Anne Lambilliotte

Nitrous oxide sedation in pediatric patients undergoing gastrointestinal endoscopy.

BACKGROUND The ideal medication to administer to children before gastrointestinal endoscopy procedures has yet to be found. The efficacy of using inhaled nitrous oxide during endoscopy in children was assessed in a pilot study. METHODS Patients aged 5 to 17 years, referred to our hospital for diagnostic upper gastrointestinal endoscopy or rectosigmoidoscopy procedures, were eligible for enrollment in this study. All received 50% nitrous oxide in oxygen (Entonox; AGA, Rueil-Malmaison, France) before endoscopy and some of them again during endoscopy. The pediatric endoscopist and the nurse performing the procedure were separately asked to rate cooperation, emotional state, drowsiness and overall efficacy of sedation. Oxygen saturation and adverse effects were recorded throughout the procedure. After endoscopy, children scored their degree of pain during the procedures on a visual analog scale (0, no pain; 100, agony) and on a body outline (projective method). Any adverse effects were noted. RESULTS Thirty-seven patients were enrolled in the study. Thirty patients underwent diagnostic upper gastrointestinal endoscopy and seven diagnostic rectosigmoidoscopy. The median time from administration of nitrous oxide until insertion of the endoscope was 5 minutes (range, 3-8 minutes). Good or excellent efficacy of the sedation was noted in 92% of children by the endoscopist and in 89% by the nurses. Good or excellent cooperation was noted in 92% of the children by the endoscopist and in 78% by the nurses. The childrens pain score on the visual analog scale ranged from 5 to 100 (median, 20) for upper gastrointestinal endoscopy and from 0 to 30 (median, 0) for rectosigmoidoscopy. The time of discharge after endoscopy, defined as the time elapsed between the end of the endoscopy and discharge from the endoscopy suite, varied from 1 to 7 minutes (median, 1.5 minutes). CONCLUSION Entonox provides rapid and effective analgesia without heavy sedation, leads to adequate relaxation and cooperation, and facilitates quick and efficient endoscopy. The effect of Entonox was of short duration, allowing the children to leave the endoscopy unit without need for a long recovery period. The adverse effects of Entonox appeared to be minor, and their duration was always brief. Nitrous oxide-oxygen inhalation may provide a valuable alternative to conventional sedation regimens during gastrointestinal endoscopy in children, but randomized and prospective studies comparing nitrous oxide sedation and conventional sedation regimens are necessary.

Classification of and risk factors for hematologic complications in a French national cohort of 102 patients with Shwachman-Diamond syndrome

Background Patients with the Shwachman-Diamond syndrome often develop hematologic complications. No risk factors for these complications have so far been identified. The aim of this study was to classify the hematologic complications occurring in patients with Shwachman-Diamond syndrome and to investigate the risk factors for these complications. Design and Methods One hundred and two patients with Shwachman-Diamond syndrome, with a median follow-up of 11.6 years, were studied. Major hematologic complications were considered in the case of definitive severe cytopenia (i.e. anemia <7 g/dL or thrombocytopenia <20×109/L), classified as malignant (myelodysplasia/leukemia) according to the 2008 World Health Organization classification or as non-malignant. Results Severe cytopenia was observed in 21 patients and classified as malignant severe cytopenia (n=9), non-malignant severe cytopenia (n=9) and malignant severe cytopenia preceded by non-malignant severe cytopenia (n=3). The 20-year cumulative risk of severe cytopenia was 24.3% (95% confidence interval: 15.3%–38.5%). Young age at first symptoms (<3 months) and low hematologic parameters both at diagnosis of the disease and during the follow-up were associated with severe hematologic complications (P<0.001). Fifteen novel SBDS mutations were identified. Genotype analysis showed no discernible prognostic value. Conclusions Patients with Shwachman-Diamond syndrome with very early symptoms or cytopenia at diagnosis (even mild anemia or thrombocytopenia) should be considered at a high risk of severe hematologic complications, malignant or non-malignant. Transient severe cytopenia or an indolent cytogenetic clone had no deleterious value.

Treatment outcome after low intensity chemotherapy [CVP] in children and adolescents with early stage nodular lymphocyte predominant Hodgkin's lymphoma - an Anglo-French collaborative report.

