先天性脊柱畸形合并泌尿生殖系统畸形发病情况及相关因素分析

目的 了解先天性脊柱畸形患儿中泌尿生殖系统畸形的发生率并探讨其与多种因素之间的联系.方法 选取2003年3月至2008年11月入院治疗的425例先天性脊柱畸形患儿,术前均行腹部B超了解泌尿生殖系统畸形情况、行脊柱CT了解脊柱畸形及脊柱内神经畸形、行心电图除外心脏异常,出现阳性结果行MRI及超声心动网以确诊.结果 先天性脊柱畸形患儿中泌尿生殖系统的发生率为11.8%(50/425),其发病与胎次、母亲年龄、出生地差异、脊柱畸形的分类、侧弯部位、侧弯方向以及是否合并心血管畸形、椎管内神经系统畸形均无统计学关系.泌尿生殖系统畸形的患儿出生时父亲年龄较无泌尿生殖畸形的患儿父亲年龄大(P=0.018),合并泌尿生殖系统畸形的患儿较易合并肋骨畸形(P=0.011).结论 先天性脊柱畸形患儿合并泌尿生殖系统畸形的发生率较高,需引起临床高度重视,从而给予适当处理.     

Association between WAGR syndrome and diaphragmatic hernia

Anomalies in WT-1 (Wilms' tumor gene), mapped to 11p13, cause Denys-Drash, Frasier and WAGR syndromes. WAGR syndrome is characterized by Wilms' tumor (W), aniridia (A), genitourinary anomalies (G) and mental retardation (R). In the early human fetus, WT-1 is expressed in the pleural and abdominal mesothelium, and consequently this gene may play a role in diaphragm development. The first report of an association between WAGR syndrome and congenital diaphragmatic hernia has recently been published. We present another infant with aniridia, left cryptorchidism with testicular dysgenesis, right-sided posterolateral diaphragmatic hernia and moderate psychomotor retardation, in whom genetic study showed a deletion of 11p13 and PAX-6, confirming the diagnosis of WAGR syndrome.     

One hundred three consecutive patients with anorectal malformations and their associated anomalies

OBJECTIVE: A long-term retrospective analysis of 103 infants with anorectal malformations (ARMs) was conducted to describe any associated congenital anomalies and surgical classifications. DESIGN: Retrospective medical record review. SETTING: This case series was conducted on all infants with ARMs born at, or referred to, any of 3 major medical centers in Wichita, Kan, for close to a 22-year period. PATIENTS: The 103 infants in this study represent a consecutive sample of patients with ARMs. Patients were separated into 2 groups: isolated ARMs without associated anomalies (n = 30), and ARMs with associated anomalies (n = 73). The male-female ratio was 2:1. MAIN OUTCOME MEASURES: Patients with associated anomalies were further classified into groups of ARMs with minor anomalies; major anomalies; chromosomal abnormalities; and malformation syndromes, associations, or sequences. Only anomalies that occurred more than once were reported. Malformations were also classified according to major organ systems. RESULTS: The incidence of ARMs in our study was approximately 1 in 2500 live births. Additional anomalies were found in 71% of infants with ARMs. Associated anomalies by major organ system included genitourinary anomalies (49%), musculoskeletal anomalies (43%), craniofacial anomalies (34%), cardiovascular anomalies (27%), gastrointestinal anomalies (18%), respiratory anomalies (13%), and central nervous system anomalies (12%). The most common chromosomal abnormalities were trisomies (8%), and ARMs were associated with VATER complex (vertebral defects, anal atresia, tracheoesophageal fistula with esophageal atresia, and radial and renal anomalies) in 11 cases (11%) and VACTERL (vertebral, anal, cardiac, tracheal, esophageal, renal, and limb anomalies) in 4 cases (4%). CONCLUSIONS: Patients with ARMs have a high incidence of associated congenital anomalies. Evaluation of the most commonly affected organ systems in these infants is essential because it is these associated anomalies that account for most of the morbidity and mortality that is associated with this condition.     

