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OBJECTIVES: To evaluate the performance of screening for small-for-gestational-age (SGA) fetuses by ultrasound biometry at 30-35 weeks' gestation, and to determine the impact of screening on obstetric and neonatal outcomes. METHODS: For this prospective cohort study, pregnant women were recruited from two French university maternity centers between 2003 and 2006. Performance measures of third-trimester biometry for the prediction of SGA, defined as estimated fetal weight < 10(th) centile, were analyzed. Obstetric outcomes and neonatal health status were compared, first, between SGA neonates diagnosed correctly at ultrasound examination (true positive (TP); n = 45) and SGA neonates that went undiagnosed (false negative (FN); n = 110) and, second, between non-SGA neonates identified as normal at ultrasound examination (true negative (TN); n = 1641) and non-SGA neonates diagnosed incorrectly as SGA (false positive (FP); n = 101). RESULTS: In the prediction of SGA, third-trimester ultrasound had a sensitivity of 29.0% (95% CI, 22.5-36.6%) and specificity of 94.2% (95% CI, 93.0-95.2%). Positive and negative predictive values were 30.8% (95% CI, 23.9-38.7%) and 93.7% (95% CI, 92.5-94.8%), respectively. One hundred and ten SGA neonates went undiagnosed at ultrasound. Compared to the TN neonates considered as of normal weight at ultrasound, planned preterm delivery (before 37 weeks) and elective Cesarean section for a fetal growth indication were 2.4 (P = 0.01) and 2.85 (P = 0.003) times more likely to occur, respectively, in the FP group of non-SGA neonates, diagnosed incorrectly as SGA during the antenatal period. There was no statistically significant difference in 5-min Apgar score < 7, cord blood pH at birth < 7.15 and need for neonatal resuscitation between the two subgroups (TN vs FP and TP vs FN). CONCLUSIONS: The performance of third-trimester ultrasound screening for SGA seems poor, as it misses the diagnosis of a large number of SGA neonates. The consequences of routine screening for SGA in a low-risk population may lead to unnecessary planned preterm deliveries and elective Cesarean sections in FP pregnancies, without improved neonatal outcome in the FN pregnancies.
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Retardo del Crecimiento Fetal/diagnóstico por imagen , Recién Nacido Pequeño para la Edad Gestacional , Ultrasonografía Prenatal/métodos , Adulto , Cesárea , Estudios de Cohortes , Femenino , Peso Fetal , Humanos , Recién Nacido , Trabajo de Parto , Valor Predictivo de las Pruebas , Embarazo , Resultado del Embarazo , Tercer Trimestre del Embarazo , Estudios ProspectivosRESUMEN
BACKGROUND: Ovarian teratoma (OT) is the most common ovarian neoplasm in children. Oophorectomy has been the standard treatment but may impair fertility. The aim of this study was to investigate the feasibility and outcome of ovarian-sparing surgery (OSS) for OT. PROCEDURE: We retrospectively studied all children treated for OT at a pediatric teaching hospital in Paris, France, between March 1992 and July 2006. OSS was performed when deemed technically feasible in patients who had no lymphadenopathy by preoperative imaging or surgical exploration, normal tumor marker levels, and calcifications on radiographs. RESULTS: We identified 30 patients, including 29 with unilateral OT and 1 with synchronous bilateral OT. Emergent surgery was performed in five patients, among whom four had ovarian torsion requiring oophorectomy and one underwent OSS. Of the 26 OTs in the 25 remaining patients, 10 were managed with OSS and 16 with oophorectomy. Subsequently, ultrasound monitoring detected OT development in the contralateral ovary in 4 (14%) patients, after a median of 3 years (range, 1-14 years); OSS was performed in all four cases. The patient with bilateral synchronous OT, managed by OSS initially, underwent unilateral oophorectomy 3 years later for a recurrence. Overall OSS was performed for 15 (42%) OTs. CONCLUSIONS: Our results suggest recommendations for preserving fertility whenever possible without compromising the oncological prognosis. In particular, OSS should be reserved for patients who meet all criteria for localized mature teratoma. Long-term follow-up is crucial.
