[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.

[Bone disorders and complications of pediatric acute lymphoblastic leukemia : monocentric study and review of the literature]. / Atteintes osseuses des leucémies lymphoblastiques aiguës pédiatriques : expérience monocentrique et revue de la littérature.

Bone pain associated with bone marrow infiltration is often present at diagnosis of pediatric acute lymphoblastic leukemia (ALL). It sometimes signs the presence of pathological fracture, lytic lesions, arthritis, or osteitis associated to ALL that can delay the diagnosis. During treatment, bone complications (pain, osteopenia, fracture, avascular necrosis, ...) are also reported. In order to describe bone involvement (BI) of pediatric LLA, we reviewed the records of 104 patients followed in our unit. The overall incidence of BI was 67 %. At diagnosis, 50 % of patients had BI and in 19 %, the diagnosis of ALL was delayed. During and after treatment, respectively 28 % and 37 % of patients presented bone complications (pain, fractures, avascular necrosis, osteopenia). Patients with BI had a lower leukocytosis inferior to 10x109/l (p = 0.005) and an ALL of average risk (p = 0.019). 38 % of patients with BI during treatment were over 10 years old and 55 % were girls (vs. 21 % and 38 % in the entire cohort, respectively). Osteoporosis was more severe at diagnosis than during treatment, suggesting the presence of constitutional promoting factors. In our cohort, the majority of BI was resolved at the end of treatment with no long-term sequelae.

Des douleurs osseuses sont souvent présentes au diagnostic des leucémies lymphoblastiques aiguës (LLA) pédiatriques. Elles signent aussi parfois la présence de fracture pathologique, de lésions lytiques, d'arthrite, ou d'ostéite associées qui peuvent retarder le diagnostic. Lors des traitements, des complications osseuses (douleurs, ostéopénie, fracture, nécrose avasculaire, …) sont également rapportées. Afin de décrire les atteintes osseuses (AO) des LLA pédiatriques, nous avons revu les dossiers de 104 patients suivis dans notre unité. L'incidence globale des AO était de 67 %. Au diagnostic, 50 % des patients avaient une AO et, chez 19 % d'entre eux, le diagnostic de LLA a été retardé. Pendant et après les traitements, respectivement 28 et 37 % des patients ont présenté des complications osseuses (douleurs, fractures, nécrose avasculaire, ostéopénie). Les patients avec AO avaient une leucocytose plus basse inf�rieur a 10x109/l (p = 0,005) et une LLA de risque moyen (p = 0,019). Chez les patients avec AO pendant les traitements, 38 % avaient plus de 10 ans et 55 % étaient des filles (vs 21 % et 38 % dans la cohorte entière). L'ostéoporose était plus sévère au diagnostic que pendant les traitements, suggérant la présence de facteurs favorisants constitutionnels. Dans notre cohorte, la majorité des AO étaient résolues après les traitements de LLA sans séquelles à long terme.

CNS-3 status remains an independent adverse prognosis factor in children with acute lymphoblastic leukemia (ALL) treated without cranial irradiation: Results of EORTC Children Leukemia Group study 58951.

AIM: To evaluate the prognostic significance of initial central nervous system (CNS) involvement of children with acute lymphoblastic leukemia (ALL) enrolled in the EORTC 58951 trial. PATIENTS AND METHODS: From 1998 to 2008, 1930 ALL patients were included in the randomized EORTC 58951 trial. Overall treatment intensity was adjusted according to known prognostic factors including the level of minimal residual disease after induction treatment. CNS-directed therapy comprised four to 11 courses of i.v. methotrexate (5g/m2), and 10 to 19 intrathecal chemotherapy injections, depending on risk group and CNS status. Cranial irradiation was omitted for all patients. RESULTS: The overall 8-year event-free survival (EFS) and overall survival (OS) rates were 81.3% and 88.1%, respectively. In the CNS-1, TPL+, CNS-2, and CNS-3 groups, the 8-year EFS rates were 82.1%, 77.1%, 78.3%, and 57.4%, respectively. Multivariable analysis indicated that initial CNS-3 status, but not CNS-2 or TLP+, was an independent adverse predictor of outcome. The 8-year incidence of isolated CNS relapse was 1.7% and of isolated or combined CNS relapse it was 3.7%. NCI high-risk group, male sex, CNS-2 and CNS-3 status were independent predictors for a higher incidence of any CNS relapse. CONCLUSIONS: CNS-3 status remains associated with poor prognosis and requires intensification of both systemic and CNS-directed therapy. This trial was registered at https://clinicaltrials.gov/under/NCT00003728.

A not so harmless mass: Kaposiform hemangioendothelioma complicated by a Kasabach-Merritt phenomenon.