A novel WT1 gene mutation associated with wilms' tumor and congenital male genitourinary malformation

WT1 is located on the short arm of human chromosome 11 and consists of 10 coding exons. Mutations of this gene have been reported to be the cause of Wilms' tumor, congenital male genitourinary malformations, and/or renal disorders. We describe here a novel WT1 gene mutation, i.e. a point mutation at intron 7 (+2) in both the tumor and the germline cells of a patient with Wilms' tumor and congenital male genitourinary malformation, but without renal disorder. The position of the mutation is at a splice donor site of intron 7, which causes the splicing out of exon 7 and generates a truncated protein. This type of mutation in the WT1 zinc finger domain has not been reported before. The mutation is of paternal origin and is heterozygous in the germline cells. In the tumor cells, however, the maternal allele is largely lost, from 11p12 to 11p15, which results in maternal loss of heterozygosity. These results, together with the data from previous reports, suggest that WT1 may function in gonadogenesis, nephrogenesis, and Wilms' tumor tumorigenesis.     

A phase II study of diaziquone in children with recurrent or progressive solid tumors. Report from the Childrens Cancer Study Group

Seventy-two children with recurrent, progressive, or metastatic lymphomas and other solid tumors, exclusive of primary central nervous system (CNS) tumors, were treated with aziridinylbenzoquinone (AZQ, diaziquone) at 9 mg/m2/day by 30-min intravenous infusion for 5 days every 3 weeks. Fifty-four patients were evaluable for response. Three partial responses occurred, two in patients with recurrent Hodgkin's disease and one in a patient with intraocular retinoblastoma. Sufficient numbers of patients with osteosarcoma, neuroblastoma, and Wilms' tumor were evaluable to demonstrate inactivity of this dosing regimen in these tumor types. Numbers of evaluable patients for other tumor types were insufficient to conclusively demonstrate inactivity. Myelosuppression, which was profound and prolonged, was observed. As administered in this study, AZQ has marginal activity and severe myelotoxicity in children with solid tumors.     

Prenatal cocaine exposure and fetal vascular disruption

The question of the potential teratogenicity of cocaine has been raised by the increasing frequency of its abuse in the United States. In previous studies, an increased incidence has been documented of spontaneous abortion, placental abruption, prematurity, intrauterine growth retardation, and neurologic deficits in the infants of women who abused cocaine. More recently, it has been suggested in studies that fetal vascular disruption accompanying maternal cocaine abuse may lead to cavitary central nervous system lesions and genitourinary anomalies. In this article, 10 children born of women who abused cocaine are described, 9 of whom have congenital limb reduction defects and/or intestinal atresia or infarction. The spectrum of anomalies associated with embryonic and fetal vascular disruption accompanying maternal cocaine abuse is thus enlarged. The specific risk for congenital anomalies accompanying maternal cocaine abuse during an individual pregnancy is unknown. However, data from these patients and the available literature suggest that counseling pregnant women concerning cocaine use should incorporate warnings about the possibility of associated embryonic or fetal vascular disruption.     

Hepatoma in a child with neurofibromatosis.

A 6-year-old girl had neurofibromatosis and hepatocellular carcinoma (hepatoma). Although neurofibromatosis is a common disorder, hepatic cancers are rare in childhood. Hepatic cancer, Wilms' tumor, and adrenocortical neoplasia are all seen with increased frequency in association with certain congenital anomalies, particularly with hemihypertrophy and various hamartomas. Neurofibromatosis, a hamartomatous disorder, is also seen with these congenital anomalies and it is reported with an unusually high incidence in patients with Wilms' tumor. We therefore suggest that these disorders may be related.     

Aniridia-Wilms' tumor association and 11p interstitial deletion

An 11p interstitial deletion is reported in a severely mentally retarded boy with aniridia, genitourinary anomalies, and distinct craniofacial dysmorphism. At the age of 4 years a large Wilms' tumor of the right kidney was diagnosed.     

Congenital malformations in the newborn--a prospective study

In a prospective study of 4098 births the incidence of congenital malformations was 1.464 per 100 births. Major malformations were seen in 1.1% births and minor malformations in 0.4% births. Patterns of congenital anomalies included multiple anomalies (37.68%), CNS malformations (13.33%), alimentary tract anomalies (6.66%), cardiovascular malformations (8.99%), genitourinary malformation (6.66%), limb anomalies (13.33%), and anomalies of skin and appendages (13.33%). Factors like maternal age, hormone testing and drug ingestion during pregnancy, radiation exposure and maternal infections were identified as possible risk factors for congenital malformations in the newborn.     