PURPOSE To examine whether three cycles of a low-intensity chemotherapy consisting of cyclophosphamide [500 mg/m(2) - day 1], vinblastine [6 mg/m(2) - days 1 and 8] and prednisolone [40 mg/m(2) - days 1-7] (CVP) is safe and therapeutically effective in children and adolescents with early stage nodular lymphocyte predominant Hodgkin lymphoma [nLPHL]. PATIENTS AND METHODS Fifty-five children and adolescents with early stage nLPHL [median age 13 years, range 4-17 years] diagnosed between June 2005 and October 2010 in the UK and France are the subjects of this report. Staging investigations included conventional cross sectional as well as 18 fluro-deoxyglucose [FDG] PET imaging. Histology was confirmed as nLPHL by an expert pathology panel. RESULTS Of the 45 patients, who received CVP as first line treatment, 36 [80%, 95% Confidence Interval [CI]: (68; 92)] either achieved a complete remission [CR] or CR unconfirmed [CRu], the remaining nine patients achieved a partial response. All nine subsequently achieved CR with salvage chemotherapy [n=7] or radiotherapy [n=2]. Ten patients received CVP at relapse after primary treatment that consisted of surgery alone and all achieved CR. To date, only three patients have relapsed after CVP chemotherapy and all had received CVP as first line treatment at initial diagnosis. The 40-month freedom from treatment failure and overall survival for the entire cohort were 75.4% (SE ± 6%) and 100%, respectively. No significant early toxicity was observed. CONCLUSIONS Our results show that CVP is an effective chemotherapy regimen in children and adolescents with early stage nLPHL that is well tolerated with minimal acute toxicity.

Gastrostomy as a decompression technique in children with chronic gastrointestinal obstruction.

Background Percutaneous or surgical insertion of gastrostomy tubes for feeding children has been well described. However, there is no report of percutaneous gastrostomy for chronic decompression in children with chronic gastrointestinal obstruction. The objective of this study was to evaluate this technique. Methods Eighteen gastrostomies were performed for gastrointestinal decompression in children. The patients ranged in age from 2 to 125 months (median: 15.5), and all had prolonged hospital stays for severe disease: severe gastroparesis and/or duodenal dysmotility (n = 8), duodenal stenosis (n = 2), chronic intestinal pseudo-obstruction (n = 4), enterocolitis (n = 2), and metastatic abdominal carcinomatosis (n = 2). The duration of symptoms before gastrostomy placement ranged from 0.5 to 44 months (median: 2), with major symptoms including epigastric pain, early satiety, nausea, vomiting, and bloating. Results The goals of gastric decompression and removal of the nasogastric tube were achieved in all patients, and all had significant relief of both nausea and emesis. Oral intake of liquids and soft foods was possible in 17 of 18 of the children. The tubes were kept in place for a median of 22.5 months (range, 2–73). There was neither long-term morbidity nor mortality associated with the presence of the tube. Seventeen patients returned home with gastric decompression and cyclic parenteral nutrition, two of them for terminal care. Six patients died. In all patients, gastrostomy was used throughout and did not contribute to the death of the patients. For seven children, tubes were removed because of resolution of small bowel or gastric outlet obstruction. Conclusions Gastrostomy is an efficient and well-tolerated method of achieving long-term gastric decompression in children with abdominal obstruction not amenable to surgery and/or resistant to medical treatment.

Outcome of children and adolescents with recurrent/refractory classical Hodgkin lymphoma, a study from the Société Française de Lutte contre le Cancer des Enfants et des Adolescents (SFCE)

There is little data available regarding children and adolescents with Hodgkin lymphoma (HL) who relapse after combined‐modality treatment, even though they have a substantial chance of cure. The purpose of this national retrospective study was to evaluate the outcome of patients with recurrent/refractory HL and determine adverse prognostic factors. From 1990 to 2006, 70 patients (median age 13·9 years) with refractory (n = 31) or first relapse (n = 39) HL were identified. Median time from end of treatment to relapse was 6 months (3–56). Relapses occurred in irradiated areas in 43/70 patients. Salvage therapy consisted of chemotherapy and 50 patients received high‐dose chemotherapy with autologous stem cell transplantation. Radiotherapy was performed in 29 cases, tandem autologous transplantation in five and allograft in three. With a median follow‐up of 40 months (2–140), significant prognostic factors were time to progression/relapse and response to therapy before autograft. Event‐free survival and overall survival in patients with refractory disease, early relapse and late relapse were 35 ± 9%, 67 ± 11%, 76 ± 10% and 48 ± 11%, 89 ± 7% and 80 ± 10%, respectively. As progression <3 months was a major adverse prognostic factor, novel therapeutic approaches are needed for this group of patients. By contrast, patients have substantial chance of long term second remission in case of relapse >3 months.

Langerhans cell histiocytosis: therapeutic strategy and outcome in a 30‐year nationwide cohort of 1478 patients under 18 years of age

The French national cohort of children with Langerhans cell histiocytosis (LCH) has included 1478 patients since it was established in 1983. LCH therapeutic strategies substantially changed in 1998, so we have divided the cohort into two 15‐year periods. Starting in 1998, therapy duration increased from 6 to 12 months, repeated induction therapy was performed in cases showing a poor response to the first induction with vinblastine and steroids, and refractory disease in a risk organ (RO+) was treated with cladribine and cytarabine. A total of 483 (33%) patients were enrolled before 1998, and 995 (67%) after 1998. Five‐year survival was 96·6% (95% confidence interval: 95·4–97·5%) overall, improving from 92% pre‐1998 to 99% post‐1998 (P < 0·001 adjusted to disease extent). This change was supported by an increase in 5‐year survival from 60% to 92% in the RO+ group. Survival was particularly associated with cladribine and cytarabine among refractory RO+ patients. Disease reactivation was slightly less frequent after 1998, due to better enrolment of single‐system patients, extended therapy duration, and more efficient second‐line therapy. The crude rates of endocrine and neurological sequelae (the most frequent sequelae) appeared to improve over time, but this difference was not observed when the analysis was stratified by disease extent.

