[Ovarian teratoma in children. Clinical case and review of the literature]. / Tératome ovarien chez l'enfant. Revue de la littérature à propos d'un cas clinique.

Summmary : Teratomas are the most common histologic type of germ cell tumors in pediatrics. There are two types of teratomas, mature, benign and immature, malignant. Initial diagnosis is essential for optimal management. This work, based on a clinical case, aims to review the clinical, radiological, biological and histological characteristics allowing them to be differentiated.

Les tératomes sont le type histologique le plus fréquent des tumeurs germinales en pédiatrie. Il existe deux types de tératomes, matures, bénins et immatures, malins. Le diagnostic initial est primordial pour une prise en charge optimale. Ce travail, basé sur un cas clinique, a pour but de reprendre les caractéristiques cliniques, radiologiques, biologiques et histologiques permettant de les différencier.

[How I explore hémostatic abnormalities in pediatrics]. / Comment j'explore. Une anomalie du bilan d'hémostase en pédiatrie.

Hemostasis work-up is frequently requested in pediatric cares and can often seem complicated to interpret when certain results return to be abnormal. In addition, these biological tests are very sensitive and several pre-analytical conditions can influence them and skew the results, leading to erroneous analyzes and diagnoses. Indeed, systemic inflammation, anemia or even only the delay between blood sampling and analysis can make the results more difficult to be interpreted. However, when the tests have been carried out under good conditions, having in mind a few basic knowledge of hemostasis can easily help to first distinguish a pathology of primary hemostasis from a coagulopathy. Secondly, depending on the abnormal biological tests, complementary oriented assays may then be requested, ideally in a laboratory specialized in hemostasis, in order to confirm or rule out a true hemorrhagic pathology.

Le bilan d'hémostase standard, fréquemment demandé en pédiatrie, peut souvent sembler compliqué à interpréter lorsque certains résultats reviennent anormaux. De plus, l'influence des conditions pré-analytiques, parfois méconnues, sur ces tests biologiques extrêmement sensibles peut en fausser les résultats et entraîner des analyses et des diagnostics erronés. En effet, des paramètres tels que l'inflammation, un contexte d'anémie ou encore un délai trop important entre le prélèvement sanguin et l'analyse peuvent rendre les résultats ininterprétables. Lorsque les tests ont été réalisés dans de bonnes conditions, quelques bases de physiologie de l'hémostase ainsi que quelques spécificités liées à la pédiatrie permettent facilement de s'orienter vers une pathologie de l'hémostase primaire ou de la coagulation. Dans un second temps, en fonction des tests biologiques altérés, des dosages complémentaires orientés peuvent être demandés, idéalement dans un laboratoire spécialisé en hémostase, afin d'affirmer ou infirmer une véritable pathologie hémorragique.

[The rise of targeted therapies in pediatric oncology]. / L'essor des thérapies ciblées en oncologie pédiatrique.

Cancers are rare pathologies in children. Improvement in survival rates has been obtained thanks to new therapeutic strategies based on the identification of risk factors. Targeted therapies in paediatric oncology are new treatments providing hope that cure is achievable without long-term sequelae.

Les cancers pédiatriques sont des pathologies rares. L'amélioration du taux de survie a été obtenue par de nouvelles stratégies de traitement basées sur l'identification de facteurs de risque. Les thérapies ciblées en oncologie pédiatrique, nouvelle arme thérapeutique, sont porteuses d'espoir de guérison, sans séquelles à long terme.

[What follow-up after pediatric cancer ? The SALTO consultation experience]. / Quel suivi après un cancer pédiatrique ? L'expérience de la consultation SALTO.

During the past 50 years, the mortality due to childhood cancers decreased dramatically thanks to improvements in supportive care and the use of multimodal approaches. In this context, the long-term follow up after childhood cancer has become a main concern for pediatric oncologists. The SALTO programme was developed in 2012 at the CHR Citadelle in Liège in order to organize a multidisciplinary long-term follow-up for the patients previously treated in our department for a childhood cancer. The aim of the present study was to review, for the most frequent childhood cancers, the long-term sequellae and the second cancers developed by the patients participating to the SALTO programme in order to define the follow-up needed. Our data confirm the importance of a multidisciplinary long-term follow-up, based on the treatments received and following international guidelines.