Pediatric Central Nervous System Tumor Diagnosis,Complications, and Emergencies

Central nervous system tumors are the most common solid malignancy in childhood and the leading cause of cancer-related mortality in children. With an average of 13 new patients being diagnosed daily with a central nervous system tumor, many of these patients will present to the emergency department for evaluation and management. Furthermore, many children experience complications and/or adverse effects directly from the tumor itself, from multimodality treatment (ie, surgery, radiation therapy, and/or chemotherapy), and/or as long-term survivors. Oncologic emergencies include increased intracranial pressure, spinal cord compression, seizures/status epilepticus, central diabetes insipidus, and adrenal insufficiency. Evaluation and management by emergency medicine practitioners are critically important for these patients in all phases of their diagnosis and treatment and can contribute significantly to an improved prognosis.     

Genetics and epidemiology of Wilms' tumor: the French Wilms' tumor study.

A complete family history was obtained for 501 patients with Wilms' tumor, treated in departments of pediatric oncology in whole France. The information was collected by self-questionnaire and/or by interview of parents. The proportion of bilateral cases is 4.6% and there are 12 patients (2.4%) with a positive family history of Wilms' tumor. The affected relatives are most often distant and no first degree relative was affected. Apart from the well-known associations with aniridia, hemihypertrophy, genitourinary anomalies, Beckwith-Wiedeemann, and Drash syndromes, there is also a significant excess of congenital heart defects (P = .008) which remains to be explained. Several findings support the bimutational hypothesis such as earlier diagnosis and increased parental age in bilateral cases. No particular anomalies and no increased frequency of childhood cancer were found in patients' relatives. The frequency of Wilms' tumor in relatives was estimated to be less than 0.4% in sibs, 0.06% in uncles and aunts, and 0.04% in first cousins. These figures are very different from those found in retinoblastoma and suggest that the mechanism may be more complex in Wilms' tumor. This conclusion is in agreement with molecular biology studies in tumors and linkage analysis in multiple case families which suggest that more than one locus is involved.     

Treatment results for patients with localized,completely resected (Group I) alveolar rhabdomyosarcoma on Intergroup Rhabdomyosarcoma Study Group (IRSG) protocols III and IV, 1984–1997: A report from the Children's Oncology Group

Purpose

To assess local control, event‐free survival (EFS), and overall survival (OS) rates in 71 patients with localized, completely resected (Group I) alveolar rhabdomyosarcoma (ALV RMS) and their relation to radiation therapy (RT) on IRSG Protocols III and IV, 1984–1997.

Methods

Chart review and standard statistical procedures.

Patients and Tumors

Patients were 1–18 years at diagnosis (median, 6 years). Primary tumor sites were extremity/trunk (N = 54), head/neck (N = 9), genitourinary tract (N = 7), and perineum (N = 1). Thirty patients received VA ± C with RT; 41 received VA ± C alone. RT was assigned, not randomized.

Results

Fifty‐four patients had Stage 1 (favorable site, any size) or Stage 2 (unfavorable site, ≤5 cm) tumors. Eight‐year EFS was 90%, with 100% local control for 17 patients given RT. Eight‐year EFS was 88%, with 92% local control for 37 patients without RT; P = 0.52 for EFS comparisons, 0.3 for local control comparisons. In 17 Stage 3 patients (unfavorable site, tumors >5 cm, N0), 8‐year EFS was 84% with 100% local control in 13 patients given RT; 8‐year EFS was only 25% and local control 50% in 4 patients without RT. Local recurrence was the most common site of first failure in non‐irradiated patients.

Conclusion

Patients with Stage 1–2 ALV RMS had slightly but statistically insignificantly improved local control, EFS, and OS rates when local RT was given. The need for local RT in Stage 1–2 patients deserves evaluation in a randomized study. Local control, EFS, and OS rates were significantly improved in Stage 3 patients receiving local RT. Pediatr Blood Cancer. 2010;55:612–616. © 2010 Wiley‐Liss, Inc.     

Association between maternal prenatal vitamin use and congenital abnormalities of the genitourinary tract in a developing country

ObjectiveTo determine the association between prenatal multivitamin supplementation and congenital genitourinary tract anomalies in a group of Colombian newborn babies included in the Latin-American surveillance program (ECLAMC).Study designWe included all neonates born between January 2004 and August 2007 registered in the ECLAMC database. Maternal prenatal multivitamin use was assessed for 122 newborns with congenital genitourinary tract anomalies and then compared to 271 non-malformed controls.Results46,850 births were registered and 122 (26/10,000) of them were identified to have a genitourinary tract anomaly. Prenatal multivitamin supplementation during the first, second, and third trimesters of pregnancy was associated with a reduction in the risk of these anomalies: OR 0.16 (0.08–0.31), OR 0.31 (0.19–0.52), and OR 0.38 (0.23–0.63) respectively.ConclusionsMaternal prenatal multivitamins may reduce the risk of congenital genitourinary tract anomalies, not only during the first 8 weeks of gestation but also later in pregnancy, in developing countries.     

