A single enhanced phase is sufficient for the initial computed tomography evaluation of retroperitoneal tumors in children.

PURPOSE: The goal of this study was to evaluate the incremental value of unenhanced phase in the initial evaluation of retroperitoneal tumors in children by comparison with an enhanced phase alone using computed tomography (CT). MATERIALS AND METHODS: A total of 53 patients (26 girls, 27 boys) with a total of 53 tumors who had CT examination of the abdomen and pelvis for the initial assessment of retroperitoneal tumor were retrospectively included. All CT examinations were obtained with an unenhanced set of CT images and a set of CT images obtained after intravenous administration of iodinated contrast material. One junior and one senior radiologist independently evaluated the two sets in two separate reading sessions. CT images were analyzed for tumor calcifications, tumor location, vascular encasement, local invasion and tumor content. RESULTS: Calcifications were present in 24/53 tumors (45%). On the enhanced set, the senior radiologist was able to detect calcifications in 22/24 tumors (92%) and the junior radiologist in 20/24 tumors (83%), yielding sensitivities of 92% and 83%, and specificities of 96.5% and 100%, respectively. Inter-observer agreement was excellent (Kappa=0.89). Tumor location was correctly determined by the senior radiologist in 53/53 tumors (100%) and 37/53 tumors (70%) by the junior radiologist. Using the unenhanced set, the senior radiologist was able to assess vascular encasement in 26/53 tumors (49%) against 21/53 (39%) for the junior radiologist. For tumor content, agreement between the enhanced and combined unenhanced and enhanced CT was 77% for both radiologists. CONCLUSION: Enhanced CT performs as well as unenhanced CT for evidencing calcifications and is therefore sufficient for the initial assessment of retroperitoneal tumor in children.

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.

A novel, objective, quantitative method of evaluation of the back pain component using comparative computerized multi-parametric tactile mapping before/after spinal cord stimulation and database analysis: the "Neuro-Pain't" software.

INTRODUCTION: One of the major challenges of neurostimulation is actually to address the back pain component in patients suffering from refractory chronic back and leg pain. Facing a tremendous expansion of neurostimulation techniques and available devices, implanters and patients can still remain confused as they need to select the right tool for the right indication. To be able to evaluate and compare objectively patient outcomes, depending on therapeutical strategies, it appears essential to develop a rational and quantitative approach to pain assessment for those who undergo neurostimulation implantation. OBJECTIVES, MATERIAL AND METHODS: We developed a touch screen interface, in Poitiers University Hospital and N(3)Lab, called the "Neuro-Pain'T", to detect, record and quantify the painful area surface and intensity changes in an implanted patient within time. The second aim of this software is to analyse the link between a paraesthesia coverage generated by a type of neurostimulation and a potential analgesic effect, measured by pain surface reduction, pain intensity reduction within the painful surface and local change in pain characteristics distribution. The third aim of Neuro-Pain'T is to correlate these clinical parameters to global patient data and functional outcome analysis, via a network database (Neuro-Database), to be able to provide a concise but objective approach of the neurostimulation efficacy, summarized by an index called "RFG Index". RESULTS AND DISCUSSION: This software has been used in more than 190 patients since 2012, leading us to define three clinical parameters grouped as a clinical component of the RFG Index, which might be helpful to assess neurostimulation efficacy and compare implanted devices. CONCLUSION: The Neuro-Pain'T is an original software designed to objectively and quantitatively characterize reduction of a painful area in a given individual, in terms of intensity, surface and pain typology, in response to a treatment strategy or implantation of an analgesic device. Because pain is a physical sensation, which integrates a psychological dimension, its assessment justifies the use of multidimensional and global evaluation scales. However, in the context of neurostimulation and comparative clinical trials designed to test the technical efficacy of a given device, a simple, objective and quantitative evaluation tool could help to guide tomorrow's treatment options by transforming personal convictions into a more robust scientific rationale based on data collection and data mining techniques.

The use of computed tomography and nuclear medicine examinations in paediatric oncology: An analysis of practice in a university hospital.