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Infertilidad Femenina/prevención & control , Neoplasias Ováricas/cirugía , Teratoma/cirugía , Niño , Preescolar , Femenino , Fertilidad , Estudios de Seguimiento , Humanos , Neoplasias Ováricas/complicaciones , Neoplasias Ováricas/diagnóstico por imagen , Estudios Retrospectivos , Tasa de Supervivencia , Teratoma/diagnóstico por imagen , Resultado del Tratamiento , UltrasonografíaRESUMEN
OBJECTIVES: French Guidelines on Fetal Growth Restriction (FGR) were published in December 2013. It seemed interesting to us to carry out an inventory on the management of FGR in teaching hospitals and tertiary referral centers MATERIAL AND METHODS: We carried out a retrospective survey on the academic year 2020/2021. All teaching hospitals and level III maternity in mainland France were contacted (67). The questionnaire focused on the growth curves used, the etiological assessment carried out, the rate and modalities of antenatal surveillance as well as the criteria indicating a birth. RESULTS: The response rate was 76%. The CFEF curves are used for screening in 78.4% of centers and in the event of FGR in 39.2% of them. The etiological assessment includes a referent ultrasound in 62.7% of cases and amniocentesis is offered in 74.5% of hospitals in case of severe and early FGR. All centers use umbilical Doppler for FGR. The fetal heart rate is monitored between once a week to three times a day in the event of cerebro-placental redistribution. In case of reverse flow, birth is induced from 28 weeks on for some teams while others continue the pregnancy until 39 weeks. In case of cessation of fetal growth, the expected terms of birth are between 28 and 38 weeks. CONCLUSION: There is great heterogeneity in the management of FGR, particularly in terms of antenatal surveillance and the term of birth envisaged.
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Retardo del Crecimiento Fetal , Ultrasonografía Prenatal , Femenino , Retardo del Crecimiento Fetal/epidemiología , Retardo del Crecimiento Fetal/terapia , Hospitales de Enseñanza , Humanos , Placenta , Embarazo , Estudios Retrospectivos , Encuestas y Cuestionarios , Centros de Atención TerciariaRESUMEN
Working alongside local stakeholders, members of the French-African Pediatric Oncology Group developed a 3-year program to train pediatric oncology teams from 15 French-speaking countries in Africa in using analgesics and providing palliative care. This program was rolled out in three phases: initial training, in situ assessment, and advanced training in selected topics. To access this program, multidisciplinary teams had to come up with a project to improve their existing palliative care and pain management practices, and commit themselves to implementing it. All the teams invited agreed to take part in the program, which explicitly broached a subject that is often avoided in oncology teaching. The first phase was rolled out in 2017, with 65 trainees from 19 units attending one of three sessions held in Dakar, Senegal, Abidjan, Côte d'Ivoire, and Rabat, Morocco. The subsequent assessment revealed that only half the teams had started to implement their projects. The advanced training phase was therefore adjusted accordingly. A collective training session held in Marseille was attended by 15 trainees from seven teams whose projects were already underway, while in situ mentoring was provided for six other teams, through French-African twinnings in four cases. The length and openness of the program meant that we were able to identify and share the units' diverse realities, and fine-tune their projects accordingly, as well as plan ways of continuing the training both locally and collectively.
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Educación Médica Continua/métodos , Oncología Médica/educación , Cuidados Paliativos , Grupo de Atención al Paciente , Pediatría/educación , Adolescente , África , Niño , Preescolar , Educación Médica Continua/organización & administración , Francia , Humanos , Lactante , Recién Nacido , Cooperación Internacional , Manejo del DolorRESUMEN
Inflammation and immunity may be associated with endothelial cell (EC) injury and thrombus formation. We explored the mechanisms through which a humoral immune response directed against the endothelium might promote coagulation. Using the interaction of anti-EC antibodies and complement (C) with cultured EC as a model, we studied the expression and function of tissue factor, a cofactor for factor VIIa-mediated conversion of factor X to Xa. Exposure of EC to anti-EC antibodies and C in sublytic amounts stimulated the synthesis of tissue factor over a period of 16-42 h. Cell surface expression of tissue factor activity required activation of C and assembly of the membrane attack complex, because expression was inhibited by soluble CR1 and was not detected in the absence of C8. Elaboration of tissue factor messenger RNA was observed over a period of 8-30 h and required protein synthesis. Expression of tissue factor was not a direct consequence of the action of C on the EC but was a secondary response that required as an intermediate step the release of interleukin 1 alpha, an early product of the EC response to C activation. These findings suggest that, after the assembly of membrane attack complex on EC, the production of tissue factor and initiation of coagulation in a blood vessel depend on the production of interleukin 1 alpha and on its availability to stimulate affected EC.
