Diagnóstico perinatal de rabdomiomas intracardiacos y esclerosis tuberosa / Perinatal diagnosis of cardiac rhabdomyomas and tuberous sclerosis

Los tumores cardiacos son poco comunes, y los más frecuentes son los rabdomiomas. Su diagnóstico puede realizarse durante la época fetal. La evolución es variable: algunos son asintomáticos y otros se manifiestan por una obstrucción al flujo o en forma de arritmia. Este tipo de tumores puede ser la clave diagnóstica de una esclerosis tuberosa. Dado el amplio espectro en su presentación, mostramos dos casos, uno de diagnóstico prenatal y otro a partir de un hallazgo en la ecocardiografía(AU)

Primary cardiac tumors are not very common. Rhabdomyomas are those most frequently reported during childhood. They can be diagnosed as early as the fetal period. The course varies; in some cases, there are no symptoms, while in others, the diagnosis is based on the presence of an obstruction to the flow or an arrhythmia. Tumors of this type can be the clue to the diagnosis of tuberous sclerosis. Because of the wide variety of presenting features, we describe two cases, one diagnosed prenatally and the other through a finding on echocardiography(AU)

Foscarnet therapy for congenital cytomegalovirus liver fibrosis following prenatal ascites.

We report on an infant with multi-system disease including liver fibrosis, right microphthalmia with cataract, interstitial pneumonitis, and hyperechoic lesions in the basal ganglia and in the periventricular and thalamic regions. Prenatal ascites with hepatomegaly concomitantly with detection of cytomegalovirus (CMV) DNA in the amniotic fluid, following recurrent maternal CMV infection, had been shown. Although CMV culture and DNA detection were negative in the urine, the infant was given foscarnet because CMV infection was demonstrated in the liver by DNA detection and immunohistochemical staining. Favorable clinical outcome and absence of CMV in the liver were subsequently shown. Our case suggests that congenital CMV disease following maternal recurrence may not be associated with disseminated infection but only with intracellular infection. The diagnosis should therefore be based on CMV detection in the involved organs. Moreover, this is the first report on the possible efficacy and safety of foscarnet for therapy of immunocompetent infants with congenital CMV disease.

Kidney transplantation in a girl with methylmalonic acidemia and end stage renal failure.

Methylmalonic acidemia (MMA) is an inborn error of organic acid metabolism that occurs in infancy with hypotonia, vomiting, dehydration, lethargy and failure to thrive and is biochemically characterized by metabolic ketoacidosis, hyperammonemia and sometimes hyperglycinemia. It results from deficiency of methylmalonyl-CoA mutase activity due to a defect in the mutase apoenzyme or to deficient function of one of the enzymes required for metabolism of its cofactor vitamin B12. Tubulointerstitial nephritis with progressive impairment of renal function is one of the most frequent long-term complications. We describe a case of a 17-year-old girl with methylmalonic acidemia unresponsive to vitamin B12 therapy. The clinical symptoms appeared at 4 months of life. She progressed into end stage renal disease and in January 1996 she started on hemodialytic treatment. In November 1996 we performed a kidney transplant. At present, urinary excretion of methylmalonic acid is normal and the renal function of the transplanted kidney is normal without any rejection episodes. We think that a kidney transplant could be a good therapeutic choice for the metabolic alterations in MMA with end stage renal disease. Indeed it would seem that the small methylmalonyl-CoA mutase activity present in the transplanted kidney could be sufficient to ensure normal metabolism of organic acids. Otherwise, the therapeutic goal can be achieved with a protein-restricted diet.

[Nutritional status disorders prevalence rates in a sample of pediatric oncology Day Hospital patients]. / Prevalenza delle alterazioni dello stato nutrizionale in un campione di pazienti afferenti a un day hospital oncologico pediatrico.

