Neuroblastoma mass screening in children.
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Humans↗
Biomedical subjects
R Kerbl
Publications and source records attributed to R Kerbl.
Neuroblastoma screening in infants postponed after the sixth month of age: a trial to reduce "overdiagnosis" and to detect cases with "unfavorable" biologic features.
BACKGROUND: Encouraged by Japanese reports of the benefits of screening 6 month-old infants for neuroblastoma, a neuroblastoma screening program was introduced in Austria in 1991. However, because of concerns related to "overdiagnosis" by screening at this age, the screening test was performed at a later age. METHODS: From March 1991 to February 1995 neuroblastoma screening was performed on filter paper urine specimens in 100,043 Austrian infants (median age 8.5 months). Primary analysis of urine catecholamines (vanillylmandelic acid and homovanillic acid was performed by use of an E1A method. Questionable or positive results were confirmed by high performance liquid chromatography (HPLC). A double retest was requested following a positive HPLC result. RESULTS: Twenty-one infants were admitted to a hospital following repeatedly elevated values of vanillymandelic acid (VMA) and/or homovanillic acid (HVA). Eleven infants were found to have neuroblastoma (three stage 1, four stage 2B, four stage 3). Treatment consisted of surgery alone with total or subtotal resection in eight cases, surgery and chemotherapy in two cases, and chemotherapy alone in one case. Biologic features were assessed in all tumors excluding ploidy in one case. The majority of the tumors analyzed were near-triploid (9/10), however, two tumors revealed N-myc amplification. CONCLUSIONS: Our results demonstrate that stage distribution and biologic features of neuroblastomas diagnosed by screening at 8.5 months are different from the results of screening at 6 months. Furthermore, the detection of one neuroblastoma among 9,100 screened infants is significantly lower than the incidence of the Japanese screening program. Our results suggest that screening at an age of 7 to 10 months reduces overdiagnosis and may be of more benefit than earlier screening.
Age Factors↗
Feasibility of peripheral blood stem cell (PBSC) and peripheral blood mononuclear cell (PBMNC) separation in children with a body weight below 20 KG.
Nine children from 10 to 76 months (median 28.0), weighing 8.5 to 19.7 kg (median 13.0 kg) underwent peripheral blood stem cell separation (PBSCS) or peripheral blood mononuclear cell separation (PBMNCS), after insertion of a double-lumen central venous catheter (8-10 French). Separations were performed with a continuous flow blood separator (Fen-wall CS 3000 plus), running a specially adopted separation-program. In 7 children (5 with neuroblastoma IV, 1 with multifocal Ewing's sarcoma, and 1 with rhabdomyosarcoma IV), stem cells were mobilized by application of G-CSF at a dosage of 15-27.7 micrograms/kg body weight (median 16.25) subcutaneously following high-dose chemotherapy, according to the disease-related protocols, whereas 2 children had PBMNCS to induce graft vs. leukemia (GvL)-reaction in the HLA-identical sibling suffering from relapsed chronic myelogenous leukemia (CML: n = 1), or chronic myelomonocytic leukemia (CMML: n = 1) after allogeneic BMT. In all cases, the collecting procedure was performed after filling the cell separator with priming solution consisting of 2 U of irradiated and washed packed red cells, 250 ml human albumin, and 0.9% NaCl. In the 7 patients with solid tumors between 0.45 and 62.7 x 10(6) CD-34 positive cells/kg body weight were separated; the patient who had the lowest yield was separated twice after another mobilizing course. Three patients (2 with neuroblastoma IV and 1 with multifocal Ewing's-sarcoma) underwent a double transplantation with 1-3 portions of the collected stem cells within a 5- to 6-week interval. Two children had a rapid engraftment on both peripheral blood stem cell transplantations (PBSCTs). The third child, who had the lowest yield and was separated twice had prompt engraftment at the first PBSCT but delayed and incomplete engraftment at the second PBSCT. One patient after adoptive immunotransfer with PBMNCs for relapsed CML is now 40 months in complete cytogenetic and molecular biological remission, whereas the other patient treated for relapsed CMML did not respond to the PBMNC-transfusion. The results indicate that PBSCS and PBMNCS can be performed in children with a body weight below 20 kg.
Antigens, CD34↗
Determination of homovanillic acid and vanillylmandelic acid in neuroblastoma screening by stable isotope dilution GC-MS.