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Proteínas del Sistema Complemento/metabolismo , Endotelio Vascular/metabolismo , Tromboplastina/metabolismo , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Células Cultivadas , Cicloheximida/farmacología , Cartilla de ADN/química , Expresión Génica , Interleucina-1/metabolismo , Datos de Secuencia Molecular , Inhibidores de la Síntesis de la Proteína/farmacología , ARN Mensajero/genética , Porcinos , Tromboplastina/genéticaRESUMEN
BACKGROUND: Children with WT1 gene-related disorders such as Denys-Drash syndrome (DDS) and Frasier syndrome (FS) are at increased risk of Wilms tumor and end-stage renal disease. We investigated whether Wilms tumors in these patients displayed a specific phenotype or behavior and whether nephron-sparing surgery was beneficial. PROCEDURE: We retrospectively studied all patients with DDS, FS, or other WT1 mutations treated at our institutions between 1980 and 2007. RESULTS: We identified 20 patients, of whom 18 had benign or malignant tumors. Wilms tumors occurred in 15 patients, being unilateral in 10 and bilateral in 5 (20 tumors). Median age at Wilms tumor diagnosis was 9 months. No patients had metastases. According to the International Society of Pediatric Oncology Working Classification, there were 19 intermediate-risk tumors and one high-risk tumor; no tumor was anaplastic. In patients with nephropathy who underwent unilateral nephrectomy for Wilms tumor or nephron-sparing surgery for bilateral Wilms tumor, mean time to dialysis was 11 or 9 months, respectively. Other tumors included three gonadoblastomas (in two patients), one retroperitoneal soft-tissue tumor, and one transitional cell papilloma of the bladder. Two patients, both with stage I Wilms tumor, died from end-stage renal disease-related complications. The median follow-up time for the 18 survivors was 136 months (range, 17-224 months). CONCLUSION: Most Wilms tumors in children with WT1-related disorders were early-stage and intermediate-risk tumors, with a young age at diagnosis. In patients without end-stage renal disease, nephron-sparing surgery should be considered for delaying the onset of renal failure.
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Síndrome de Denys-Drash/terapia , Síndrome de Frasier/terapia , Tumor de Wilms/terapia , Adolescente , Niño , Preescolar , Síndrome de Denys-Drash/complicaciones , Manejo de la Enfermedad , Síndrome de Frasier/complicaciones , Humanos , Fallo Renal Crónico/prevención & control , Nefrectomía , Estudios Retrospectivos , Tumor de Wilms/complicaciones , Adulto JovenRESUMEN
Ovarian sex cord-stromal tumors are rare tumors that originate from the nongerminal cells of ovary. Two decades ago, the identification of juvenile granulosa-cell tumors (GCT), as a specific entity inside this group, allowed a better treatment of these tumors in children. However, little data have been reported on the natural course of the disease and reliable prognostic factors have not been yet defined. We here review the clinical and genetics aspects of granulosa tumors, based on a series of 40 children. This national collaborative study involved the French Society of Children Cancer and eight clinical departments of pediatric endocrinology. We found that early diagnosis of a tumor, revealed by clinical signs of hyperoestrogeny, is an important prognostic factor. The pathophysiology of these tumors is still debatable and several cellular- and molecular-abnormal signals could be implicated in their development. The role of growth factors and oncogenes through the signaling pathway of MAP kinase is still discussed. According to our data, FSH signaling-transduction pathway, such as a constitutionally activated Galphas, could also be implicated in the induction of granulosa cell proliferation and seems to modulate the invasiveness of the tumor. Last, we have described a low-expression pattern or an extinction of an ovarian-determination gene, FOXL2, which is related to a worse prognosis of this tumor.