PURPOSE: The purpose of this study is to evaluate, in terms of number of examinations and how effective doses are distributed by location and chronology, the use of CT and nuclear medicine examinations in the management of paediatric oncology patients. MATERIALS AND METHODS: This was a retrospective and descriptive study that included 57 children (13 with neonatal neuroblastoma, 18 with renal tumours, and 26 with lymphoma) over a 5-year period, with the length of monitoring ranging from 1 to 7 years. All CT scans and nuclear medicine examinations were counted, and the effective doses calculated. RESULTS: The majority of the examinations were performed during the first year of management. The cumulative effective doses ranged from 7-152 mSv. The lymphoma group received the highest doses, but fewer than 10% of children received in excess of 100 mSv, as against 40% in the North American study published by Chawla et al. CONCLUSION: The usage of irradiating diagnostic radiological examinations in paediatric oncology produces considerable effective doses, which must lead us to consider evaluating our practices, exploring all possible ways to improve protection from radiation, especially in terms of justifying investigations and using alternatives.

Usefulness of corticosteroid therapy during chronic disseminated candidiasis: case reports and literature review.

OBJECTIVES: Chronic disseminated candidiasis (CDC) is a disseminated fungal infection that is frequently seen in patients undergoing intensive treatment of haematological malignancies. The first signs of CDC appear during neutrophil recovery. Clinical and physiopathological characteristics of CDC suggest it belongs to the spectrum of fungus-related immune reconstitution inflammatory syndrome (IRIS). We report five cases of CDC treated with antifungal therapy and adjuvant corticosteroids to decrease the exacerbated inflammatory response. METHODS: We conducted a retrospective study in the Haematology Department of the University Hospital of Tours, France. The five reported cases were treated for CDC with antifungal therapy and adjuvant corticosteroids. RESULTS: Of the five cases of CDC, one was proven and four were possible, according to the 2008 European Organization for Research and Treatment of Cancer (EORTC) classification. All patients were being treated for acute leukaemia. In all cases, symptoms disappeared 2.8 days (range, 1-7) after the beginning of adjunctive corticosteroid therapy. Corticosteroids were administered on average for 146 days (range, 4 weeks-1 year) and antifungal therapy was administered for the duration of chemotherapy consolidation. There was no exacerbation of CDC symptoms during the next round of chemotherapy or bone marrow transplantation. One patient died from relapse of leukaemia. CONCLUSIONS: Within the framework of IRIS, adjuvant corticosteroid therapy could rapidly improve CDC symptoms and allow continued chemotherapy without delay and without compromising the haematological prognosis.

Effect of coadministered HIV-protease inhibitors on tacrolimus and sirolimus blood concentrations in a kidney transplant recipient.

A patient with human immunodeficiency virus infection and end-stage renal disease received a renal transplant. At the time of surgery, the patient was on quadruple antiretroviral therapy (lamivudine, zidovudine, and amprenavir/ritonavir). Immunosuppression was initiated with basiliximab, corticosteroid, mycophenolate mofetil, and a single 0.5 mg dose of tacrolimus. In the following days, an increase in tacrolimus concentration was observed with a peak of 37 ng/mL. Tacrolimus half-life was 6.5 days and tacrolimus maintenance dose was 0.5 mg every 4 days. Eleven months later, the patient had developed Kaposi sarcoma. Tacrolimus was replaced by sirolimus (first dose 1 mg), and the patient was stabilized with 1.5 mg of sirolimus once a week. Increased tacrolimus half-life and increased dose interval of sirolimus and tacrolimus were due to CYP3A4/5 and/or P-glycoprotein inhibition by protease inhibitors. Close monitoring is required in the management of tacrolimus and sirolimus dosing regimens when combined with ritonavir boosted HIV-1 protease inhibitors.

[Evans' syndrome: a retrospective study from the ship (French Society of Pediatric Hematology and Immunology) (36 cases)]. / Syndrome d'Evans: étude rétrospective de la société d'hématologie et d'immunologie pédiatrique (36 cas).

