract Papillomas of the genital region are rare benign tumours causing sanguineous vaginal discharge in prepubertal girls. We report on a papilloma of the cervix in a 2-year-old girl. We characterize the tumour immunohistochemically and give a brief review about the current literature. Conclusion Genital tract papillomas are benign differ entiated tumours of probable Müllerian origin with a good prognosis even after tumour recurrence. Local excision is adequate for treatment.