Au cours des cinquante dernières années, la mortalité liée aux cancers pédiatriques a fortement diminué grâce à une amélioration des soins de support et à l'utilisation d'approches multimodales. Dans ce contexte, le devenir à long terme des patients guéris d'un cancer pédiatrique est devenu une des préoccupations majeures pour les oncologues pédiatres. Dans cette optique, la consultation SALTO («Suivi À Long Terme en Oncologie¼) a été mise en place en 2012 au CHR de la Citadelle pour assurer le suivi multidisciplinaire des adultes ayant été traités dans notre secteur d'hémato-oncologie pédiatrique. L'objectif de cette étude a été de revoir, pour les cancers pédiatriques les plus fréquents, les séquelles et les tumeurs secondaires présentées par les patients suivis en consultation SALTO afin de préciser les modalités du suivi au long cours après cancer pédiatrique. Nos résultats confirment l'importance d'un suivi multidisciplinaire à long terme adapté aux traitements reçus, sur base de recommandations internationales.

[Pediatric cutaneous mastocytosis]. / Cas clinique : La mastocytose cutanée pédiatrique.

Mastocytosis are orphan diseases characterized by the accumulation of mast cells in one or more organs. A distinction is made between systemic forms (10 %) and pure cutaneous forms (90 %), the latter being mainly pediatric and generally having a spontaneously favourable prognosis. In the absence of a systemic sign, the diagnostic criteria for cutaneous mastocytosis are Darier's sign, in principle, pathognomonic, as well as skin histology confirming mast cell infiltration. The treatment is essentially preventive (avoidance of factors triggering degranulation) and symptomatic (antihistamine agents).

Les mastocytoses sont des maladies orphelines caractérisées par l'accumulation de mastocytes dans un ou plusieurs organes. On distingue les formes systémiques (10 %) des formes cutanées pures (90 %). Ces dernières sont principalement pédiatriques et ont, généralement, un pronostic spontanément favorable. En cas d'absence de signe d'appel systémique, les critères de diagnostic de mastocytose cutanée sont le signe de Darier, en principe, pathognomonique ainsi que l'histologie cutanée affirmant l'infiltration mastocytaire. Le traitement est essentiellement préventif (éviction des facteurs déclenchant la dégranulation) et symptomatique (médicaments antihistaminiques).

[Multidisciplinary management of the pediatric sickle cell patient in 2019]. / Prise en charge multidisciplinaire du patient drépanocytaire pédiatrique en 2019.

Sickle cell disease is a common genetic disorder that affects haemoglobin. It is manifested by haemolytic anaemia and vaso-occlusive crisis. It can affect all organs and its evolution is unpredictable. The multidisciplinary management of pediatric patients who suffer from it is essential to adapt their treatment and optimize their evolution. One of the major challenges is to succeed the transition to adult medicine. New therapeutic perspectives are in development and look promising.

La drépanocytose est une maladie génétique fréquente qui affecte l'hémoglobine. Elle se manifeste par une anémie hémolytique et des phénomènes vaso-occlusifs. Elle peut toucher tous les organes et son évolution est imprévisible. La prise en charge multidisciplinaire des patients pédiatriques qui en souffrent est essentielle pour optimaliser leur évolution et adapter leur traitement. Un des défis majeurs est de réussir la transition vers la médecine adulte. De nouvelles perspectives thérapeutiques sont en développement.

[Epidemiology of childhood cancer, a single-center study (1985-2016)]. / Epidémiologie des cancers de l'enfant, une étude monocentrique (1985-2016).

