Combined therapy in children and adolescents with classical Hodgkin's lymphoma: A report from the SFCE on MDH-03 national guidelines.

Hodgkin's lymphoma (HL) in children and adolescents is highly curable, but children are at risk of long-term toxicity. The MDH-03 guidelines were established in order to decrease the burden of treatment in good-responder patients, and this report should be considered a step toward further optimization of treatment within large collaborative trials. We report the therapy and long-term outcomes of 417 children and adolescents treated according to the national guidelines, which were applied between 2003 and 2007 in France. The patients were stratified into three groups according to disease extension. Chemotherapy consisted of four cycles of VBVP (vinblastine, bleomycin, VP16, prednisone) in localized stages (G1/95 pts/23%), four cycles of COPP/ABV (cyclophosphamide, vincristine, procarbazine, prednisone, adriamycin, bleomycin, vinblastine) cycles in intermediate stages (G2/184 pts/44%) and three cycles of OPPA (vincristine, procarbazine, prednisone, adriamycin) plus three cycles of COPP in advanced stages (G3/138 pts/33%). Radiation therapy of the involved field was given to 97% of the patients, with the dose limited to 20 Gy in good responders (88%). With a median follow-up of 6.6 years, the 5-year event-free survival (EFS) and overall survival (OS) were 86.7% (83.1-89.7%) and 97% (94.5-98.1%), respectively. EFS and OS for G1, G2, and G3 were 98% and 100%, 81% and 97%, and 87% and 95%, respectively. Low-risk patients treated without alkylating agents and anthracycline had excellent outcomes and a low expected incidence of late effects. Intensification with a third OPPA cycle in high-risk group patients, including stage IV patients, allowed for very good outcomes, without increased toxicity.

Bronchogenic cyst of the tongue in an infant.

Bronchogenic cyst of the tongue is rare. We report the case of a 17-month baby who has a lingual lesion. MRI shows a well-defined cystic lesion. Treatment consisted of a complete resection and histology found a pseudostratified respiratory type epithelium. Only 10 pediatric cases of bronchogenic cyst of the tongue have been reported in the literature. MRI is the imaging modality of choice and treatment is always surgical. The final diagnosis is made by histology.

Magnetic resonance imaging of anatomical variants of the subtalar joint.

OBJECTIVE: To evaluate MRI with thin slices to depict anatomical variations of the subtalar and talocalcaneonavicular joints. METHODS AND MATERIALS: Ankle MRI was performed in 51 patients. The articular configurations were differentiated on sagittal T1-weighted and three-dimensional (3D) DESS images. Multiplanar reconstructions were performed. The variation in curvature of the posterior facet of the calcaneus and talus was analysed. 3D surface-rendered images of the calcaneus were obtained. All images were studied by an experienced physical therapist. RESULTS: Analysis revealed that 18 (36.7%) of the subjects had 3 distinct facets on the calcaneus. A missing anterior facet was revealed in five (10.2%) of subjects. Twenty-six (53.1%) subjects showed a fusion of the anterior and middle facets. In four cases, an articulation was found between the talus and the cuboid bone. At the posterior talocalcaneal articulation, variations were observed of the curvature of the medial side of the joint. CONCLUSIONS: The configuration of the facets of the talocalcaneal joints can be analysed on MR images. On 3D images, an articular connection was seen between the talus and the cuboid bone, as well as variations in the curvature of the posterior talocalcaneal joint. These anatomical variations may have implications for mobility and stability of the ankle.

Melanotic neuroectodermal tumor of infancy: case report and review of the literature.

Melanotic Neuroectodermal Tumor of Infancy (MNTI) is a rare but distinct neoplastic entity in infancy. Diagnosis is usually made before the age of 12 months. The common clinical presentation is a rapidly growing mass of the pre-maxillary area. Its surface is unevenly pigmented. To affirm the diagnosis a biopsy is necessary. Few cases of malignancy have been described (5% of cases). Adequate surgical excision is the treatment of choice. Recurrence rate is about 10 to 15% within 5 years. We report in this article the case of a newborn with MNTI illustrating that an R0 surgical excision can be correlated to a favourable prognosis. In this case the 5 years follow up didn't show any local or distant recurrence.

A human non-XLA immunodeficiency disease characterized by blockage of B cell development at an early proB cell stage.