UNLABELLED: Evans' Syndrome (ES) is defined as the combination of immune thrombocytopenia (ITP) and autoimmune haemolytic anemia (AIHA), in the absence of any known underlying etiology. Pathophysiology, epidemiology and outcome remain unclear. POPULATION: Thirty-six children (20 male, 16 female), who were diagnosed in the SHIP french centres (Société d'hématologie et d'immunologie pédiatrique) between 1990 and 2002 with ES, were included in this retrospective study. RESULTS: Median age at diagnosis was 4 years. In 21 children, ES occurred in the setting of consanguinity, family history of autoimmune/inflammatory disease, associated autoimmune disorder or immunoregulatory abnormalities (serum imunoglobulins, peripheral blood lymphocytes subsets, low level of the C3-C4 complement components, nuclear antibodies). Several successive treatments were used in this serie (median: 3, range: 0-10) including corticosteroid therapy (35/36), intravenous immunoglobulins (32/36), immunosuppressive agents (14/36), splenectomy (9/36) and anti CD 20 monoclonal antibodies (6/36). Patients with a low level of serum immunoglobulins were more often non-responders to corticosteroidtherapy/intravenous immunoglobulins and required more frequently further therapy (P=0.03). Three patients died (intracranial bleeding, N=2, Guillain-Barre syndrome; N=1). CONCLUSION: ES was a severe, life-threatening disease, requiring aggressive immunosuppressive therapy in as many as half the patients. Our forthcoming study aims to (i) describe homogeneously-studied and prospectively-analysed cohort of childhood ES, (ii) separate ES from specific immune deficiency (especially fas gene mutations), generalised autoimmune/inflammatory disorders and genetic diseases, (iii) identify well-defined ES subsets, (iv) establish prognostic factors and optimal treatment within these subsets.

Carboplatin-epirubicin regimen for the treatment of hepatoblastoma.

BACKGROUND: In order to lower the long-term toxicity of chemotherapy for hepatoblastoma patients, a prospective study was designed based on pre-operative chemotherapy combining carboplatin and epirubicin (CE). PROCEDURES: Patients under 16 years of age with an epithelial hepatic tumor diagnosed by ultrasound or CT scan and a high serum alpha-foetoprotein (AFP) level were eligible. Patients were treated with a pre-operative chemotherapy regimen combining carboplatin 600 mg/m(2) and epirubicin 80 mg/m(2). Tumor resectability was assessed after four courses given at 3-week intervals. After surgery, patients were given two more courses of CE. Response was assessed based on a drop in serum AFP and tumor shrinkage. RESULTS: Between July 1988 and August 1995, 27 patients with a hepatoblastoma were included. The initial PRETEXT group according to the SIOPEL classification was: group 2 (5 pts), group 3 (15 pts), group 4 (5 pts), and 2 pts were not assessed. Six patients had lung metastases. Response was partial response (PR) in 20/27 (74%) patients, disease was stable in 3 and 4 had progressive disease (PD). A complete surgical resection was performed in 21 pts. Five-year overall and disease-free survival (DFS) were respectively 56% (95%CI: 37-72%) and 63% (95%CI: 44-78%). During the same time period, 7 pts with a hepatocellular carcinoma were treated according to this protocol. Only one achieved a PR. Toxicity was mostly hematologic with > or =grade 3 leukopenia in 23% of the courses, > or =grade 3 thrombocytopenia in 29% of the courses and anemia in 22%. CONCLUSION: The CE protocol is feasible and efficient in hepatoblastoma. However, only a randomized study will permit a valid comparison of the efficacy of cisplatin and carboplatin for the treatment of these patients.

[3-dimensional reconstruction technic using power Doppler. In vitro use on normal and stenosed pulmonary artery bifurcations]. / Technique de reconstruction tridimensionnelle en doppler puissance. Application in vitro sur une bifurcation artérielle pulmonaire normale et sténosée.

Power Doppler imaging is an ultrasonic technique representing circulating red cells as a colour signal independent of their direction and angle of analysis. This noninvasive technique provides a morphological representation of blood flow within a blood vessel. This in vitro study in pulsed flow enabled three-dimensional reconstruction of blood flow in the bifurcation of the pulmonary artery with automatic shifting of the ultrasound probe and an integral digital transfer of the echographic data. The software for treating the images and for volumic reconstruction of the flow is explained. This technique provides a quantitative method of assessing residual intrastenotic flow with a simple computer system.

Use of transcriptional regulatory elements of the MUC1 and ERBB2 genes to drive tumour-selective expression of a prodrug activating enzyme.

In order to exploit differences in gene expression between normal and malignant cells for genetic prodrug-activation therapy, we have generated recombinant retroviruses containing the herpes simplex virus thymidine kinase coding region cloned downstream of sequences derived from the 5'-flanking regions of the MUC1 and ERBB2 genes. Transduction with retroviruses containing MUC1 promoters resulted in an increase in GCV sensitivity in MUC1 positive cells. A further increase in GCV sensitivity was achieved when MUC1-positive cells were transduced with retroviruses containing chimeric-MUC1/ERBB2 promoters. No significant sensitization to GCV was observed when MUC1-negative cells were transduced with these recombinant retroviruses. These results suggest that one may be able to develop a tumour-selective therapy by utilizing the transcriptional regulatory regions of the MUC1 and ERBB2 genes to drive the expression of suicide genes.