BACKGROUND: Nutritional status is more important in children than in adults because it is necessary to support normal growth and development. In industrialized countries the prevalence of nutritional status disorders in the pediatric population are as follows: 35-40% of children are overweight/obese, while the underweight status disappeared in some reports or, when it is present, it is associated with other diseases. The aim of this study was to investigate the prevalence rates of nutritional status disorders among an unselected sample of Pediatric Oncology Day Hospital patients. METHODS: Anthropometric parameters of weight and height have been measured in patients affected with solid tumor either on-therapy or off-therapy (0-24 mo). Then Real Body Weight (% RBW) was estimated referring to National Center for Health Statistic percentiles. The sample was then divided into 4 weight classes (under-weight, normal-weight, over-weight and obese) according to % RBW. RESULTS: Overweight patients (overweight + obese) were 44.4%, and 13.9% underweight. Dividing the patients according to whether they are on-therapy or off-therapy, the prevalence of overweight was 36.9% in the former group and 52.9% in the latter, and the underweight prevalence was 26.3 vs 0%. CONCLUSIONS: Our preliminary data show that in this sample of patients on treatment obesity and overweight are present in a similar percentage of the healthy population, but underweight status prevalence is 26.3%. In the sample of patients off-therapy the underweight status disappeared while the overweight status increased. These data suggest that nutritional assessment in oncologic patients is required in order to provide nutritional strategies.

Nephron-sparing surgery for unilateral primary renal tumor in children.

PURPOSE: Definition of the role of nephron-sparing surgery (NSS) in the treatment of children with primary unilateral renal tumor (URT). METHODS: Between January 1992 and June 2000, 28 children with URT were admitted to our surgical unit. Criteria for selection of patients eligible for NSS were at least 50% of affected kidney preservable and stage I at surgery (frozen section biopsies from regional lymph nodes, perirenal fat, and surrounding renal parenchyma). Preoperative 2-drug chemotherapy was given to all patients more than 6 months of age. Between 1992 and 1995, 3-drug chemotherapy was used after NSS. Thereafter, following NSS, 2-drug chemotherapy was given if no microscopic residual disease was found on final histologic examination. RESULTS: NSS was feasible in 10 of 28 children (35%). Enucleation of 6 tumors (1 metachronous) was performed in 5 patients. NSS was elective in 5 patients, mandatory in 3 patients (1 with aniridia and genitourinary anomalies, 1 with chronic glomerulonephritis, 1 with bilateral hyperplastic nephroblastomatosis), and advisable in 2 patients (1 with familial vesicoureteric reflux and 1 with cystic nephroma). Seven children had standard histology nephroblastoma, 1 highly differentiated epithelial type nephroblastoma, 1 oncocytoma, and 1 cystic nephroma. The only post-NSS complication was macroscopic hematuria in 1 patient. None of the patients had a relapse. All children are alive and disease free with good functioning of the affected kidney after NSS, at a mean follow-up of 40.7 months (range, 2 to 100 months). CONCLUSION: NSS should be considered in selected children with URT, especially in patients with increased risk for metachronous tumor or renal disease, and in patients with benign or low-grade malignant URT.

Ten-day schedule oral etoposide therapy in advanced childhood malignancies.

PURPOSE: The activity of etoposide (VP-16) has been demonstrated to be schedule-dependent. Several studies have been conducted on the efficacy and safety of different schedules of VP-16 both in adults and in children, but the optimal schedule has not been determined. METHODS: In the current study, the feasibility and effectiveness of prolonged oral VP-16 in children with high-risk malignancies were evaluated. Between April 1995 and February 1999, 15 pretreated patients with high-risk tumors received oral VP-16. The schedule of therapy was oral VP-16 50 mg/m2/day for 10 consecutive days and 1-week interval between cycles. Therapy was stopped after 1 year of treatment or at time of progressive disease or possible surgery. All patients had received parenteral VP-16 in their earlier chemotherapy. RESULTS: Twelve patients were evaluable for tumor response. After 2 to 4 months of treatment, one patient had complete remission (CR), two had partial response (PR), two had minor response (MR), two had mixed response (MxR), three had stable disease (SD), and two had progressive disease (PD). A useful palliative effect was noted in patients with stable disease. In three patients, oral VP-16 was administered for maintenance therapy. After an average follow-up of 27.5 months (range, 7-41 months), five patients are alive without disease (in three, total surgery was performed after VP-16 therapy) and three patients are alive with disease. Six patients died of progressive disease, and one died of promyelocytic leukemia. One patient had Grade 34 thrombocytopenia; in the remaining patients, no acute toxicity was observed during treatment. CONCLUSIONS: This schedule of oral VP-16 produced CRs, PRs, and MRs in medulloblastoma, neuroblastoma, teratocarcinoma, and ependymoma. Stable disease was observed in three patients, one with an Askin tumor, one with medulloblastoma, and one with hepatoblastoma. Given the possible leukemogenic risk, this schedule should be used as a palliative form of therapy or in patients with poor prognosis..