Thymus and mediastinal node involvement in childhood langerhans cell histiocytosis: Long-term follow-up from the French national cohort

Mediastinal involvement (MI) in Langerhans cell histiocytosis (LCH) has been rarely reported. Here, we describe the clinical, radiological, and biological presentation, and the outcome of childhood LCH with MI.

Continuous infusion of ceftazidime in the empiric treatment of febrile neutropenic children with cancer.

Purpose Infection remains one of the most important complications in cancer therapy. The choice of antibiotics and the method of administration can affect results. Beta-lactam antibiotics can be administered by several short injections per day or by continuous infusion. The latter modality may provide superior pharmacokinetics. Patients and Methods The authors studied the pharmacokinetics of ceftazidime in children treated for malignancy and in febrile aplasia after chemotherapy. They received a continuous infusion of ceftazidime (200 mg/kg/day) after a loading dose (65 mg/kg/day) administered with amikacin (25 mg/kg/day) and vancomycin (50 mg/kg/day). Results Twenty-three pharmacokinetic studies were performed. Mean ceftazidime serum levels were 31.1 ± 11.9, 31.2 ± 10, 32.4 ± 11.6, 33 ± 11.6, and 30.4 ± 12.1 mg/L at 25, 27, 30, 36, and 43 hours, respectively. Treatment was tolerated well. There were no toxic or infectious deaths. Conclusions Ceftazidimes time-dependent pharmacokinetics shows the advantage of continuous infusion. This study confirmed the feasibility and safety of this administration schedule in the empiric treatment of febrile neutropenic children with cancer.

Anomalies dentaires après chimiothérapie anticancéreuse

: Chemotherapy administered during childhood may induce dental abnormalities, such as acquired amelogenesis imperfecta, microdontia, hypodontia and altered root morphology. The magnitude of the defect varies according to the cytotoxic agents, the duration of their use and the stage of tooth development at the time of chemotherapy. Patients who received high-dose chemotherapy before the age of 5 are particularly concerned. The dental supervision of these children is based upon three orthopantomograms: the first one has to be performed before starting chemotherapy and will be used as a reference; the second is done soon after the drug therapy in order to evaluate the first consequences; the third is performed after the eruption of all permanent teeth (age 12-13 in average) in order to determine the dental abnormalities. In case of hypodontia, orthodontic treatment must be considered, but it is necessary to take into account the fact that it may increase the risk of root resorption. Preventive dental care is important for these children. It involves meticulous oral hygiene and frequent dental visits to assess and maintain dental health.

Revisiting Splenectomy in Childhood Immune Thrombocytopenic Purpura in the Era of New Therapies: The French Experience

Objective: While splenectomy is the gold standard treatment for refractory primary immune thrombocytopenia (ITP) in adult, its place remains debated in children. The French Rare Disease Plan provided us the opportunity to conduct a collaborative study of the efficiency and tolerance of this procedure in childhood ITP. Patients and methods: A retrospective study was conducted in France in order to identify children with ITP treated with splenectomy during a 9-year period. A total of 78 children were included. Data from the ongoing CEREVANCE national cohort of childhood auto-immune cytopenia in 30 units were reviewed and completed by a direct contact with the referent physicians. International terminology for response definition was used. Relapsefree survival was assessed by the Kaplan-Meier method. Results: The median ages at ITP diagnosis and splenectomy were 9.6 and 12.4 years respectively. The median duration of ITP before splenectomy was 24 months (1-162); 62 children had chronic ITP. The median number of treatment lines before splenectomy was 2 (1-7). Laparoscopy was used in 81% of cases. Four children underwent immediate surgical complications. With a median follow-up of 41 months, complete remission (CR) was maintained at the latest news in 84% of children. CR was obtained in 77% of cases with intra-splenic platelets destruction, and in no case with non-splenic destruction (p=0.11). Using a very strict definition for relapse, the 5-year relapse-free survival was 51% [IC95% 37-64]. No death or overwhelming sepsis was reported. Conclusions: In this national study with a long term follow up, the excellent benefit/risk ratio of splenectomy for refractory ITP confirms that in skilled and concerted teams, the procedure is still at the forefront of curative treatments. Isotopic evaluation is of value but other prognostic factors for CR are to be determined. Lifelong survey of potential infectious and thrombotic risk at adult age has to be coordinated by the referring physician. The place for other therapeutic options, in order to postpone as late as possible the splenectomy in childhood ITP is now to be determined.