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Factores de Transcripción Forkhead/análisis , Tumor de Células de la Granulosa/patología , Células de la Granulosa/patología , Neoplasias Ováricas/patología , Adolescente , Factores de Edad , Niño , Preescolar , Femenino , Proteína Forkhead Box L2 , Factores de Transcripción Forkhead/genética , Factores de Transcripción Forkhead/fisiología , Tumor de Células de la Granulosa/fisiopatología , Tumor de Células de la Granulosa/cirugía , Tumor de Células de la Granulosa/terapia , Células de la Granulosa/metabolismo , Humanos , Neoplasias Ováricas/fisiopatología , Neoplasias Ováricas/cirugía , Neoplasias Ováricas/terapia , PronósticoRESUMEN
A. Delarue, C. Bergeron, F. Mechinaud-Lacroix, C. Coze, M. Raphael, C. Patte, pour le « Comité Lymphome ¼ de la SFCE Over the past two decades, dramatic improvements in the treatment of children with Non-Hodgkin's Lymphoma have led to cure rates close to 90%, even in advanced-stage disease. The most frequent localization is abdominal, where Burkitt or Burkitt-like subtypes are predominant. Initial management often occurs in the setting of a urgent surgical intervention where multiple complications may gravely threaten prognosis within days or even hours. The SFCE Lymphoma Committee's guidelines for optimal management include: 1) The diagnosis of lymphoma should be systematically evoked whenever the clinical context is not consistent with idiopathic intussusception, particularly in children over the age of 3 or when clinical and/or ultrasound findings are not typical; 2) Limited bowel resection should be performed only if it allows complete tumor removal and is technically simple without extensive dissection or risk of major complications; 3) If surgical resection is likely to be difficult, risky, or incomplete, surgery should be limited to sampling of peritoneal fluid and tumor; 4) In all cases, adequate tissue should be obtained and sent to the pathology department in appropriate media Analysis of tumor material may require, in addition to histology and cytology, immunophenotyping, cytogenetics, and molecular biology studies in order to arrive at an accurate diagnosis and prognosis and to guide treatment choices.
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Over the past two decades, dramatic improvements in the treatment of children with Non-Hodgkin's Lymphoma have led to cure rates close to 90%, even in advanced-stage disease. The most frequent localization is abdominal, where Burkitt or Burkitt-like subtypes are predominant. Initial management often occurs in the setting of a urgent surgical intervention where multiple complications may gravely threaten prognosis within days or even hours. The SFCE Lymphoma Committee's guidelines for optimal management include: 1) The diagnosis of lymphoma should be systematically evoked whenever the clinical context is not consistent with idiopathic intussusception, particularly in children over the age of 3 or when clinical and/or ultrasound findings are not typical; 2) Limited bowel resection should be performed only if it allows complete tumor removal and is technically simple without extensive dissection or risk of major complications; 3) If surgical resection is likely to be difficult, risky, or incomplete, surgery should be limited to sampling of peritoneal fluid and tumor; 4) In all cases, adequate tissue should be obtained and sent to the pathology department in appropriate media Analysis of tumor material may require, in addition to histology and cytology, immunophenotyping, cytogenetics, and molecular biology studies in order to arrive at an accurate diagnosis and prognosis and to guide treatment choices.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Intestinales/tratamiento farmacológico , Neoplasias Intestinales/cirugía , Linfoma no Hodgkin/tratamiento farmacológico , Linfoma no Hodgkin/cirugía , Guías de Práctica Clínica como Asunto , Dolor Abdominal/etiología , Quimioterapia Adyuvante , Niño , Medicina Basada en la Evidencia , Francia , Humanos , Neoplasias Intestinales/complicaciones , Neoplasias Intestinales/diagnóstico , Linfoma no Hodgkin/complicaciones , Linfoma no Hodgkin/diagnóstico , Sociedades Médicas , Resultado del TratamientoRESUMEN