Cancer is the second leading cause of death among children aged 5 to 14, after accidents. We conducted a study on the epidemiology of childhood cancer in the university pediatric oncology department of the CHU-CHR in Liège, Belgium. We studied a cohort of 662 patients between the ages of 0 and 17 whose malignancy diagnosis was made between 1985 and 2016. The analyzes were performed retrospectively using medical files. The number of new cases, the proportion of different cancers, sex ratio, age at diagnosis and survival at 5 and 10 years were the epidemiological factors studied.We have been able to show an increase in the number of new diagnoses per year. More than 40 % of childhood cancers occur before the age of five. The most common neoplasias are leukemias, tumors of the central nervous system and lymphomas. This distribution is influenced by age. All malignant tumours combined, we observed a slightly larger proportion of affected boys than girls. Overall survival at 5 years reaches 80.2 %. However, it varies according to the type of tumour from 59.3 % for malignant soft tissue tumors up to 100 % for hepatoblastomas.

Le cancer est la deuxième cause de décès chez les enfants de 5 à 14 ans, après les accidents. Nous avons réalisé une étude sur l'épidémiologie des cancers de l'enfant au sein du service universitaire d'oncologie pédiatrique du CHU-CHR de Liège. Nous avons étudié une cohorte de 662 patients, âgés de 0 à 17 ans, dont le diagnostic de tumeur maligne a été posé entre 1985 et 2016. Le nombre de nouveaux cas, la proportion des différents cancers, le sex ratio, l'âge au diagnostic et la survie à 5 et 10 ans ont été les facteurs épidémiologiques étudiés. Nous avons pu démontrer une augmentation du nombre de nouveaux diagnostics par an. Plus de 40 % des cancers de l'enfant surviennent avant l'âge de 5 ans. Les néoplasies les plus fréquentes sont les leucémies, les tumeurs du système nerveux central et les lymphomes. Cette répartition est néanmoins influencée par l'âge. Toutes tumeurs malignes confondues, nous avons observé une proportion légèrement plus grande de garçons atteints que de filles. La survie globale à 5 ans s'élève à 80,2 %. Elle varie cependant selon le type de tumeur de 59,3 % pour les tumeurs malignes des tissus mous jusqu'à 100 % pour les hépatoblastomes.

[Cardiac complications of sickle cell disease in children]. / Complications cardiaques de la drépanocytose chez l'enfant.

Sickle cell disease (SCD) is a genetic disorder due to an abnormal gene coding for the chain ? of the hemoglobin. The main clinical manifestations related to the major forms of SCD (SS-, SC-, and S-thalassemia) are chronic hemolysis, susceptibility to infections and vasoconstrictive crisis causing micro-emboli and/or infarction responsible for acute or chronic organ lesions. The latest are enhanced by tissue iron overload due to repeated blood transfusions. Cardiac complications are an important part of morbidity and mortality of SCD. They are due to chronic anemia, vaso-occlusive crisis, iron overload, pulmonary, renal and hepatic damage. In children, cardiac complications of SCD are not sufficiently identified. They principally consist in dilated or restrictive cardiomyopathy and pulmonary arterial hypertension. Sudden death and acute cardiac failure due to myocardial infarction or arrhythmias have become exceptional. This review focuses on the pathophysiological aspects of cardiac complications of SCD and on the diagnostic tools allowing their early recognition and improvement of patient care.

La drépanocytose ou Sickle Cell Disease (SCD) est une maladie génétique qui résulte d'une anomalie du gène codant pour la chaîne ? de l'hémoglobine. Les syndromes drépanocytaires majeurs (formes SS, SC et S?-thalassémie) se traduisent par une hémolyse chronique, une susceptibilité aux infections et des crises vasoocclusives. Celles-ci entraînent des micro-embolies ou infarctus responsables des lésions organiques aiguës et chroniques. Les transfusions sanguines répétées ont pour conséquence une surcharge en fer, également impliquée dans les atteintes multi-organiques. Les complications cardiaques conditionnent la morbidité et la mortalité des sujets drépanocytaires. Elles sont dues aux conséquences de l'anémie chronique, des crises vaso-occlusives, de la surcharge martiale et des répercussions des atteintes pulmonaires, rénales et hépatiques. Les complications cardiaques , essentiellement les cardiomyopathies dilatées ou restrictives et l'hypertension artérielle pulmonaire, sont souvent méconnues chez l'enfant. Les cas de mort subite ou d'insuffisance cardiaque aiguë sur infarctus du myocarde ou arythmie sont devenus exceptionnels. Cette revue de la littérature aborde les aspects physiopathologiques des complications cardiaques de la drépanocytose, les techniques de dépistage et leurs implications dans la prise en charge des patients.

