[Congenital fetal neuroblastoma]. / Neuroblastome congénital foetal.

Neuroblastoma are pediatric tumors of neural crest origin, most often localized in adrenal glands and infrequently congenital. We report two fetal cases found at autopsy, performed at 24 and 28 weeks of gestation, respectively. The 24 week old fetus did not show any malformation; systematic histological analysis found neuroblastoma cells in both the adrenal glands and the retroperitoneal fat tissue. The 28 week old fetus was hydropic and exhibited a nodule (3 cm) in the posterior mediastinum, next to the thoracic spinal cord. This tumor responded to a neuroblastoma associated with small metastatic foci in the adrenal glands, the liver and the frontal brain cortex. The placenta was abnormally heavy and showed hemorrhagic and necrotic areas. Microscopically plugged clumps of neuroblastoma cells were found inside fetal vessels. Immunohistochemistry was employed in both cases and the cells showed immunoreactivity for NSE, NB 84, chromogranin, synaptophysin and neurofilaments, while desmin, MIC 2, and protein S-100 were negative. Congenital neuroblastomas are rare and, to our knowledge this is the thirteenth report of congenital neuroblastoma associated with placental metastasis.

Bloodstream infections in children with cancer: a multicentre surveillance study of the Italian Association of Paediatric Haematology and Oncology. Supportive Therapy Group-Infectious Diseases Section.

A one-year prospective, multicentre surveillance study on aetiology, main clinical features and outcome of bloodstream infections in children with cancer was conducted in 18 paediatric haematology centres belonging to the Italian Association for Paediatric Haematology and Oncology. A total of 191 bloodstream infections were reported during the study period. Of them, 123 (64%) occurred in neutropenic and 68 (36%) in non-neutropenic patients. Gram-positive cocci caused 45% (85/191) of the episodes, gram-negative rods 41% (78/191), and fungi 9% (18/191). The remaining 5% (10/191) of the episodes were poly-microbial infections. A total of 204 pathogens were isolated (46% gram-positive cocci; 44% gram-negative rods; and 10% fungi). The aetiologic distribution was similar among neutropenic and non-neutropenic patients. A correlation between the infection and the presence of an indwelling central venous catheter was found in 20% (23/114) of the episodes among neutropenic patients and in 55% (23/62) among non-neutropenic patients. Gram-negative micro-organisms were isolated in an unusually high proportion of catheter-related infections (48%). The overall mortality rate from any cause within 30 days from the first positive blood culture was 11%, and was higher among patients who were neutropenic at the onset of the infection than among those who were not neutropenic (15 versus 4%, P = 0.03). In addition, the mortality was significantly higher in recipients of bone marrow transplantation than in patients with acute leukaemia or solid tumour (21, 11 and 6%, respectively) and was also higher in fungaemias and poly-microbial infections (22 and 30%) than in single gram-positive and gram-negative bacteraemias (11 and 6%).

Mutational screening of thrombopoietin receptor gene (c-mpl) in patients with congenital thrombocytopenia and absent radii (TAR).

Thrombocytopenia with absent radii (TAR) is a rare autosomal recessive disease characterized by hypomegakaryocytic thrombocytopenia and bilateral radial aplasia. We performed mutational screening of coding and promoter regions of the c-mpl gene, encoding thrombopoietin (TPO) receptor, by sequence analysis in four unrelated patients affected by TAR syndrome. Our results indicate that c-mpl gene mutations are not a common cause of thrombocytopenia in TAR syndrome.

Short stature and body proportion in thalassaemia.

Short stature and short trunk have been reported in thalassaemic patients. We report a study on stature and body proportions in 476 patients (2-36 years old) with beta-thalassaemia major, followed in 12 Italian centres. Auxological data (standing height, sitting height, subischial leg length, target height), haematological data (age at first transfusion, age at start of desferrioxamine [DFX] chelation, mean dose of DFX, ferritin values) and information regarding the presence of endocrine disorders and of bone lesions, were collected and analysed according to the age of the patients, in order to investigate the natural history of the disproportion and the role of siderosis, DFX toxicity and endocrine disorders. Our data indicate that about 18% of thalassaemic patients exhibit short stature; disproportion between the upper and lower body segments is present in 14%; however, a short trunk despite normal stature is present in another 40% of patients. This is due to a spinal growth impairment which starts in infancy and progressively aggravates. We think that a short trunk is peculiar to the disease itself; however, other factors such as hypogonadism, siderosis, or DFX-induced bone dysplasia are probably involved in aggravating the body disproportion in these patients.

Long-term GnRH-agonist administration revealed a GnRH-independent mechanism stimulating FSH discharge in humans.