PURPOSE: In adults' non-seminomatous germ cell tumours (NS-GCT), alpha-fetoprotein (AFP) decline was identified as an important prognostic factor. We investigated its prognostic value in the French TGM95 study for childhood NS-GCT. PATIENTS AND METHODS: Three risk groups were defined: low risk (LR: localised and completely resected pS1, AFP<15000 ng/ml), with a 'wait-and-see' strategy; intermediate-risk (IR: localised incompletely resected, AFP<15000 ng/ml) with 3-5 vinblastine-bleomycine-cisplatin courses; high risk (HiR: AFP≥15000 ng/ml and/or metastatic) with 4-6 etoposide-ifosfamide-cisplatin courses. The multivariable prognostic analysis for progression-free survival (PFS) included age (±10 years), primary tumour site (1-testis, 2-ovary, 3-extragonadal), extent of disease (1-pS1, 2-loco-regional dissemination, 3-metastasis) and AFP (±10,000 ng/ml). AFP decline prognostic value was investigated in IR + HiR groups using predicted time to normalisation (TTN), AFP change, and difference between observed and expected (based on AFP half-life) area under the curve (O-E AUC). RESULTS: From January 1995 to December 2005, 239 patients (median age = 3years, 60 LR, 65 IR, 114 HiR) were included. Main sites were testis (n = 66), ovary (n = 77) and sacrococcygeal (n = 57). Five-year PFS and OS were 85% (95% confidence interval [CI] = 80-89%) and 93% (89-95%), respectively. Age ≥ 10 years (hazard ratio [HR] = 4.6, 95% CI = 2.1-10.1, p = 0.0001) and extragonadal primary (HR = 6.3, 95% CI = 2.0-19.9, p = 0.005) were significant prognostic factors. In AFP decline analysis (n = 151, 17 events), TTN (p = 0.61) and AFP change (p = 0.10) were not prognostic, whereas we showed a significant effect of O-E AUC (HR = 2.1, 95% CI = 1.0-4.2, p = 0.05). CONCLUSION: Age ≥ 10 years and extragonadal tumours remain as poor prognostic factors. Contrary to adults, TTN is not reliable in paediatric NS-GCT. The prognostic value of O-E AUC should be investigated in larger studies.
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Neoplasias de Células Germinales y Embrionarias/diagnóstico , alfa-Fetoproteínas/metabolismo , Adolescente , Edad de Inicio , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/sangre , Niño , Preescolar , Regulación hacia Abajo , Femenino , Francia/epidemiología , Humanos , Lactante , Recién Nacido , Masculino , Neoplasias de Células Germinales y Embrionarias/sangre , Neoplasias de Células Germinales y Embrionarias/epidemiología , Neoplasias de Células Germinales y Embrionarias/terapia , Pronóstico , Análisis de Supervivencia , alfa-Fetoproteínas/análisisRESUMEN
The most appropriate treatment for lymphoblastic lymphomas (LL) remains uncertain. We treated 27 patients with newly diagnosed LL according to an LMT-89 protocol, which is a modified version of the LMT-81 protocol previously reported in pediatric patients. The median age was 31 years. Mediastinal enlargement was present in 25/27 patients, with pleural effusion in 12. Four patients had central nervous system involvement and 12 had bone marrow involvement and 24/27 (89%) had advanced Ann Arbor stage III-IV disease. Complete remission (CR) was achieved in 20/27 patients, unconfirmed complete remission in three patients (residual mediastinal lesion on computed tomography scan) and four failed induction therapy (ORR: 85%). Twelve patients (44%) remained in continuous CR with a median follow-up of 95 months. Survival at 3 years (when all the events occurred in our series) was 63%. Bone marrow involvement was associated with a poor outcome. Overall survival was 85+/-20% in patients without bone marrow involvement compared to 37+/-30% in patients with bone marrow involvement. The Ann Arbor stage, age and serum lactate dehydrogenase level did not influence outcomes. This LMT-89 protocol is a safe regimen and is highly effective in advanced LL without bone marrow involvement.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Leucemia-Linfoma de Células T del Adulto/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Médula Ósea/patología , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Relación Dosis-Respuesta a Droga , Femenino , Estudios de Seguimiento , Humanos , Leucemia-Linfoma de Células T del Adulto/diagnóstico , Leucemia-Linfoma de Células T del Adulto/patología , Masculino , Persona de Mediana Edad , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/patología , Valor Predictivo de las Pruebas , Pronóstico , Inducción de Remisión , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