[How I explore and treat a neonatal renal vein thrombosis: a case report]. / Comment j'explore et traite une thrombose veineuse renale néonatale: àpropos d'un cas.

Neonatal renal vein thrombosis is a rare condition. The present case is rather unfrequent and particularly educative since it shows the complete diagnostic triad including hematuria, flank mass and thrombocytopenia. The diagnosis relies on the demonstration, by Doppler ultrasound, of an obstructed renal venous bed. The investigation is completed by a platelet count and the determination of the prothrombin time, of the activated partial thromboplastin time as well as of the concentration of fibrinogen. The screening also includes the search for a possible etiology, such as a deficiency in coagulation proteins, the presence of antiphospholipid antibodies or of a genetic mutation of one of the coagulation factors. Since there exist no evidence based guidelines for the management of the disease, we will discuss the diagnosis and treatment in relation with the published literature.

Paravertebral Burkitt's Lymphoma in a Child: An Unusual Presentation.

Paravertebral malignant tumors constitute 4.8% of cancer cases in pediatric oncology and are mostly composed of neuroblastoma (46.4%) and soft tissue sarcomas (35.7%). We describe the case of a Caucasian 6-year-old boy who was admitted for middle back pain radiated to limbs and progressively increasing weakness of the legs, suggesting a spinal cord disease. The exploration revealed two paravertebral masses extending through the neural foraminae into the epidural space. The association with elevated serum neuron specific enolase suggested at first the diagnosis of neuroblastoma, but the pathological examination revealed a Burkitt's lymphoma. This is a rare location of sporadic Burkitt's lymphoma with neurologic syndrome as first symptoms.

Sickle cell disease from Africa to Belgium, from neonatal screening to clinical management.

AIM: To describe the severity of sickle cell disease (SCD) in newborns in Belgium and evaluate the impact of neonatal screening (NS) on clinical outcome. METHODS: Universal NS of umbilical cord blood for hemoglobinopathy was progressively deployed in Brussels and Liège starting in 1994. No particular population was targeted. Samples were analyzed initially using the isoelectric focusing technique and since 2008 the capillary electrophoresis technique. If a hemoglobin variant was suspected, further analysis was carried out using high performance liquid chromatography. Children presenting major hemoglobinopathy, especially SCD, were referred to a specialized centre for comprehensive management. Preventive measures included antipneumococcal prophylaxis immunization/antibiotic therapy, parental training to recognize severe anemia and splenic sequestration, and transcranial ultrasound recording for early detection of intracranial stenosis. A database was set up in Belgium to collect clinical and laboratory data including parental phenotype, diagnostic technique (neonatal screening or not), major clinical events (episodes of dactylitis, acute chest syndrome, severe anemia, infection, etc), number and duration of required hospitalizations, and treatment used. RESULTS: Screening of 222352 newborns in maternity units in Brussels led to diagnosis of SCD in 145 patients, Adequate data for analysis of clinical outcome was available for 96 of these children born before 2007. Median age in the study group was 4.2 years and the total duration of follow-up was 510 years. Most cases occurred in families from the Democratic Republic of Congo. (64/96 patients; 66.7%) and involved homozygous hemoglobin S disease (80/96 patients; 83.3%). Twenty-seven percent of patients (26/96) presented no severe clinical events during the study (17 SS, median age 2,1 years (0-13.1 years). Conversely 33% presented an episode of dactylitis and 47.9% (46/96) presented recurrent vasoocclusive crises. Severe anemia was observed in 39.6% (38/96) of cases. Six patients (6.3%) developed septicemia despite prophylactic antibiotic therapy and anti-pneumococcal immunization using heptavalent conjugate vaccine and polysaccharide vaccine, No penicillin-resistant strains were observed. The incidence of stroke was 2.1% (3/96). Two patients presenting homozygous hemoglobin S disease died due to septicemia due to non-compliance with antibiotic therapy in one case and severe anemia in one case. All episodes of septicemia and both deaths occurred at the beginning of the NS program. Hydroxyurea therapy was used in 30 patients (31.2%) including 7 in whom transcranial Doppler depicted blood flow abnormalities and 8 in whom allogeneic bone marrow transplantation was performed. CONCLUSIONS: Sickle cell disease is still associated with high morbidity and mortality but clinical care has improved and no death has occurred in the last 10 years. NS is an effective tool for early detection and management of SCD. Neonates with SCD diagnosed by NS in Belgium presented severe manifestations, but clinical outcomes were improved by comprehensive management.