The present study evaluated the FSH and LH episodic discharge in different physiopathological conditions undergoing chronic GnRH-agonist administration. Four girls with true precocious puberty and five postmenopausal women were administered GnRH-agonist (3.73 leuprolide acetate every 4 weeks; Takeda Italia, Rome, Italy) for at least 4 months. Plasma LH and FSH secretory profiles were assessed before and under GnRH-agonist administration (after 21 and 120 days). Pulsatility studies were conducted for 4 h in the girls and for 6 h in postmenopausal women, with blood sampling intervals of 10 min. Pubertal and postmenopausal patients showed the distinct episodic co-secretion of LH and FSH before GnRH-agonist administration; this co-secretion disappeared in both groups after 21 and 120 days of treatment. Moreover, while LH concentrations decreased to almost undetectable levels and LH episodic release disappeared, FSH plasma levels were only partially reduced and FSH episodic secretion was detectable in both groups. In conclusion, this study demonstrated that long-term GnRH-agonist administration blocked LH but not FSH episodic release. These data enforce the hypothesis that FSH episodic discharge might be dependent not only on hypothalamic GnRH, but also on a GnRH-independent stimulatory pathway.

Primary hypergammaglobulinemic purpura associated with IgG2 deficiency. A case report.

Hypergammaglobulinemic purpura is a rare disease in children. We report a case of a 12 year-old girl with a history of frequent infections. We found the presence of IgG2 deficiency despite polyclonal hypergammaglobulinemia. An IgG subclass determination should be obtained in every child with polyclonal hypergammaglobulinemia and features of immunodeficiency.

Intrinsic secretory characteristics of luteinizing hormone and prolactin episodic release during pubertal development.

The intrinsic characteristics of LH and prolactin (PRL) episodic secretion were evaluated in a group of 18 children (8M and 10F). The children were divided into two groups according to the Tanner stage: Group A (Tanner < or = 1, N = 7, 3M and 4F, 6-10 years of age) and group B (Tanner 2-3, N = 11, 5M and 6F, 9-11 years of age). A pulsatility study of 4 h, sampling every 10 min, was carried out in all children. LH and PRL plasma levels were assayed by IFMA and RIA respectively. LH and PRL secretory episodes were then identified on plasma determinations using the program DETECT. Instantaneous secretory rates (ISR) were then computed for both LH and PRL using the specific algorithm within the DETECT program. Plasma LH levels were different between the two groups of children. Group A children showed undetectable LH plasma levels (below the minimal detectable dose of 0.1 mIU/ml), while group B demonstrated LH plasma levels in the normal range of values for age and sexual development (1.5 +/- 0.3 mIU/ml, mean +/- SEM). LH pulse frequency for group B was 3.2 +/- 0.4 peaks/4 h. No significant differences in mean plasma PRL levels, pulse frequency and pulse amplitude were observed between the two groups of children. Computation of ISR for LH (group B only) and PRL (both groups) identified the intrinsic episodic characteristics of the two hormones. No significant differences in LH and PRL pulse frequencies were observed when comparing the results estimated on ISR with those estimated on plasma concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

[Use of high-dose intravenous immunoglobulins in pediatric hematology]. / L'uso di immunoglobuline endovena ad alte dosi in ematologia pediatrica.

High-dose intravenous immunoglobulin play a critical role in a lot of pediatric hematologic diseases. In our experience we studied the effects of IVIG treatment in 63 children. They all tolerated IVIG preparations in every infusions; no trouble caused the interruption of treatment. The efficacy is evident in immunomediated diseases, most of all ITP, and controlling septic episodes in immunocompromised patients (ALL, AIDS, marrow bone transplantation). An important problem is the cost of preparation; but we may consider that this treatment, for example in ITP, reduces hospitalization for children, necessity of platelets' transfusions, use of steroids and, therefore, their collateral effects. Hence, we assert that the social cost of the management of ITP disease is not higher in children treated with IVIG. Furthermore, short hospitalization for IVIG therapy contributes to accept this disease. It should be advisable to make controlled studies to define with more accuracy the role of this preparation and the modality of its use in the different clinical conditions in which it is employed.

Acute beta-interferon or thymopentin administration increases plasma growth hormone and cortisol levels in children.

The interaction between the immune and endocrine systems has recently been investigated. Hodgkin's disease represents a model of immune disturbance frequently associated with endocrine impairment. The present study evaluated the effect of the acute administration of beta-interferon or thymopentin on plasma growth hormone, prolactin and cortisol levels in children with Hodgkin's disease (N = 8) and age- and sex-matched healthy controls (N = 8). beta-interferon (1,000,000 IU), thymopentin (50 mg) or placebo (saline) were injected after two basal blood samples (-15 and 0) and further samples were drawn at 15, 30, 45, 60, 90 and 120 min. Plasma growth hormone, prolactin and cortisol levels were measured by specific RIAs. Plasma prolactin levels did not show significant change following beta-interferon or thymopentin injection in either the controls or the patients. In the patients with Hodgkin's disease, beta-interferon injection induced a significant increase in both plasma growth hormone and cortisol levels, while thymopentin was not effective. In controls both thymopentin and beta-interferon administration increased plasma growth hormone and cortisol levels. These results indicate that beta-interferon and thymopentin are immune substances active on the release of growth hormone and cortisol in healthy children. The lack of effect of thymopentin in children with Hodgkin's disease suggests an impairment of the immune-endocrine interaction in these patients.