We report a detailed analysis of a B cell defect affecting a patient girl born from first cousin parents, characterized by a severe non-X-linked agammaglobulinemia with a total absence of CD19- cells in the periphery. In the bone marrow, CD19 expression was also highly impaired, resulting in the absence of both B and preB compartments. By contrast, CD34+CD10+, CD34psiL+, and some CD19+CD10+ mostly CD34+ early proB cells were present, although diminished. Semiquantitative RT-PCR analysis performed on mononuclear bone marrow cells indicated that lambda-like, VpreB, Rag-1, Rag-2, and TdT transcripts expressed during proB cell stages were found at normal levels whereas E2A, CD10, Syk, Pax-5, CD19, Igalpha, Igbeta, VH-Cmu, and Vkappa-Ckappa transcripts characteristic of later stages were severely depressed. This phenotype resembles that of Pax-5 knock-out mice, but since the coding sequence of the patient Pax-5 cDNA was shown to be normal, the defect might rather result from an altered regulation of this gene. All these data indicate that the patient suffers from a new genetic defect that results in an arrest of differentiation within the proB cell compartment, i.e., earlier than X-linked agammaglobulinemia, before the onset of Ig gene rearrangements.

Secondary metabolites from Senecio burtonii (Compositae).

A cacalolide derivative named 4alpha-[2'-hydroxymethylacryloxy]-1beta-hydroxy-14-(5-->6) abeo eremophilan-12,8-olide and a shikimic acid derivative named (3'E)-(1alpha)-3-hydroxymethyl-4beta,5alpha-dimethoxycyclohex-2-enyloctadec-3'-enoate along with three known compounds, octacosan-1-ol, 3beta-hydroxyolean-12-en-28-oic acid and 3beta-acetoxyolean-12-en-28-oic acid were isolated from Senecio burtonii. Their structures and relative configurations were established on the basis of spectroscopic analysis.

Temperature dependence of the electronic spin-lattice relaxation time in a 2-iron-2-sulfur protein.

The ferredoxins are characterized by a strong temperature dependence of the electronic spin-lattice relaxation time T1. The measurement of this dependence above the liquid nitrogen temperature has been presented in earlier work [1] for the 2-iron-2-sulfur ferredoxin of the blue green alga Spirulina maxima. The different relaxation mechanisms which could be efficient in this range were briefly discussed. In the present paper, we extend the measurement of the temperature dependence of T1 to the low temperature range 1.25 to 30 K. From 1.25 K to 13 K, T1 is obtained by the saturating pulse method, whereas the continuous saturation method is used from 8 K to 30 K. The experimental conditions concerning these methods are discussed. The analysis of the temperature dependence curve over the whole range 1.25 K to 133 K shows clearly that different regions must be distinguished. For each region the possible relaxation processes and the corresponding vibrational modes are discussed.

Spectroscopic studies of the oxidation-reduction properties of three forms of ferredoxin from Desulphovibrio gigas.

Electron paramagnetic resonance spectra were recorded of three forms of Desulphovibrio gigas ferredoxin, FdI, FdI' and FdII. The g = 1.94 signal seen in dithionite-reduced samples is strong in FdI, weaker in FdI' and very small in FdII. The g = 2.02 signal in the oxidized proteins is weak in FdI and strongest in FdII. It is concluded that most of the 4Fe-4S centres in FdI change between states C- and C2-; FdI' contain both types of centre. There is no evidence that any particular centre can change reversibly between all three oxidation states. Circular dichroism spectra show differences between FdI and FdII even in the diamagnetic C2- state. The redox potentials of the iron-sulphur centres of the three oligomers (forms) are different. After formation of the apo-protein of FdII and reconstitution with iron and sulphide, the protein behaves more like FdI, showing a strong g = 1.94 signal in the reduced states.

Repeated high-dose chemotherapy followed by purged autologous bone marrow transplantation as consolidation therapy in metastatic neuroblastoma.

Among 62 children over 1 year of age at diagnosis, who were treated for stage IV neuroblastoma, 33 entered complete remission (CR) or good partial remission (GPR) after conventional therapy and received high-dose chemotherapy (HDC) with in vitro purged autologous bone marrow transplantation (ABMT) as consolidation therapy. The HDC was a combination of carmustine (BCNU), teniposide (VM-26), and melphalan. Thirty-three patients received one course of this regimen, and 18 received two courses. At present, 16 of the 33 grafted patients are alive in continuous CR, with a median follow-up of 28 months. Toxicity of this regimen was tolerable, principally marked by bone marrow depression and gastrointestinal (GI) tract complications. Four complication-related deaths were observed. Relapse post-ABMT occurred most often in the bone marrow. Under this treatment, actuarial disease-free survival is improved compared with that observed under conventional therapy.