[Renal tumors in children. A single center study of 31 cases]. / Les tumeurs rénales de l'enfant. Une etude monocentrique: a propos de 31 cas.

In order to illustrate epidemiologic features and survival rate, 31 Wilm's tumours treated in our institution have been retrospectively studied. The mean age at diagnosis in our series was surprisingly higher than usually described: 25% of the patients were older than 8 years. Moreover, a mesoblastic nephroma congenital kidney tumour--appeared in a 10 month old girl. Symptoms were usually abdominal mass or gross hematuria. Young children are often brought to medical attention because of abdominal swelling: a large flank mass was palpable in all children under 5 years. Our study shows that preoperative chemotherapy results in a less intensive treatment regimen conducting probably to less sequellae. Event free survival and overall survival were respectively 87% and 94% at 10 years after diagnosis. Renal insufficiency was the most important side effect: 2 children required renal transplantation.

Neonatal haemoglobinopathy screening in Belgium.

BACKGROUND: A neonatal haemoglobinopathy screening programme was implemented in Brussels more than a decade ago and in Liège 5 years ago; the programme was adapted to the local situation. METHODS: Neonatal screening for haemoglobinopathies was universal, performed using liquid cord blood and an isoelectric focusing technique. All samples with abnormalities underwent confirmatory testing. Major and minor haemoglobinopathies were reported. Affected children were referred to a specialist centre. A central database in which all screening results were stored was available and accessible to local care workers. A central clinical database to monitor follow-up is under construction. RESULTS: A total of 191,783 newborns were screened. One hundred and twenty-three (1:1559) newborns were diagnosed with sickle cell disease, seven (1:27,398) with beta thalassaemia major, five (1:38,357) with haemoglobin H disease, and seven (1:27,398) with haemoglobin C disease. All major haemoglobinopathies were confirmed, and follow-up of the infants was undertaken except for three infants who did not attend the first medical consultation despite all efforts. CONCLUSIONS: The universal neonatal screening programme was effective because no case of major haemoglobinopathy was identified after the neonatal period. The affected children received dedicated medical care from birth. The screening programme, and specifically the reporting of minor haemoglobinopathies, has been an excellent health education tool in Belgium for more than 12 years.

[Infantile pyknocytosis: a rare form of neonatal hemolytic anemia. 5 case-studies]. / La pyknocytose infantile : une anémie néonatale mal connue à propos de 5cas.

UNLABELLED: Infantile pyknocytosis (IP) is a rare hematological entity of newborns. It is a form of hemolytic anemia with unusual red cell morphology: the red blood cells are distorted, irregular, and small with many projections. Spontaneous resolution usually occurs by 4-6months of age. OBSERVATION: We describe the clinical features and biological parameters of 5 cases of IP. The first symptoms were always early jaundice, which required phototherapy. Anemia was severe in all babies and red blood cell transfusion was needed. CONCLUSION: IP is a rare cause of neonatal anemia whose diagnosis is based on a careful peripheral blood smear examination. In our study, anemia was severe and required red blood cell transfusion. Ethnic specificity and familial occurrence are reported in our experience.

[Management of medulloblastoma in children: the experience of a single institution in Liege from 1991 to 2005]. / Prise en charge du médulloblastome de l'enfant.