A method for the quantitative determination of homovanillic acid (HVA) and vanillylmandelic acid (VMA), two metabolites of catecholamines, is presented. The assay is based on gas chromatography/electron impact mass spectrometry. The preparation of 13C-labeled VMA from [13C6]vanillin is described. Together with purchased deuterated HVA the 13C-labeled VMA is used as an internal standard in stable isotope dilution GC/MS. The method involves elution from soaked filter-papers, determination of creatinine content, extraction of HVA and VMA from eluted and urinary samples and derivatization to the di-and tri(trimethylsilyl) derivatives, respectively. The detection limits were found to be 4.0 pg for HVA and 0.8 pg for VMA. The method was applied to the routine determination of urinary HVA and VMA in a range from 5 to 100 ng HVA and VMA per microgram creatinine. The lower limits of pathological concentrations are set at 35 ng micrograms-1 creatinine for HVA and to 20 ng micrograms-1 creatinine for VMA, which are in close correlation with the values from other methods, but with the main advantage of reducing the amount of questionable or elevated results from 6.7% (high-performance liquid chromatography (HPLC) alone) to 0.9% (HPLC and GC/MS).
Calibration↗
Connatal localized neuroblastoma. The case to delay treatment.
BACKGROUND: Spontaneous regression is well documented for a subset of widespread neuroblastomas (Stage 4S) and for localized residual tumors after incomplete resection. Possible spontaneous regression of untreated localized neuroblastoma in infants is frequently discussed, but has very rarely been demonstrated clinically. METHODS: We report four patients with localized neuroblastomas detected early; all were tumors of the adrenal gland. One patient was detected antenatally by ultrasound, the other three tumors were detected incidentally by sonography at age of birth, 1 week, and 7 weeks, respectively. In three patients treatment was delayed in order to await a possible spontaneous regression, and in one patient treatment was delayed due to an uncertain diagnosis. RESULTS: Local tumor growth was observed in three patients, and the tumors were removed 7, 12, and 16 weeks, respectively, after the initial diagnosis of the neuroblastoma. All three patients are free of disease. The fourth patient developed liver metastases 4 weeks after the first suspicion of neuroblastoma. Progressive disease ended in death at the age of 17 months. CONCLUSIONS: None of the four patients showed spontaneous tumor regression. Noninvasive examinations and invasive investigations (in two patients) were unable to predict the tumor's behavior. Based on present knowledge, a general "wait and see" strategy cannot be recommended for early and incidentally detected neuroblastoma patients.
Adrenal Gland Neoplasms↗
Congenital central hypoventilation syndrome (Ondine's curse syndrome) in two siblings: delayed diagnosis and successful noninvasive treatment.
UNLABELLED: Congenital central hypoventilation syndrome (CCHS, Ondine's curse syndrome) is a rare respiratory disorder; less than 100 cases have been reported. Familiality of the disease has been discussed, but only few familial cases have been reported so far. In this report we describe the occurrence of CCHS in two male siblings. Diagnosis was established only at the age of 4 years in the first case, although the patient had disease related symptoms since early infancy. The second patient was one of dizygotic twins, he was diagnosed with CCHS at the age of 8 months. Up to that age only moderate desaturations had been observed. The other twin was unaffected by the disease. Both patients were successfully treated by nocturnal positive-pressure ventilation via a specially adapted face mask. They show satisfactory physical and neurologic development. CONCLUSION: Our cases support the assumption of familiality in CCHS although the mode of inheritance remains to be clarified. Polygraphic recordings including capnography should be performed in siblings of CCHS patients early in life in order to avoid secondary complications. Noninvasive treatment by ventilation via special face masks is feasible.
Child↗
Screening for neuroblastoma in late infancy by use of EIA (enzyme-linked immunoassay) method: 115000 screened infants in Austria.
The aim of this study was to investigate the feasibility of a neuroblastoma screening programme for children in late infancy, based on collaboration of general paediatricians and practitioners in Austria, using the technique of enzyme-linked immunoassay (EIA) for biochemical analyses. Analysis of catecholamine metabolites in spot urine samples by EIA with high performance liquid chromatography as a backup was undertaken. Austrian infants (median age 8.7 months) were screened. Overall compliance was 30%. The EIA method had a high rate (6.7%) of false-positive results. 28 infants were admitted to hospital. In 15 cases, neuroblastoma was found (four stage 1, five stage 2B, six stage 3). The EIA method can be used for neuroblastoma screening, but requires a backup analytical technique in order to avoid unnecessary hospital admissions. The stage distribution and biological features of neuroblastomas diagnosed by screening at a later age are different from those detected by earlier screening. Screening in late infancy might be of more benefit than early screening.