Treatment of children and adolescents with localized parameningeal sarcoma: experience of the Intergroup Rhabdomyosarcoma Study Group protocols IRS-II through -IV, 1978-1997

BACKGROUND: We reviewed 611 patients with parameningeal sarcoma entered on Intergroup Rhabdomyosarcoma Study Group (IRSG) Protocols-II through IV (1978-1997), to delineate treatment results and evaluate prognostic factors. PROCEDURE: Primary sites were the middle ear/mastoid (N = 138), nasopharynx/nasal cavity (N = 235), paranasal sinuses (N = 132), parapharyngeal region (N = 29), and the pterygopalatine/infratemporal fossa (N = 77). Treatment was initial biopsy or surgery followed by multiagent chemotherapy and radiation therapy (XRT). Beginning in 1977, patients with cranial nerve palsy, cranial base bony erosion, and/or intracranial extension at diagnosis were considered as having meningeal involvement. They received triple intrathecal medications, whole brain XRT, and then spinal XRT. These treatments were successively eliminated from 1980 to 1991. RESULTS: The 611 patients' overall survival rate at 5 years was 73% (95% confidence interval, 70-77%). Favorable prognostic factors were: age 1-9 years at diagnosis; primary tumor in the nasopharynx/nasal cavity, middle ear/mastoid, or parapharyngeal areas; no meningeal involvement; and non-invasive tumors (T1). Thirty-five of 526 patients (6.7%) with information about presence/absence of meningeal involvement at diagnosis developed central nervous system (CNS) extension at 5-164 weeks (median, 46 weeks) after starting therapy. The estimated 5-year cumulative incidence rate of CNS extension during the study period was 5-7% (P = 0.88). CONCLUSIONS: Biopsy, XRT to the target volume, and systemic chemotherapy are successful treatments for the large majority of patients with localized parameningeal sarcoma. Carefully defining and irradiating the initial volume should reduce the risk of CNS failure. Aggressive initial surgical management of these patients is unnecessary.     

Spectrum of congenital malformations in the newborn

Of 6,274 consecutive live-births during 1975–78, 170 (2.7 percent) infants were diagnosed to have 241 major congenital malformations. The incidence of malformations among preterm was almost twice (5.3 per cent), while two-thirds of infants with internal malformations weighed less than 50th centile for their gestational age at birth. Musculoskeletal defects accounted for one-third of all malformations. Out of systemic defects, central nervous system anomalies were most frequent (12.9 per cent) while other system defects (except respiratory system) had an identical frequency of about 10 per cent. The incidence of neural tube defects was found to be 7 per 1000 total births. Among individual anomalies, club foot, spina bifida, polydactyly, left-to-right cardiac shunt, clef lip ±cleft plate, hydrocele, Down syndrome and congenital dislocation of hips had a frequency greater than 1 per 1000 live-births.     

Surgical management of extremity rhabdomyosarcoma: A consensus opinion from the Children's Oncology Group,the European Pediatric Soft-Tissue Sarcoma Study Group,and the Cooperative Weichteilsarkom Studiengruppe

The treatment of extremity rhabdomyosarcoma remains a challenge due to several adverse prognostic factors frequently associated with this tumor site. The International Soft-Tissue Sarcoma Database Consortium (INSTRuCT) is a collaboration of the Children's Oncology Group Soft-Tissue Sarcoma Committee, the European Pediatric Soft-Tissue Sarcoma Study Group, and the Cooperative Weichteilsarkom Studiengruppe. The INSTRuCT surgical committee developed an internationally applicable consensus opinion document for the surgical treatment of extremity rhabdomyosarcoma. This document addresses surgical management, including biopsy, nodal staging, timing of therapy, resection and reexcision, reconstruction, and surgical approach at relapse.     