Etoposide and carboplatin: a highly effective combination in relapsed or refractory Wilms' tumor--a phase II study by the French Society of Pediatric Oncology.

PURPOSE: Since we had previously demonstrated encouraging efficacy of etoposide in patients with relapsed or refractory Wilms' tumor (WT), the likely synergism between etoposide and platinum compounds prompted us to conduct a phase II study of a combination with carboplatin. PATIENTS AND METHODS: Twenty-six relapsed or refractory WT patients were included in a phase II study of two courses of combination etoposide 100 mg/m2/d for 5 days and carboplatin 160 mg/m2/d for 5 days, with a 21-day interval between the two courses. Initial stages were I (n = 2), II (n = 8), III (n = 6), IV (n = 6), V (n = 3), and unknown (n = 1). Sites of diseases were lung(s) (11 patients), abdomen-pelvis or liver or primary tumor (six patients), and multiple (eight patients). Histology was unfavorable in three of 26 patients. RESULTS: Complete response (CR) was documented in eight patients and partial remission (PR) in 11 (overall response rate, 73%). Stable disease (SD) was observed in five patients and progressive disease (PD) in two. Thrombocytopenia (grade IV) was the major toxicity, and platelet transfusions were required in all but two patients. Grade III anemia and grade III to IV neutropenia were seen in 19 and 23, respectively, of 25 assessable first courses. Venoocclusive disease of the liver was fatal in one child who had undergone irradiation to the whole abdomen, 8 weeks before study. CONCLUSION: Combination etoposide and carboplatin has impressive activity in refractory or relapsed WT at the cost of high-grade hematologic toxicity, especially thrombocytopenia. It is of great interest in second-line therapy, since eight of 26 patients are still alive in continuous CR (median follow-up duration, 40 months; range, 24 to 56). This combination deserves further investigation as first-line or consolidation treatment.

Childhood cancer incidence in the south-east of France. A report of the Provence-Alpes-Côte d'Azur and Corsica Regions Pediatric Cancer Registry, 1984-1991.

A prospective registration of incident cancers in childhood in two south-east regions of France since 1 January 1984 allows us to collect pertinent data on 875 cases throughout a period of 8 years. World age-standardised overall incidence rate is 137.63 cases/million/year. It is close to that reported in other white European. North American and Oceanian populations. The age-adjusted (age-standardised) relative frequency of each pathological group is: leukaemias 29.71%; central nervous system tumours 20.61%; lymphomas 12.75%; sympathetic tumours 9.03%; soft tissues tumours 7.37%; bone tumours 5.89%; kidney tumours 4.82%; epithelial tumours 3.83%; germinal and gonadal tumours 3.24%; retinoblastomas 2.11%; liver tumours 0.45% and others 0.14%. The comparison of these results with international available data shows that we record the world highest adjusted incidence rates for neuroblastomas (15.46) and rhabdomyosarcomas (7.04) and a high rate for Ewing's sarcomas (3.30); this fact will need to be confirmed by a longer period of observation, but even now the total number of cases (particularly for neuroblastoma) is high when compared with the data of other children registries which give rates for longer periods and for similar or larger populations.

CSF drug levels for children with acute lymphoblastic leukemia treated by 5 g/m2 methotrexate. A study from the EORTC Children's Leukemia Cooperative Group.

A multicenter EORTC study was conducted in children with acute lymphocytic leukemia to determine whether 5 g/m2 of methotrexate (MTX) (24 h i.v. infusion, four cycles) is an appropriate dosage for obtaining CSF drug concentrations approaching the critical cytotoxic level of 10(-6) M. A total of 193 cycles were analyzed for 58 patients. At the end of the 24 h infusion, the mean MTX serum level was 65.27 +/- 33.11 microM; the mean CSF MTX level was 1.47 +/- 1.1 microM; no significant difference in CSF MTX levels was observed between patients with (n = 20) and those without i.v. Ara-C (n = 38). The mean CSF MTX/serum MTX ratio was 0.029 +/- 0.027. CSF drug concentrations greater than or equal to 10(-6) M were achieved in 81% of the courses. The highest level was 8.4 X 10(-6) M. Only 5% of patients failed to achieve this drug concentration in at least one cycle. No significant correlation was observed between blood and CSF MTX levels. Mean CSF MTX levels were comparable from one cycle to another.

