Neuroblastoma is the most common extracranial solid tumor in childhood accounting for 8–10% of all childhood malignancies. The tumor is characterized by a spectrum of histopathologic features and a heterogeneous clinical phenotype. Modern multimodality therapy results in variable clinical response ranging from cure in localized tumors to limited response in aggressive metastatic disease. Accurate clinical staging and risk assessment based on clinical, surgical, biologic and pathologic criteria are of pivotal importance in assigning prognosis and planning effective treatment approaches. Numerous studies have analyzed the presence of several clinicopathologic and biologic factors in association with the patient's prognosis and outcome. Although patient's age, tumor stage, histopathologic classification, and MYCN amplification are the most commonly validated prognostic markers, several new gene mutations have been identified in sporadic and familial neuroblastoma cases that show association with an adverse outcome. Novel molecular studies have also added data on chromosomal segmental aberrations in MYCN nonamplified tumors. In this review, we provide an updated summary of the clinical, serologic and genetic prognostic indicators in neuroblastoma including classic factors that have consistently played a role in risk stratification of patients as well as newly discovered biomarkers that may show a potential significance in patients' management.
The Hippo pathway is an important signaling pathway that controls cell proliferation and apoptosis. It is evolutionarily conserved in mammals and is stimulated by cell–cell contact, inhibiting cell proliferation in response to increased cell density. During early embryonic development, the Hippo signaling pathway regulates organ development and size, and its functions result in the coordinated balance between proliferation, apoptosis, and differentiation. Its principal effectors, YAP and TAZ, regulate signaling by the embryonic stem cells and determine cell fate and histogenesis. Dysfunction of this pathway contributes to cancer development in adults and children. Emerging studies have shed light on the upregulation of Hippo pathway members in several pediatric cancers and may offer prognostic information on rhabdomyosarcoma, osteosarcoma, Wilms tumor, neuroblastoma, medulloblastoma, and other brain gliomas. We review the results of such published studies and highlight the potential clinical application of this pathway in pediatric oncologic and pathologic studies. These studies support targeting this pathway as a novel treatment strategy.
1 November 2000 in The American Journal of Tropical Medicine and Hygiene
Antimicrobial sensitivity tests were performed on four-hundred and ninety-seven bacterial isolates from Sudanese patients with diarrhea or urinary tract infections. Shigella dysenteriae type I and enteropathogenic Escherichia coli showed high resistance rates (percentage of isolates showing antibiotic resistance) against the commonly-used antimicrobial agents: ampicillin, amoxicillin, chloramphenicol, tetracycline, cotrimoxazole, nalidixic acid, sulfonamide, and neomycin, and were completely sensitive to ciprofloxacin. Eighteen resistance patterns against nine antimicrobial agents tested were observed in enteric pathogens. Resistance to ampicillin, amoxicillin, tetracycline, cotrimoxazole, and sulfonamide was the most frequent pattern. The common urinary pathogens, E. coli, Klebsiella pneumoniae, and Proteus mirabilis showed high rates of resistance to ampicillin, amoxicillin, cotrimoxazole, tetracycline, sulfonamide, trimethoprim, streptomycin, and carbenicillin. We recommend that physicians seek updated knowledge of the common antibiotic-sensitivity patterns when starting empirical antibiotic therapy in Sudanese patients with diarrhea or urinary tract infection.
Leydig cell tumors in children are rare, comprising only 4% to 9% of all primary testis tumors in prepubertal males. Almost all of these boys present with isosexual precocious pseudopuberty associated with increased testosterone, low gonadotropin levels and a testis mass. We present our experience with testis sparing enucleation of Leydig cell tumor in prepubertal boys. Two patients presented with isosexual precocious puberty at ages 6 and 9 years. Each patient had a well circumscribed, painless testicular mass, increased serum testosterone (101 and 444 ng/dl [normal 0 to 25]), normal gonadotropins and negative alpha-fetoprotein levels. Both patients underwent successful enucleation of the testis mass following proper testis oncological surgical principles. Both patients had normalization of the serum testosterone following enucleation of the Leydig cell tumor. At 9 and 44 months of followup they have maintained normal ipsilateral testicular volume compared to the contralateral gonad, and 1 patient entered puberty spontaneously at 1 year postoperatively. Neither patient suffered any morbidity, and both have presumably benefited from preservation of the involved gonad with preserved testicular volume. Prepubertal boys with isosexual precocious pseudopuberty, an isolated testis mass, increased testosterone and low or normal gonadotropin levels can reliably be diagnosed with Leydig cell tumors. Based on the ability to establish the diagnosis preoperatively and the universal benign behavior of unilateral, prepubertal Leydig cell tumor, we believe these patients are best treated with testis sparing enucleation of the tumor. In view of the high likelihood that this tumor in prepubertal boys is benign, a transscrotal surgical approach should be considered.