Red blood cell membrane lipid peroxidation and resistance to erythropoietin therapy in hemodialysis patients.

BACKGROUND: Chronic hemolysis, inadequate production of erythropoietin (EPO) or an impaired response of erythroid stem cells to EPO are the main factors of anemia in end-stage renal disease (ESRD) patients. Oxidative damage of red blood cell (RBC) membrane is a well-established cause of chronic hemolysis in hemodialysis (HD) patients. Administration of high-dose recombinant human EPO (rHuEPO) fails to correct anemia in 5 to 10% HD patients although all established factors of resistance to rHuEPO therapy have been previously ruled out or corrected. PATIENTS AND METHODS: We investigated the degree of RBC membrane oxidative damage in 9 HD patients who failed to respond to maximal rHuEPO administration (more than 200 UI/Kg weekly for 4 months consecutively, group A), compared to 10 patients who showed a good response to standard rHuEPO therapy (group B) and to 10 patients who needed no treatment (group C). RBC malondialdehyde (MDA) was assumed as the index of oxidative stress in erythrocyte membrane. RESULTS: No significant difference in erythrocyte MCV and MCHC, iron status, parathyroid function, aluminum and dialysis-related blood loss was observed between patients of group A, B and C. RBC MDA, reticulocyte count, plasma-free hemoglobin (fhb) and serum lactate dehydrogenase (LDH) were significantly higher while plasma haptoglobin was significantly lower in patients of group A compared to patients of groups B and C. Moreover, a significant inverse relationship was observed between RBC MDA and either plasma hemoglobin, RBC count and hematocrit when all patients were evaluated together. CONCLUSION: In conclusion, increased oxidative damage of RBC membrane is often detectable in HD patients who fail to respond to rHuEPO administration even in the absence of all established factors of resistance to EPO. Peripheral response to rHuEPO may be normal in these patients and persistent anemia may be related to enhanced hemolysis due to oxidative stress. Oxidative damage itself may therefore be considered a factor of resistance to EPO.

Hypersensitivity to carboplatin in children.

BACKGROUND: Hypersensitivity reactions are rare but at times severe complications to cytostatic drugs. PROCEDURE: The percentage of allergic reactions to carboplatin and their clinical features were evaluated in 185 children affected by different solid tumors and treated with etoposide-carboplatin chemotherapy. Allergic reactions that occurred during or immediately following etoposide infusion (5 cases, 2.8%) were excluded from the study. RESULTS: Seventeen out of 185 patients (9.2%) suffered from allergic responses to carboplatin. The first of these occurred after an average of 10.1 courses (range, 1-23; median, 9). The risk calculated according to the number of courses is 2% at 6 courses, 11.3% at 12 courses, and 47% at more than 12 courses. CONCLUSIONS: The high risk of allergic reactions to multiple courses of carboplatin should be kept in mind when developing treatment regimens that include the drug.

Metastatic medulloblastoma in 10-year-old girl treated successfully with chemotherapy without radiotherapy.