The childhood cancer survival rate is currently 75% in industrialized countries. Rates in developing countries are much lower. The Franco-African Childhood Cancer Group (French acronym, GFAOP) was founded in 2000 with aim of reducing this unfavorable situation in Africa. The GFAOP has developed two forms of action. The main form consists of organizing two- to twelve-month training sessions for physicians and nurses in France and Morocco. The other form involves assessing the feasibility of modern treatment protocols for various cancers in Africa. The first feasibility trials were carried out on nephroblastoma and Burkitt's lymphoma in 12 pilot units in North Africa, West Africa, and Madagascar. In the first study from 2001 to 2005 we treated 306 cases of Burkitt's lymphoma using French LMB protocols adapted to the African setting and achieved a survival rate of 61%. A second study started in 2005 using Endoxan alone achieved a highly satisfactory survival rate of 73% for neuroblastoma in all stages except bilateral. Altogether from 2001 to 2007 more than 1000 cases of nephroblastoma and Burkitt's lymphoma were treated in African hospitals by African doctors and nurses. No patients were transferred to Europe. The GFAOP supplied drugs when necessary and took care of most travel expenses. African and French doctors worked together on protocol design, trial management, and data analysis. These promising results show that the latest therapeutic techniques can be used to treat childhood cancer in Africa by adapting the protocol to conditions in developing countries. Sanofi-Aventis Laboratories in association with the International Union against Cancer has launched a major campaign to improve Pediatric Oncology in developing countries. Projects in four GFAOP units are being financed through this campaign. In 2006 the GFAOP began assessment of two new treatment protocols, i.e., one for acute lymphoblastic leukemia and the other for Hodgkin's disease. Two other projects are being planned, i.e., one for treatment of retinoblastoma and the other for treatment of some types of brain tumors.
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Cooperación Internacional , Neoplasias/terapia , África , Niño , Protocolos Clínicos , Países en Desarrollo , Francia , HumanosRESUMEN
This article describes the survival after childhood acute leukaemia (AL) and non-Hodgkin's lymphoma (NHL) of French population aged less than 15 years. The French National Registry of Childhood Leukaemia and Lymphoma recorded 3995 cases of acute lymphoblastic leukaemia (ALL), 812 of acute myeloid leukaemia (AML) and 1137 of NHL over the period from 1990 to 2000. Overall survival rates at 5 years were 82% (95% CI 80-83), 58% (95% CI 54-61) and 87% (95% CI 85-89) for ALL, AML and NHL, respectively. Survival after AL increased from 77% (95% CI 75-80) in 1990-1992 to 85% (95% CI 83-87) in 1997-2000 for ALL and from 47% (95% CI 41-54) to 61% (95% CI 55-67) for AML. Among AL cases, children aged 1-4 years had the most favourable prognosis. Down's syndrome was associated with poor survival after ALL. No gender-related variations in survival were in evidence. The results reported herein are similar to those reported by other European registries and clinical trials.
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Linfoma no Hodgkin/mortalidad , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidad , Adolescente , Antineoplásicos/uso terapéutico , Niño , Preescolar , Ensayos Clínicos como Asunto , Síndrome de Down/mortalidad , Femenino , Francia/epidemiología , Humanos , Lactante , Recién Nacido , Linfoma no Hodgkin/tratamiento farmacológico , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Tasa de SupervivenciaRESUMEN
BACKGROUND: Colony-stimulating factors promote the proliferation of certain bone marrow cell populations. The primary objective of treating patients with these factors prophylactically following chemotherapy is to reduce the risk of infection, thereby minimizing the need for hospitalization and parenteral antibiotics. The use of colony-stimulating factors in children is widespread, despite the absence of conclusive supportive data and the high cost of these drugs. Consequently, the cost-benefit ratio of using prophylactic colony-stimulating factors is an important issue in cancer therapy. METHODS: During the period from January 1994 through June 1996, 149 afebrile children with newly diagnosed non-Hodgkin's lymphoma were randomly assigned either to receive granulocyte colony-stimulating factor (G-CSF) (lenograstim; 5 microg/kg body weight per day subcutaneously) or not to receive it (the control) at the end of the first two courses of induction chemotherapy with cyclophosphamide, vincristine, prednisone, doxorubicin, and methotrexate. A cost-minimization analysis was performed to assess the cost of chemotherapy in each group and to quantify how much could be economized by prescribing G-CSF. RESULTS: The total cost for induction chemotherapy was $29,765 in the G-CSF-treated group and $30,774 in the control group, indicating that the treatment strategy with G-CSF was slightly less expensive than the strategy without G-CSF (mean difference = $1009; 95% confidence interval = -$1474 to $3492). CONCLUSION: Treatment with G-CSF following chemotherapy in children with non-Hodgkin's lymphoma--previously shown to be of limited clinical benefit--also does not appear to reduce the costs of chemotherapy.