A non-XLA primary deficiency causes the earliest known defect of B cell differentiation in humans: a comparison with an XLA case.

We report a detailed comparison of B cell defects in two patients, one XLA and one non-XLA. Both had severe agammaglobulinemia with a total absence of CD19+ cells in the periphery. In the non-XLA case, CD19 expression was also highly impaired in the bone marrow, resulting in the absence of both B and preB compartments. Early proB cells were present since CD34+CD10+ and some CD19+CD10+ mostly CD34+ were identified, although diminished. By contrast, in the XLA patient the CD34+CD19+ proB cells were increased whereas the CD34-CD19+ preB cell population was low. Semi-quantitative RT-PCR analysis performed on mononuclear bone marrow cells from the non-XLA patient indicated that lambda-like, VpreB, Rag-1, Rag-2 and TdT transcripts expressed during proB cell stages were found at normal levels whereas E2A, CD10, Syk, Pax-5, CD19, Ig alpha, Ig beta, VH-C mu and V kappa-C kappa transcripts characteristic of later stages were severely depressed. By contrast in the XLA patient most of these transcripts were observed in normal amounts. The phenotype of the non-XLA patient resembles that of Pax-5 or Ig beta knock-out mice, but since the coding sequence of both cDNAs were shown to be normal, the blockage might rather result from an altered regulation of one of these genes or from defect of other genes. All these data indicate that the non-XLA patient suffers from a new genetic defect that results in an arrest of differentiation within the proB cell compartment, before the onset of Ig gene rearrangements. From all agammaglobulinemias reported so far, including XLA cases and those resulting from C mu gene defects, the non-XLA patient exhibits the earliest blockage in the B cell differentiation pathway.

Nonvalved homografts of thoracic aorta in operation for complex congenital cardiac disease.

BACKGROUND: In contrast to the wide and successful use of valved aortic and pulmonary homografts, the non-valved prolongation of the thoracic aorta for the repair of some complex congenital heart diseases has rarely been described. We present here our experience with the use of descending aorta and aortic arch homografts as non-valved conduits for the surgical repair of complex cardiac malformations in 8 patients. METHODS: One atriopulmonary conduit replacement four extraatrial cavopulmonary connections, and one intraatrial cavopulmonary repair were achieved by means of a homograft of the descending aorta with a diameter of 15 to 17 mm. Three pulmonary unifocalization procedures were carried out in 2 more patients using a curved homograft of the aortic arch with a diameter of 18 mm. Except for 1 patient, whose incompetent common atrioventricular valve was replaced with a mechanical prosthesis, all other patients were managed without anticoagulation. RESULTS: No conduit-related complications were seen during a follow-up of 18 to 42 months. One patient died perioperatively during an emergency central repair of the right ventricular outflow tract after bilateral unifocalization with arch homografts. Another patient died suddenly 4 months after cavopulmonary connection. The remaining 6 patients are currently doing well. CONCLUSIONS: Regardless of the complexity of the underlying malformations, we are encouraged to use nonvalved thoracic aortic homografts in the repair of congenital cardiac diseases because of the reduction in thrombotic, hemorrhagic, and infectious complications associated with their use; convenience in handling; and their versatility in size and shape.

Cardiac surgery with extracorporeal circulation in 23 infants weighing 2500 g or less: short and intermediate term outcome.

OBJECTIVE AND METHODS: From September 1990 to February 1997, 23 consecutive critically ill infants (12 males, 11 females) weighing 2500 g or less underwent cardiac surgery necessitating extracorporeal circulation (ECC). A retrospective study was carried out to evaluate short- and intermediate-term outcome. Mean weight at operation was 2265 g (range 1750-2500 g). Mean age at operation was 24 days. The indications for surgery were transposition of the great arteries (TGA; 7), ventricular septal defect (VSD; 4), aortic stenosis (AS; 3), univentricular heart (UVH; 2), tetralogy of Fallot (TOF; 2), interrupted aortic arch (IAA; 2), atrial septal defect (ASD; 1), atrioventicular septal defect (AVSD; 1) and total abnormal pulmonary venous return (TAPVR; 1). All patients were in NYHA class IV; 17 patients (74%) were intubated pre-operatively. RESULTS: The mean aortic cross-clamping time was 40 min. Twelve patients required deep hypothermia (<20 degrees C) with total circulatory arrest (mean duration 19 min). All patients were successfully weaned from extracorporeal circulation (ECC). Five patients left the operating room with an open sternum (mean duration before closure: 3.5 days). Mean duration of artificial ventilation was 10.6 days; of inotropic support 6.7 days and of intensive care stay 17.8 days. Severe complications were observed in 19 patients (83%): cardiac failure requiring high inotropic support (13), sepsis (7), and acute renal insufficiency (5). One patient needed a ventricular assist device. Five patients (22%) died in the intensive care unit (ICU): 2 AS with fibroelastosis, 2 IAA with VSD. and 1 UVH with pulmonary atresia. At discharge from the ICU, 7 patients were receiving no treatment. Mean duration of follow-up was 32 months (range 2-80 months). We had 2 reoperations: 1 for right ventricular outflow tract obstruction 1 year after a switch operation and 1 for mitral valve replacement 1 year after total abnormal pulmonary venous return repair (death 30 days post mitral valve replacement). Survival at I year was 73%. At the last clinical examination 16 patients were in NYHA class I. CONCLUSION: Despite the severity of pre-operative cardiac disease, early surgical repair with ECC in infants weighing 2500 g or less is feasible with tolerable mortality yet with significant early morbidity.