We report a case of high risk medulloblastoma with leptomeningeal intracranial and spinal metastasis in a 10-year-old girl treated successfully with conventional prolonged chemotherapy without radiotherapy. This is a particular case of medulloblastoma that at onset did not receive standard therapy for medulloblastoma i.e. neither surgery nor craniospinal irradiation. This 10-year-old Chinese girl affected with localized medulloblastoma was previously treated at a medical department in China only with radiotherapy on the posterior fossa. When the child arrived in Italy with progressed metastatic medulloblastoma, she was treated with carboplatin/etoposide association i.v. followed by oral etoposide and partial surgery of the primitive mass. The schedule of chemotherapy was etoposide 300 mg/sqm followed by carboplatin 1000 mg/sqm in one day every 21-28 days for the first six courses, then etoposide 200 mg/sqm and carboplatin 600 mg/sqm in one day every 28-35 days for further 11 courses and oral etoposide 50 mg/sqm/day for ten consecutive days and one week interval between two cycles for one year. At present the girl is alive and disease-free, and has been off-therapy for 31 months. Interestingly, in this case a long-lasting complete remission was obtained without radiotherapy and without myeloablative chemotherapy. Oral etoposide played an important role in achieving a complete remission.

Chemotherapy in low-grade astrocytoma management.

The role of chemotherapy (CHT) in the management of low-grade astrocytoma (LGA) is still unclear. Nineteen children with nonresectable symptomatic LGA were treated with carboplatin (CBDCA) and etoposide (E). There were 15 newly diagnosed cases and 4 were relapses; 6 of the children were under 5 years old. In all children radiological evaluation by CT scan and/or MRI was performed after four courses of CHT. We observed complete response (CR)+ minor response (MR) in 37% of these cases and an improvement in neurological symptoms in 63%. Radiological evaluation performed in 6 patients who received CHT for longer periods (8-12 courses) showed major responses (CR+PR) in 67%. Local radiotherapy (40 Gy) was administered after CHT in 14 cases, but in 3 of these radiotherapy was delayed for 2 years. Five patients did not receive radiotherapy. The overall survival was 58% after an average follow-up of 60 months. All patients with brain stem tumors died of progressive disease even though 3 of these had shown clinical improvement after chemotherapy. In conclusion, in the treatment of nonresectable symptomatic LGA, CHT with CBDCA associated with E can be used to postpone radiotherapy in young children and even to avoid radiotherapy in some cases.

Ceftriaxone as a single agent in empirical therapy of unexplained fever in granulocytopenic children with solid tumors.

The optimal management of fever in granulocytopenic cancer patients remains controversial. Antibiotic monotherapy is increasingly an option for the initial empiric treatment of febrile granulocytopenic patients with solid tumors. Available data show that response to empiric therapy is often more related to disease classification (solid tumors vs. acute leukemia) than to the regimen used. In this study we based empiric monotherapy on the underlying disease (solid tumors) in treating 33 episodes of fever in 26 granulocytopenic children with cancer. We investigated the potential effectiveness of single daily doses of ceftriaxone administered empirically in febrile granulocytopenic children with solid tumors. Fever was treated successfully with ceftriaxone monotherapy in 91% (30/33) of febrile episodes. None of the patients died as a result of primary infection. These results suggest that empirical monotherapy with once-daily ceftriaxone is safe and effective. In addition, when compared with other extended-spectrum cephalosporins such as ceftazidime, once-daily administration of ceftriaxone reduces cost and patient inconvenience, allowing convenient parenteral therapy even on an outpatient basis.

Use of ICRF-187 for prevention of anthracycline cardiotoxicity in children: preliminary results.

The objective of this study is to assess the efficacy of ICRF-187 as a protective agent against anthracycline cardiotoxicity. Cardiac function was evaluated by echocardiography before and after each cycle of anthracycline chemotherapy associated with ICRF-187 and compared with that of a second group receiving anthracycline chemotherapy without ICRF-187. The patients were a group of 15 consecutive children affected with various types of solid tumors who were treated with either doxorubicin-daunomycin or epirubicin (average doses 340 and 280 mg/m2, respectively), and treatment was associated with ICRF-187. A second group of 15 consecutive children affected with different malignancies were simultaneously treated with either doxorubicin-daunomycin or epirubicin (average doses 309 and 270 mg/m2, respectively), but without ICRF-187 association. None of the patients treated with anthracyclines and ICRF-187 association showed abnormalities on echocardiographic examination. In the second group of patients treated with anthracyclines but without ICRF-187 association, we observed a decrease in the left ventricular ejection fraction to < 55% and a decrease in the left ventricular fractional shortening to < 28% in two patients (13.3%). One of these (6.6%) showed a dilatative cardiomyopathy. Both groups of patients were treated with low doses of anthracyclines. Although this study was not randomized, in patients without ICRF-87 cardioprotection, there was a trend for a worse evolution with one case of clinical cardiomyopathy as well as subclinical cardiac abnormalities.