We present the experience of the Citadelle Hospital (Liege, B) in the diagnosis, treatment and follow-up of medulloblastoma in children. A retrospective study of 10 cases of medulloblastoma was performed. Five years after diagnosis, the event-free survival was 77%.

[Secondary cancers in childhood]. / Faut-il craindre l'apparition d'un second cancer en pédiatrie?

Improved survival of pediatric cancer patients will lead to an increase of late sequellae such as secondary malignant neoplasms (SMN). Specific pediatric factors predisposing to these SMN are as follows: long expecting duration of life, high cellular proliferative potential, toxicity of often combined cancer therapies (radio- and chemotherapies) and more frequent genetic predisposition to cancer. Better understanding of these factors could improve patients management and could lead to the development of less toxic future therapies with the hope to decrease the risk of SMN.

[Sickle cell disease: exotic disease or a Belgian public health problem?]. / La drépanocytose: une affection exotique ou un problème de santé publique en Belgique?

Sickle cell disease is a genetic disorder involving the haemoglobin designated as haemoglobin S, an autosomic recessive hereditary disease. It is the most frequent hereditary disease in sub-Saharan Africa, however epidemiological studies performed with a systematic neonatal screening in Brussels and Liège have proven that more than one neonate over 2.000 has a sickle cell disease. If this amount is significant, at the level of each physician the number of patient-contacts will be weak. Another aspect of the disease is the variability in its expression: some patients suffer from multiple and chronic organ alterations while other suffer also from acute events which might lead to death if not treated appropriately. The poor experience of each physician, the lack of the disease knowledge by the population, the symptoms complexity, and the socio-economical aspects of sickle cell disease explain that it can be considered as an "exotic" disease but also as a public health problem. A global and dedicated approach of the patient as a whole must be implemented. This is the reason for the existence of the "Réseau des Hémoglobinopathies": http://www.redcellnet.be/.

[Clinical evaluation of 23 children with neuroblastoma. The experience of a single institution]. / Les neuroblastomes de l'enfant. A propos de 23 cas.

In this retrospective study, we analyse epidemiology, clinical symptoms and therapeutic results in a group of 23 children with neuroblastoma. Half of them were less than 2 years of age; in 19 of 23, the primitive tumour was abdominal; 35% of them were initially metastatic. The overall survival was 83% at 5 years and the event free survival, 75% at 5 years. Pronostic factors are age, extension of the disease at diagnosis, biologic parameters and genetic study of the neuroblast cells (amplification of N-myc oncogen). Our study shows the deleterious effect of bone lesions.

Value of intravenous 6-mercaptopurine during continuation treatment in childhood acute lymphoblastic leukemia and non-Hodgkin's lymphoma: final results of a randomized phase III trial (58881) of the EORTC CLG.

Between November 1990 and November 1996, EORTC Children Leukemia Group conducted a randomized trial in de novo acute lymphoblastic leukemia and lymphoblastic non-Hodgkin's lymphoma patients using a Berlin-Frankfurt-Munster protocol to evaluate the monthly addition of intravenous 6-mercaptopurine (i.v. 6-MP) (1 g/m(2)) to conventional continuation therapy comprising per oral MTX weekly and 6-MP daily. Only during the first 18 months of the randomization period, 6-MP p.o. was interrupted for 1 week after each i.v. 6-MP. A total of 877 patients was randomized to either no i.v. 6-MP (Arm A) or additional i.v. 6-MP (Arm B). A total of 217 relapses (91 in Group A vs 128 in Group B) and 13 deaths in CR (5 vs 8) were reported; a total of 134 patients (55 vs 79) died. The median follow-up was 7.6 years. At 8 years, the disease-free survival rate was lower (P=0.005) in Arm B (69.1% (s.e.=2.2%)) than in Arm A (77.9% (s.e.=2.0%)), and the hazard ratio was 1.45 (95% CI 1.12-1.89). In conclusion, as delivered in this study, i.v. 6-MP was detrimental to event-free survival.