Diabetic-like retinopathy ameliorated with the aldose reductase inhibitor WAY-121,509.

PURPOSE: To evaluate the efficacy of WAY-121,509, a potent new aldose reductase inhibitor (ARI), in preventing the retinopathy that develops in the galactose-fed rat model of diabetic ocular complications. METHODS: Sprague-Dawley rats were randomized into treatment and duration groups and fed diets with either 50% starch of 50% galactose with or without WAY-121,509 (25 mg/kg body weight per day). Progression of cataracts was monitored by slit-lamp biomicroscopy. After duration of 4, 8, 16, and 24 months, levels of plasma glucose and glycated hemoglobin, as well as erythrocyte and retinal galactose and galactitol, were measured in rats in each group. Retinal vasculatures of the 24-month rats were isolated by elastase digestion and analyzed by computer-assisted morphometry. RESULTS: Mature, diabetic-like cataracts developed within 5 weeks in all the galactose-fed, untreated rats, but only nonprogressive anterior cortical opacities were present in lenses of 85% of the ARI-treated galactosemic animals after 3 months. Plasma glucose remained the same in all groups. Erythrocyte and retinal galactose and glycated (galactosylated) hemoglobin were elevated with galactosemia and were unaffected by ARI treatment. Erythrocyte and retinal galactitol levels were decreased by 91% and 95%, respectively, with inhibitor treatment. At 24 months, capillary length, width, density, the number of microaneurysms, and the percent of capillary length involved in intraretinal microvascular abnormalities, expressed as hypercellular channels with diameters > 20 microns, were significantly increased by galactosemia and were attenuated in the galactose-fed, ARI-treated group. CONCLUSIONS: A dose of WAY-121,509 sufficient to reduce retinal polyol levels by 95% ameliorated the development of galactose-induced cataracts and diabetic-like retinopathy but was insufficient to prevent early lens opacifications or all the diabetic-like retinal microangiopathies.

Le diagnostic antenatal de la drepanocytose

Les auteurs rapportent leur experience du diagnostic antenatal de la drepanocytose. Ce travail a ete justifie par l'incidence de cette maladie. 25 (12 pour cent) de toute drepanocytose; 1;6 pour cent d'incidence neonatale; pres de 2500 grossesses a risque de drepanocytose. Ces chiffres ont commande des campagnes d'information assurees par tous les mass -media. Cette information si elle a amene a une meilleure surveillance des drepanocytaires existants; n'en a pas moins engendre une engoisse insupportable au sein des couples d'heterozygotes et a plus forte raison au sein de la famille ayant deja vecu l'experience de la maladie. La recession economique n'autorisant plus l'evacuation sanitaire; les auteurs ont entrepris par une attitude orignale; de mettre a la portee de la plupart des bourses; le diagnostic antenatal de la maladie. Une collaboration scientifique s'est ainsi etablie entre Bordeaux et Libreville. L'experience porte sur 21 PVC dont 16 dossiers ont ete suivis jusqu'au terme de la grossesse

Definition of the human renal cell carcinoma phenotype using monoclonal and polyclonal antibodies: a tumor marker study.

Previous studies have demonstrated a high level of heterogeneity associated with human renal cell carcinoma (RCC). In order to probe further this heterogeneity monoclonal antibodies were produced after immunization of mice with extracts of fresh renal tumor specimens. Four monoclonal antibodies designated LD-M1, LD-M2, LD-M5, and LD-M8 were generated and characterized immunohistochemically on a panel of tissue sections. The LD monoclonal antibodies strongly stained paraffin sections obtained from 77 to 100% of cases of RCC. Testing the sections with a library of polyclonal and monoclonal antibodies resulted in the definition of the following immunohistochemical phenotype of RCC: positive with the LD-M1, LD-M2, Ld-M5, LD-M8, Uro-2, Uro-7, Uro-10, cytokeratin, keratin, TPA, vimentin, Fx1A, retinol binding protein, CALLA and B72 antibodies; negative with the prekeratin, desmin, A5.48, uromucoid, and CEA antibodies. The pattern of immunohistochemical activity indicates that some RCC tumor cells contain epitopes associated with distal tubules in addition to previously documented antigens present in proximal tubules. Using a solid-phase competition radioimmunoassay it was observed that the serum of patients with renal cell carcinoma contains a circulating LD-M5-reactive tumor-associated antigen.