Austria↗
Comparison of the diagnostic and prognostic value of biological markers in neuroblastoma. Proposal for a common methodology of analysis. SENSE group.
BACKGROUND: The prognosis of pediatric neuroblastoma depends both on clinical presentation and on certain cellular and molecular characteristics. Screening programs have been initiated in infants of less than one year of age, based on the hypothesis that neuroblastoma progresses from early to late clinical stages through a classical multistep process linked to an accumulation of molecular abnormalities. However, recent analyses suggest that most cases discovered by screening are low stage tumors considered as dysembryogenetic residues devoid from major abnormalities and that high-grade tumors with molecular abnormalities are unrelated diseases. AIM OF THE REVIEW: To confirm one or the other hypothesis, and eventually identify biological factors possibly responsible for the initiation and progression of the disease, it is of utmost importance that all investigators agree on biological criteria for analysis when neuroblastoma tissue is available in screened and unscreened populations. This paper reviews the biological tools available for prognosis in neuroblastoma, the priority for analysis of biological markers according to both methodological reliability and feasibility, and the conditions of tissue storage for further analysis of these biological markers. CONCLUSION: The standardized biological evaluation of neuroblastoma will allow to collect sufficient data for multivariate analysis; such analysis is now fundamental if one wants to clearly define the respective impacts of biological abnormalities on neuroblastoma progression.
Biomarkers, Tumor↗
[5 years neuroblastoma screening in Austria: rate of participation, results and a comparison with other screening areas].
In late 1990 a screening program for the early detection of neuroblastoma in infants was introduced in Austria. The program is performed on a voluntary basis in collaboration with general pediatricians and practitioners. Filter strips for urine collection are distributed to parents of infants aged seven to nine months on the occasion of a routine check up. The samples are sent to the laboratory by parents and analysed for vanillylmandelic acid (VMA) and homovanillic acid (HVA). Between January 1991 and December 1995 125,201 infants were screened. The compliance rate was 26.8% for Austria, but great differences were seen for different regions (65% in Carinthia, 10% in Vorarlberg). 30 children were admitted to hospital for investigation of repeatedly elevated urine catecholamines. A neuroblastoma was identified in 16 cases. In 12 of these cases at least one unfavorable prognostic factor was present (stage > or = 3, elevated LDH, unfavorable histology, N-myc amplification, di- or tetraploidy). Neuroblastoma screening of infants aged more than six months seems to detect predominantly those tumors which are unlikely to regress spontaneously. The observation of one false negative case, however, demonstrates that neuroblastomas which become clinically manifest at a later date may remain undetected by early screening. Possible advantages of shifting screening to a later age and repeated screening are discussed.
Austria↗
[Sudden infant death (SIDS) in Austria. How reliable is the diagnosis?].
The sudden infant death syndrome (SIDS) is the most frequent cause of death during the postneonatal period (2-12 months) in Austria. A retrospective analysis of the SIDS cases registered between 1988 und 1992, however, shows marked differences between the provinces with regard to the relative proportion of SIDS against total infant mortality figures. The use of different definitions for SIDS seems to be responsible for local differences. Thus, a standardized investigation for all sudden unexpected deaths is required (autopsy, histological investigations, death scene investigation). Furthermore, a uniform classification for sudden unexpected infant death should be applied.
Austria↗
Neuroblastoma with N-myc amplification detected by urine: mass screening in infants after the sixth month of life.
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Diploidy↗
[Sudden infant death. Risks and possibilities of prevention].
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Humans↗
Anesthetic management of marrow harvesting from a 7-week-old premature baby.
Bone marrow was harvested from a 3.95 kg premature 7-week-old female baby for donation to a 13 kg HLA-identical sister with severe aplastic anemia. Two hundred ml of donor bone marrow were aspirated, containing a calculated dose of 3 x 10(8)/kg nucleated bone marrow cells for the recipient. This was equivalent to two-thirds of the donor's calculated blood volume (320 ml). Peri-operative care included invasive monitoring of intravascular pressures, arterial blood gas analysis, careful temperature control and the infusion of 150 ml of packed red cells, 150 ml of colloid and 50 ml of crystalloid. Rapid engraftment occurred. There were no complications and both donor and recipient are healthy 12 months later.