[Metastatic neuroblastoma: consolidation treatment with 2 courses of high-dose chemotherapy followed by a bone marrow autograft]. / Neuroblastomes métastatiques: traitement de consolidation par deux cures de chimiothérapie lourde suivies d'autogreffe médullaire.

Among 62 children over 1 year of age at diagnosis who were treated for stage IV neuroblastoma, 33 entered remission after conventional therapy. They received high-dose chemotherapy and in vitro purged bone marrow transplantation as consolidation therapy. Fifteen patients received one course and 18 two courses. At present, 16/33 grafted patients are alive in CR with a median follow-up of 28 months. Toxicity of this regimen was tolerable. Under this treatment, actuarial disease free survival is improved compared with that observed under conventional therapy.

Fourrier analysis demonstrate EEG slowing after circulatory arrest at 20 degrees C.

The electroencephalographic (EEG) monitoring in infants and children submitted to cardiac surgery under circulatory arrest (CA) and deep hypothermia (20 degrees C) (DH) is usually performed by display or record without analysis. These data disclose the reappearance of EEG activity but give no qualitative analysis of EEG recovery after CA. The electrical activity of the brain was monitored in these conditions by spectral analysis (fast Fourrier transformation with on-line processing). Spectral analysis of the EEG signal recorded during open heart surgery in nine infants and children operated under DH with, in five cases, CA is presented and discussed. The Fourrier analysis demonstrate in all patients with long CA (more than 30 min.) a spectral abnormality, namely the absence of fast activity (8-24 Hz) at least for the remainder of the operation. This abnormality was not present in operations without CA and was only transient after CA of shorter duration.

Insertion of an aortic and pulmonary homograft for simultaneous reconstruction of the left and right ventricular outflow tracts. A case report.

We present the case of the successful reconstruction in a child of a congenital cardiac malformation (tetralogy of Fallot) complicated by acquired aortic regurgitation and aneurysm formation of the left pulmonary artery due to previous endocarditis, by using an aortic homograft for reconstruction of the left ventricular outflow tract and a pulmonary homograft for reconstruction of the right ventricular outflow tract. Regarding the excellent results recently obtained with cryopreserved homografts, the many advantages of these valves compared to mechanical prostheses, we feel that aortic and or pulmonary homografts might constitute ideal biological valves for reconstruction of left and or right ventricular outflow tract in children when the presence of a congenital anomaly of the pulmonary valve renders an autograft impossible.

[Kimura's disease of the lymph node. Histology, immunohistochemistry, and differential diagnosis]. / La maladie de Kimura ganglionnaire. Histologie, immunohistochimie, et diagnostic différentiel.

Kimura's disease, a chronic inflammatory condition of unknown cause, occurs predominantly in young Asian adult men. The disease involves subcutaneous tissues and lymph nodes in the head and neck region. We report a new case occurring in a young woman. The diagnosis was made late on a retroauricular lymph node examination. Immunohistochemical study showed that B lymphoid area remained, located in the germinal center showing some fibrosis involvement, and in the subcortex. T lymphoid zones were observed in the paracortex. Strong IgE positivity was noted in germinal centers. Vessels were positive with CD31, CD34, factor VIII and smooth muscle actin antibodies. Warthin-Finkeldey cells were negative for lymphoid and macrophagic markers used in this study. Differential diagnosis is discussed.