Successful management with interferon alpha-2a after prednisone therapy failure in an infant with a giant cavernous hemangioma.

A giant cavernous hemangioma of the left arm with severe thrombocytopenia and consumptive coagulopathy was observed in a neonate. Initial treatment with prednisone, platelet transfusions, and clotting replacement failed to control the bleedings. The child was then treated with daily subcutaneous infusions of interferon alpha-2a. Coagulopathy rapidly improved and transfusions were drastically reduced. The hemangioma regressed progressively and disappeared after 4 months of treatment.

Long-lasting complete remission after prolonged administration of etoposide in a child with a second recurrence of alveolar rhabdomyosarcoma.

The authors report a case of alveolar rhabdomyosarcoma (RMS) of the thigh complicated by two successive distant relapses shortly after radio- and chemotherapy, treated with etoposide, and resulting in complete long-lasting remission. The schedule of etoposide was 100 mg/ m2/d intravenously for three days weekly for 3 weeks, with an interval of 1 week between courses. This was administered for 11 months. The child is alive without disease and off therapy 20 months after completion of etoposide treatment. Preclinical studies and experience in adults have suggested that the cytotoxic effects of etoposide show a marked dependence on schedule. A divided dose regimen of single-agent etoposide has previously been shown to have activity in relapsed rhabdomyosarcoma, but the outcome or the duration of complete response has not yet been fully evaluated. In out poor-prognosis case, the prolonged administration of etoposide achieved a long-lasting complete response.

Immunohistochemical detection of p140trkA and p75LNGFR neurotrophin receptors in neuroblastoma.

In neuroblastoma, high levels of mRNA for p140trkA and p75LNGFR neurotrophin receptors are predictive of favorable outcome. Their evaluation by Northern blot, however, requires substantial amounts of tissue and this prevents their routine evaluation as well as the possibility for multicenter studies to be easily carried out. In an attempt to overcome these limitations, the feasibility and reliability of determining both neurotrophin receptors on cryostat sections by immunohistochemistry were assessed, and these findings were compared to those obtained from Northern blot analysis. Primary tumor samples from 28 untreated patients at all stages were evaluated by using H10 anti-p140trkA and ME20.4 anti-p75LNGFR mAbs. Although weak, positive immunostaining was found in 9 of 28 tumors for p140trkA and in 5 of 28 tumors for p75LNGFR. As compared to Northern blot, the concordance rate was 79% (22 of 28 cases) for p140trkA (p < 0.05) and 71% (20 of 28 cases) for p75LNGFR (p < 0.05). No case negative for Northern blot was found to be positive with immunohistochemistry. Since only high mRNA levels for both receptors have been shown to be clinically relevant, their immunohistochemical detection, although less sensitive than Northern blot, can be just as sufficient and reliable as a prognostic tool, and possibly with a better cost-benefit ratio.

Ultrasound in the management of hepatic veno-occlusive disease in three children treated with dactinomycin and vincristine.

Three children, treated with dactinomycin and vincristine without radiotherapy showed hepatic toxicity consistent with diagnostic criteria for hepatic veno-occlusive disease (VOD). Two patients were affected with Wilms' tumor and the third with malignant fibromatosis. The clinical manifestations of VOD were mild and regressed in all patients after supportive therapy. Serial ultrasonography (US) was performed in all cases and was useful in confirming the diagnosis and in evaluating the severity of the disease. US features of VOD were hepatomegaly, gallbladder wall thickening, ill-defined borders of the hepatic vessels, and ascites. Parenchymal heterogeneity was still present after several months as a result of the hepatic injury. The hazy appearance of the portal vessels and the gallbladder wall thickening seemed directly correlated with the degree of hepatic involvement in the early phase of VOD.