A vascular mass localized in the face and the neck was displayed by ultrasonography in a 38-week-old male fetus. At birth, the mass was bulky and purplish. The newborn breathed spontaneously but with severe desaturation. During laryngoscopy, we observed an obstruction of the larynx with a left-shift caused by the hemorrhagic mass. Blood analysis revealed anemia, severe thrombocytopenia, and coagulation disorders. The diagnosis of kaposiform hemangioendothelioma (KHE) complicated by a Kasabach-Merritt phenomenon (KMP) was put forward and treatment with propranolol, corticoids, and vincristine was initiated. Platelets were transfused daily for 8 days but did not resolve the thrombocytopenia. At day 8, we added sirolimus to the treatment and noted a rapid response with the normalization of the platelet count within 1 week and a significant regression of the mass. In this paper, we review the clinical and biological features of hemangioendothelioma associated with KMP and discuss its current and future treatment. Sirolimus seems to be very promising.

[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.

[Vincristine treatment for management of alarming hemangiomas in infancy]. / La vincristine: nouveau traitement des hémangiomes infantiles?

Hemangioma is the most benign vascular tumor encountered in infancy; its incidence is 10-12% at 1 year of age. It usually appears a few weeks after birth, and rather rapidly grows until the age of 10-12 months; it then stabilizes and spontaneously regresses towards a complete disappearance over 5 - 10 years. Therefore, most hemangiomas need no treatment, but just a close clinical follow up. However, some hemangiomas (10-20% of cases), because of their location and/or complications, can have very serious aesthetic, functional, or even vital consequences: these require a more aggressive approach. A pharmacologic initial therapy based on high doses of corticosteroids or interferon alpha 2a or 2b has gained wide acceptance, but can entail serious side-effects. Vincristine represents a safe and effective treatment option for the management of those alarming hemangiomas.

[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%.

[A new treatment for vascular anomalies: Six cases treated with rapamycin]. / Une nouvelle approche thérapeutique des malformations vasculaires à faible débit : la rapamycine ­ à propos de 6 cas.

Vascular anomalies (VAs) result from the defective development of the embryonic vascular system and feature dysplastic malformed vessels, which are not always apparent at birth. They do not regress over the patient's lifetime; they usually have commensurate growth during childhood and may worsen over time if not treated. VAs may cause chronic painful swelling, bleeding, functional deficits or vital structure obstruction. These patients' quality of life is usually impaired because of the chronicity and recurrence of the disease. We report on six cases of complicated VAs, refractory to current treatments, treated with rapamycin, an mTor inhibitor recently used in VAs.

Results of 58872 and 58921 trials in acute myeloblastic leukemia and relative value of chemotherapy vs allogeneic bone marrow transplantation in first complete remission: the EORTC Children Leukemia Group report.

The first EORTC (European Organization of Research and Treatment of Cancer) acute myeloblastic leukemia (AML) pilot study (58872) was conducted between January 1988 and December 1991. Out of 108 patients, 78% achieved complete remission (CR), and event-free survival (EFS) and survival rates (s.e., %) at 7 years were 40 (5) and 51% (6%), respectively. It indicated that mitoxantrone could be substituted for conventional anthracyclines in the treatment of childhood AML without inducing cardiotoxicity. The aim of the next EORTC 58921 trial was to compare the efficacy and toxicity of idarubicin vs mitoxantrone in initial chemotherapy courses, further therapy consisting of allogeneic bone marrow transplantation (alloBMT) in patients with an HLA-compatible sibling donor or chemotherapy in patients without a donor. Out of 177 patients, recruited between October 1992 and December 2002, 81% reached CR. Overall 7-year EFS and survival rates were 49 (4) and 62% (4%), respectively. Out of 145 patients who received the first intensification, 39 had a sibling donor. In patients with or without a donor, the 7-year disease-free survival (DFS) rate was 63 (8) and 57% (5%) and the 7-year survival rate was 78 (7) and 65% (5%), respectively. Patients with favorable, intermediate and unfavorable cytogenetic features had a 5-year EFS rate of 57, 45 and 45% and a 5-year survival rate of 89, 67 and 53%, respectively.

[Rectal prolapse revealing a tumor: The role of abdominal ultrasound]. / Prolapsus rectal révélant une tumeur : intérêt de l'échographie abdominale, à propos de 3 cas.

Rectal prolapse is rare in children and usually benign. However, there are various diseases that can be associated with it, such as cystic fibrosis or other causes of increased abdominal pressure. Here, we review the various underlying conditions that pediatricians or pediatric gastroenterologists should consider in the case of rectal prolapse. We report on three cases of children with a rectal prolapse and intra-abdominal tumors. Current recommendations and practice do not include a systematic check via abdominal imaging in cases of rectal prolapse. However, in some situations, imaging is indicated to detect a possible expansive process. Thus, in the presence of recurrent prolapse or of associated urinary or neurological signs, imaging is justified so as to allow for an early diagnosis and treatment of these neoplasms. Given its lack of radiation exposure and good sensitivity in children, ultrasound imaging is the first choice.