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Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/economía , Factor Estimulante de Colonias de Granulocitos/economía , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Linfoma no Hodgkin/tratamiento farmacológico , Linfoma no Hodgkin/economía , Neutropenia/economía , Neutropenia/terapia , Niño , Preescolar , Control de Costos , Análisis Costo-Beneficio , Francia , Humanos , Neutropenia/inducido químicamente , Inducción de Remisión , Resultado del TratamientoRESUMEN
The three Andean states of Mérida, Táchira, and Trujillo in Venezuela produce tomatoes (Lycopersicon esculentum) year-round with a high frequency of virus-like symptoms. Polymerase chain reaction amplification using degenerate primers detected begomoviruses in 18% of leaf samples collected from tomato plants showing virus-like symptoms in commercial fields in these states between 1993 and 1994. A comparison of the sequences of the amplified DNA products revealed a diversity of begomovirus sequences in tomato plants from this region. Partial A component sequences (approximately 1,100 bp) clustered in four groups based on BLAST, GAP, phylogenetic analyses of the nucleic acid sequences, and comparisons of iteron sequences with known begomoviruses. Two groups of sequences were closely related to Potato yellow mosaic virus-Venezuela strain tomato and Tomato Venezuela virus, respectively, begomoviruses previously reported from other Venezuelan states. The other two groups of sequences appear to belong to two new begomovirus species.
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BACKGROUND: Interaction of complement with endothelial cells (ECs) underlies the development of inflammation and coagulation in disease. Assembly of the membrane attack complex (MAC) of complement on EC membrane, like stimulation with cytokines, upregulates tissue factor and cyclooxygenase-2 but does so via the intermediary action of IL-1alpha. We asked whether the MAC activates porcine aortic and microvascular ECs in a global manner by this mechanism and whether this mechanism is used by membrane pore-forming structures. METHODS AND RESULTS: Exposure of ECs to complement caused upregulation of mRNAs for E-selectin, intracellular adhesion molecule-1, vascular cell adhesion molecule-1, Ikappa-Balpha, interleukin (IL)-1alpha, IL-1beta, IL-8, and plasminogen activator inhibitor-1 over a period of 6 hours. The expression of these genes was not a primary response to stimulation, however, because IL-1 receptor antagonist inhibited expression of these genes. Activation of ECs by complement depended on the autocrine action of IL-1alpha, because complement-mediated EC activation was inhibited by anti-IL-1alpha antibodies. Melittin and mastoparan, amphiphilic pore-forming peptides like the MAC, induced E-selectin through intermediary action of IL-1. CONCLUSIONS: These findings suggest that transmembrane pore-forming proteins, as a class of molecules, activate ECs through the autocrine effects of IL-1alpha.