Reduced spinal bone density in young women with amenorrhoea.

To assess the influence of diminished oestrogen production on bone density, we studied 23 amenorrhoeic women and 20 controls (age range 16-29 years) divided into four groups: group 1: 6 patients with idopathic hypogonadotrophic hypogonadism with primary amenorrhoea (IHH); group 2: 5 patients with delayed puberty owing to thalassaemia major (TM); group 3: 12 patients with secondary hypothalamic amenorrhoea (HA); group 4: 20 women with normal menses (controls). Secondary sexual characteristics had developed in all except the women with TM. Groups 1 and 2 had never menstruated and group 3 had been amenorrhoeic for 6 months to 3 years. The control group was studied during the follicular phase of the cycle. None of the patients were taking oestrogens at the time of observation. Plasma concentrations were determined for 17 beta-oestradiol (E2), deidroepiandrosterone sulphate (DHEA-S), cortisol (F), prolactin (PRL), thyroid hormones (T3 and T4), and gonadotrophins (LH and FSH). Spinal bone mineral density (BMD g/cm2) was assessed by dual photon absorbiometry. BMD (mean +/- 1SD) was reduced in the patients (group 2: 0.920 +/- 0.95; group 1: 0.980 +/- 0.94; and group 3: 1.037 +/- 0.75) as compared with the controls (1.290 +/- 0.95) (P less than 0.01). In the three groups of patients, plasma E2 levels were lower than 50 pg/ml and were positively correlated with the BMD. As expected, plasma gonadotrophin levels were highly and significantly reduced (P less than 0.01) in the patients, compared with that of the controls. These results suggest that reduced spinal BMD in hypogonadic women may be related to the lack of oestrogenic influence on bone metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)

Late deaths and second primary malignancies among long-term survivors of childhood cancer: an Italian multicentre study.

A multicentre registry of children who had been successfully removed from therapy for some common childhood cancers (Hodgkin's disease, non-Hodgkin's lymphoma, neuroblastoma, nephroblastoma, acute lymphatic leukaemia and other leukaemias) was established in Italy in 1981. The present study describes mortality and occurrence of second primary malignancies (SPMs) among 1467 children who were alive when the registry was established. Follow-up ended on December 31, 1983 for mortality and 1 year later for the occurrence of SPMs. Sixty-seven deaths were recorded, 11 of which were due to causes other than progression of the original disease. Eleven incident SPMs were identified (i.e. 3 acute myeloid leukaemias, 3 thyroid carcinomas, 1 bilateral breast carcinoma, 1 liver malignant mesenchymoma, 1 astrocytoma, 1 chondrosarcoma and 1 osteosarcoma) corresponding to an incidence rate of 2.1/1000 patient-years at risk. Anecdotal reports were collected regarding 2 further SPMs (a thyroid carcinoma and a myeloid leukaemia) as well as several benign tumours, including 2 mammary fibroadenomas.

Changes in immunoreactive beta-endorphin, methionine-enkephalin and ACTH in bone marrow cells and fluid from leukemic children.

The present study demonstrates the presence of the endogenous opioid peptides, beta-endorphin (beta-EP) and methionine-enkephalin (MET-ENK), and of ACTH in cell homogenates and interstitial fluid from sternal biopsy of leukemic children. The peptides were identified by chromatography and radioimmunoassay. In leukemic children with lymphoblastic cells present in the sternal sample, concentrations of immunoreactive (ir) beta-EP in the cell homogenate, but not in the fluid, were significantly higher than in leukemic children with normal bone marrow. In contrast, ir MET-ENK and ir ACTH did not differ between the two study groups either in the cell homogenate or in the fluid. These data suggest the presence of a complex system of opioid peptides in the cells and interstitial fluid of bone marrow of leukemic children with the highest concentrations of ir beta-EP appearing in samples collected during the active phase of the disease, and may suggest a possible role of opioid peptides as immunomodulatory substances.

The outcome of Wilms' tumor in infants. Italy 1970-79.

Thirty-four infants under 1 year of age with Wilms' tumor were diagnosed and treated in 14 Italian pediatric oncology units during 1970-79. The 3-year survival rates decreased with higher group unilateral tumors: 95% in group I Wilms' tumor, 75% in group II and 20% in group III. The survival rates for children with group I and II Wilms' tumor were similar for those who were treated with surgery and chemotherapy and those who also received postoperative radiotherapy. During 1975-79 fewer patients with group I Wilms' tumor received radiotherapy (1 of 11) than during 1970-74 (4 of 6, p less than 0.05). All these children are alive at this writing.