Anemia, Aplastic↗
Effects of naloxone on apnoea duration during sleep in infants at risk for SIDS.
The effects of intravenous injections of the opiate antagonist naloxone (0.005-0.4 mg/kg body weight) on respiratory pattern, apnoea duration and frequency were investigated in six infants with severe sleep apnoea syndrome. Since several authors found elevated plasma- and CSF-levels of endogenous opioids (endorphines) in infants with sleep apnoea syndrome, we wanted to determine whether the impairment of the control mechanisms of respiration during sleep is due to an effect of endogenous opioids. Independent of the dose, naloxone did not exert any effect on respiratory pattern and occurrence of periodic apnoea. We were unable to prove that endorphines play a major role in pathogenesis of sleep apnoea syndrome in infancy and possibly in sudden infant death syndrome (SIDS). We speculate that elevated levels of endorphines reported by some investigators rather seem to be a consequence of hypoxic stress than a cause for sleep apnoeas.
Aminophylline↗
[Sleep apnea in infants and the risk of SIDS].
The examination of the respiratory function in 184 sleeping infants gave evidence of a significant difference in several parameters between the so-called SIDS risk group and the control group. The risk group (97 babies) consists of 60 infants with frequent prolonged apneas, 30 infants with postnarcotic apneas and 7 near miss infants. Polygraphic registration during sleep showed significantly more apneas in the risk group. These apneas often appeared more frequently during certain periods. The average respiratory deficit expressed as the MA-value (MA = average apnea duration) in the risk group was significantly higher than in control infants. Besides that we were able to prove a more frequent pathological gastroesophageal reflux in the risk infants than in control infants.
Anesthesia, General↗
Coordination of sucking, swallowing and respiration in infants with sleep apnea syndrome.
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Deglutition↗
Visceral manifestation of cat scratch disease in children. A consequence of altered immunological state?
A 12-year-old girl with a 2-month history of fever and abdominal pain was admitted to our hospital. Ultrasound and CT scans of the abdomen showed multiple hypoechoic lesions of liver and spleen. Screening for zoonosis revealed high positive titers to Bartonella henselae. T-cell deficiency was demonstrated and remained almost unchanged during a follow-up of 11 months. A review of the literature shows that disseminated visceral affection is a rare presentation of cat scratch disease (CSD) in childhood and adolescence. Further immunological investigations are needed in more patients with CSD to confirm whether an altered immunological state may be responsible for the atypical visceral manifestation of CSD.
Animals↗
[Peripheral lymphadenopathy in childhood--recommendations for diagnostic evaluation].
BACKGROUND: Enlargement of peripheral lymph nodes most commonly caused by a local inflammatory process is frequently seen in childhood. The aim of the present study was to analyze the most common causes of peripheral lymphadenopathy and to develop a simple algorithm for the primary diagnostic evaluation of peripheral lymph node enlargement in this age group. PATIENTS: Between April and September 1999 87 unselected children (median age: 5 1/2 years) with peripheral lymphadenopathy were referred to the Department of Pediatrics, University of Graz, for further investigation. RESULTS: EBV infection was diagnosed in 20 (23.0%) children. 19 (21.8%) patients had acute bacterial lymphadenitis. In 21 (24.1%) patients lymph node enlargement was classified as "post/parainfectious (viral)". Four patients each had toxoplasmosis and cat scratch disease. In 11 (12.6%) patients neither physical nor laboratory examinations revealed pathologic results. Among the remaining 8 children sarcoidosis and Hodgkin disease was diagnosed in one patient each. Small, soft, mobile, nontender, cervical, axillary or inguinal lymph nodes do not require further investigations. In case of enlarged, tender lymph nodes with overlying skin erythema and fever diagnostic evaluation should include complete blood count, erythrocyte sedimentation rate and/or c-reactive protein level, supplemented by appropriate antibody testing (EBV, CMV, Toxoplasma gondii, Bartonella henselae). Firm, enlarged, painless lymph nodes which are matted together and fixed to the skin or underlying tissues necessitate a more detailed diagnostic evaluation in order to exclude malignant or granulomatous diseases. CONCLUSIONS: Our study demonstrated that primary diagnostic evaluation of childhood peripheral lymphadenopathy is mainly based on clinical grounds. In most cases a small number of additionally performed laboratory tests allow to correctly identify the cause of the peripheral lymph node enlargement.
Adolescent↗