Clinical and biological aspects of acute lymphoblastic leukemia in 62 infants: Retrospective analysis of the Tokyo Children's Cancer Study Group

BACKGROUND: As a first step to formulate a new treatment strategy for refractory acute lymphoblastic leukemia (ALL) in infants, clinical results and immunophenotypic and cytogenetic data were analyzed and compared with those from overseas. METHODS: There were 62 infants with ALL who were treated between 1977 and 1995 at 30 institutions affiliated with the Tokyo Children's Cancer Study Group. Clinical and laboratory data obtained from these infants (all under 1 year of age) were retrospectively studied. RESULTS: The morphological diagnoses were FAB-L1 for 51 patients (82.2%) and FAB-L2 for 11 patients (17.8%). Hepatomegaly and splenomegaly were found in 40 (70.0%) and 40 patients (68.3%), respectively. The mean (+/- SEM) leukocyte count at diagnosis was 205,900 +/- 35,700/microL. The involvement of the central nervous system was evident in nine of 36 patients who were subjected to lumbar puncture, while three of these nine patients were free of neurological symptoms at diagnosis. Thirty-one patients (55.4%) were CD10 negative and 14 (25.0%) were CD10 positive. Thirty-one of 47 patients (65.9%) exhibited chromosomal abnormalities, including 28 patients (59.6%) with 11q23 abnormalities. Rearrangements in the MLL gene were found in nine of 13 infants (69.2%) examined. Translocation of 11q23 and/or MLL gene rearrangement (11q23/MLL) was significantly associated with the absence of the CD10 antigen. Hyperleukocytosis of more than 50,000/microL and 11q23/MLL gene rearrangements were related to a poor prognosis. The probability of an event-free survival in 62 infants was 13.1 +/- 4.8% at 48 months. CONCLUSIONS: New therapeutic strategies and large-scale cooperative prospective trials are needed to improve the prognosis of ALL in infants.     

WAGR syndrome: a clinical review of 54 cases

WAGR syndrome is a rare genetic disorder characterized by a de novo deletion of 11p13 and is clinically associated with Wilms' tumor, aniridia, genitourinary anomalies, and mental retardation (W-A-G-R). Although the genotypic defects in WAGR syndrome have been well established, the large variety of phenotypic manifestations of the syndrome has never been reported. We report on 54 cases of WAGR syndrome to demonstrate both the classical clinical signs and nonclassical manifestations found in a large population of individuals with this disorder. An understanding of WAGR syndrome and its clinical findings can provide important insight regarding the functions of the involved genetic region. Recommendations for diagnosis, evaluation, and surveillance of patients with WAGR syndrome are also presented.     

Focal segmental glomerulosclerosis in patients with complete deletion of one WT1 allele

The renal prognosis of patients with Wilms' tumor, aniridia, genitourinary anomalies, and mental retardation syndrome (WAGR) is poor. However, the renal histology and its mechanisms are not well understood. We performed renal biopsies in 3 patients with WAGR syndrome who had heavy proteinuria. The complete deletion of one WT1 allele was detected in each patient by constitutional chromosomal deletion at 11p13 using G-banding, high-resolution G-banding, and fluorescence in situ hybridization. The patients exhibited proteinuria at the ages of 6, 10, and 6 years and were diagnosed as having focal segmental glomerulosclerosis (FSGS) at the ages of 7, 16 and 19 years, respectively. They exhibited normal or mildly declined renal function at the time of biopsy. Re-examination of a nephrectomized kidney from 1 patient revealed that some glomeruli showed segmental sclerosis, although he did not have proteinuria at the time of nephrectomy. The other 2 patients did not develop Wilms' tumor and thus did not undergo nephrectomy, chemotherapy, or radiotherapy, thereby eliminating any effect of these therapies on the renal histology. In conclusion, complete deletion of one WT1 allele may induce the development of FSGS. Our findings suggest that haploinsufficiency of the WT1 could be responsible for the development of FSGS.     

Congenital malformations in Shimla

Congenital malformations were studied over a period of five years in 10, 100 consecutive births including still births at Indira Gandhi Medical College, Shimla. Out of these, 180 babies had one or the other congenital malformations and the overall incidence was 1.78%. Amongst the 311 still born babies 47 had congenital malformations indicating that the incidence of congenital malformations was much higher in still born babies (15.1%) as compared to the live born babies (1.3%). The malformations involving the central nervous system were the commonest (40%) followed by musculoskeletal system (23.8%) while genitourinary system malformations were the least common and accounted for 3.8% of the cases. Incidence of congenital malformations was the highest in mothers over 35 years of age and gravida four and more. The incidence was 2.8% in both the groups; the incidence of congenital malformation was more in babies weighing < 2500 gms and was 2.6%.