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Complejo de Ataque a Membrana del Sistema Complemento/metabolismo , Endotelio Vascular/citología , Interleucina-1/metabolismo , Proteínas de la Membrana/metabolismo , Animales , Activación de Complemento/fisiología , Selectina E/metabolismo , Cinética , ARN Mensajero/metabolismo , Porcinos , Regulación hacia ArribaRESUMEN
PURPOSE: Prognostic factors were studied in children older than 1 year who were treated with chemotherapy for extracranial localized malignant non seminomatous germ cell tumors. PATIENTS AND METHODS: Data from two consecutive protocols were pooled. The TGM 85 (1985-1989) protocol consisted of alternating courses of cyclophosphamide, dactinomycin and vinblastine, bleomycin, and cisplatin at a dose of 100 mg/m(2) per course. The TGM 90 (1990-1994) protocol was initiated with carboplatin 400 mg/m(2) substituted for cisplatin as the only modification to the previous protocol. RESULTS: We examined alpha-fetoprotein (AFP) levels, disease stage, and primary site and identified three prognostic groups. Patients with a poor prognosis had either an AFP level >/= 10,000 ng/mL or stage III disease and a sacrococcygeal or mediastinal primary site; such patients represented 46% of the patient population and experienced a 43% 3-year failure-free survival rate and a 77% overall survival rate. Patients with a good prognosis had an AFP level less than 10,000 ng/mL, stage I or II disease, and a testicular, ovarian, perineal, or retroperitoneal primary site; such patients represented 22% of the patient population and experienced no treatment failures. The other patients were classified in the intermediate prognosis group and represented 37% of the patient population, with an 81% 3-year failure-free survival rate and a 92% overall survival rate. CONCLUSION: Initial AFP level, disease stage, and primary site are the most important prognostic factors in this analysis. Prognostic models for pediatric germ cell tumors should allow the stratification of patients for a risk-adapted approach to treatment.
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Antineoplásicos/uso terapéutico , Germinoma/tratamiento farmacológico , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor/análisis , Distribución de Chi-Cuadrado , Niño , Preescolar , Gonadotropina Coriónica/análisis , Supervivencia sin Enfermedad , Esquema de Medicación , Femenino , Germinoma/mortalidad , Germinoma/patología , Humanos , Lactante , Masculino , Valor Predictivo de las Pruebas , Pronóstico , Modelos de Riesgos Proporcionales , Análisis de Supervivencia , Resultado del Tratamiento , alfa-Fetoproteínas/análisisRESUMEN
Sixteen children with non-Hodgkin's lymphoma (NHL) who had relapsed were treated with high-dose chemotherapy with BCNU, cyclophosphamide, cytarabine, 6-thioguanine (high-dose chemotherapy [HDC]) and autologous bone marrow transplantation (ABMT). Eleven complete responses were obtained and five patients remain in prolonged complete unmaintained remission 77+ to 152+ weeks after treatment. The best results were obtained in patients with CNS involvement and when this regimen was used after complete remission or partial response was obtained by other means. The results appear to be better in B-cell than in T-cell lymphomas, but the numbers are too small for statistical assessment. The use of ABMT rendered the pancytopenic period short and safe, despite the use of drug doses higher than those previously described for this HDC. The frequency of interstitial pneumonitis, possibly related to pulmonary toxicity of chemotherapy, remains a major concern. These results show that this regimen can help to cure some patients but its toxicity prohibits its use in primary therapy.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Linfoma/tratamiento farmacológico , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Trasplante de Médula Ósea , Carmustina/administración & dosificación , Niño , Preescolar , Ciclofosfamida/administración & dosificación , Citarabina/administración & dosificación , Femenino , Humanos , Masculino , Neoplasias del Sistema Nervioso/tratamiento farmacológico , Recurrencia , Tioguanina/administración & dosificaciónRESUMEN
Twenty children with advanced, nonleukemic malignancies entered a phase II study of high-dose busulfan-cyclophosphamide followed by bone marrow transplantation (BMT). All had disease refractory to conventional and/or high-dose chemotherapy (HDC). There were ten neuroblastoma patients, six non-Hodgkin's lymphoma, three Ewing's sarcoma, and one rhabdomyosarcoma. Eight had primarily resistant disease, ten were in second progressive relapse, and two in third progressive relapse. One patient was not evaluable for response. Among the 19 evaluable patients the responses observed were complete response (CR), seven; partial response (PR), three; objective effect, five; and failure, four. However, survival was poor: 15 patients died, two are alive with disease, and three are alive with no evidence of disease (NED) at 8+, 11+, 14+ months post-BMT. Toxicity was high but considered as acceptable, taking into account the terminal state of these patients. Seven treatment-related deaths were observed. This combination therapy proved to be highly effective, with a response rate of 50%, and its value for eradication of residual disease in less advanced patients should be investigated.