[Retrospective study of childhood lymphomas. Report of 27 children treated at a single institution]. / Etude rétrospective des lymphomes de l'enfant. A propos de 27 cas traités dans une même institution.

Childhood lymphomas represent a heterogeneous group of disorders that are quite different from adult lymphomas. Over the past three decades, empirical chemotherapeutic management has transformed survival figures, and more recently greater understanding of the biology is offering hope for improved management of resistant disease. We present here the experience of a single institution in the management of 27 childhood lymphomas; epidemiological and clinical characteristics are described as well as survival rates. The median follow up of the patients is 4 years 7 months. The five-year overall survival for the entire group is more than 95 %; the 5-year disease free survival is 91,6 % for Hodgkin's lymphomas, 92,8% for non Hodgkin's lymphomas and 100% for Burkitt diseases. Two relapses have occurred and all of them appeared within the 18 months of the diagnosis. No toxic death has been reported.

Nasal heterotopia versus pilocytic astrocytoma: A narrow border.

Failure of the anterior neuropore can lead to three main types of anomalies: nasal dermal sinus, encephalocele and nasal glioma or heterotopia. In this report, we describe a case of intracranial and extracranial glial heterotopia that probably resulted from a common failure of anterior neuropore development. We describe the prenatal radiological assessment based on ultrasound and MRI results, and consider their limitation for early fetal diagnosis. We also discuss the embryogenesis and the possible pathogenic mechanisms involved.

Chronic bronchopulmonary disease and gastroesophageal reflux in children.

Fifty-four children who had chronic bronchopulmonary disease (CBPD) were investigated for the incidence of gastroesophageal reflux (GER). An activity score for CBPD and a numerical reflux score using criteria from a pH probe study were established. Results of barium esophagography, endoscopy, and prolonged esophageal pH probe monitoring were abnormal in 67, 78, and 53% of the patients, respectively. A significant relationship was found between the CBPD activity score and the reflux score; this strongly suggests that, in the patients studied, GER was responsible for the bronchopulmonary symptoms. Antireflux therapy resulted in an improvement of the CBPD activity score in all patients who had abnormal reflux scores. The mean CBPD activity score was 4.4 and 1.3 before and after antireflux therapy, respectively (P less than 0.01). Most patients who had normal reflux scores did not improve on antireflux therapy.

Intestinal permeability to chromium-51 ethylenediamine tetraacetic acid in children with chronic obstructive respiratory disease: relationship with clinical and duodenal biopsy findings.

Intestinal permeability (IP) to 51-Cr ethylenediamine tetraacetic acid was investigated in 47 children with chronic obstructive respiratory disease (CORD). Endoscopic duodenal biopsies were performed in 22 of these patients. IP was significantly increased in CORD patients when compared to either control children or adults (P less than 0.001). Mean +/- 1 SD were 4.3 +/- 1.71%, 2.5 +/- 0.78%, and 2.3 +/- 0.77% in the three groups, respectively. IP was not related to the presence of atopy. Significant differences in IP results were found between CORD children with abdominal pain (4.5 +/- 1.4%) and both control children and CORD patients without abdominal pain (2.5 +/- 0.78% and 3.2 +/- 1.49%, respectively). A significant correlation was found between small bowel injury on the one hand and IP on the other hand (P less than 0.02). Furthermore, small bowel injury was significantly related to the presence of abdominal pain (P less than 0.05). We speculate that in CORD patients with abdominal pain, a factor exists that causes small bowel injury responsible for both abdominal pain and increased small bowel permeability. Food intolerance could, presumably, play a role in the mucosal damage-linked IP increase found in the subset of CORD patients who complain of abdominal pain.

[Sickle cell anemia in children: value of hydroxyurea in severe forms]. / Anémie falciforme chez l'enfant: intérêt de l'hydroxyurée dans les formes graves.

BACKGROUND: Sickling of red cells in patients with sickle cell anemia causes painful vaso-occlusive crises (VOC). Hydroxyurea (HU) has been shown to increase HbF production and therefore has the potential to prevent these crises in adult patients. This work aimed to confirm its clinical efficiency in children. PATIENTS AND METHODS: Since 1993, eight children and adolescents (5-16 years old) with hemoglobinopathy (HbS > 65%) were given HU (14 to 27 mg/kg/day) for a mean duration of 10 months. We did a retrospective study about different data, especially inpatient days for VOC, pain intensity during these crises, individual transfusion requirements and HbF level. RESULTS: As the HbF levels increased, we observed a reduction of the inpatient days for VOC, of the pain intensity during these crises and of the mean number of units transfused per month. CONCLUSION: HU is the first clinically acceptable drug shown to prevent painful crises in adults but also in children with sickle cell anemia. However, its effects and potential toxicity are still unknown and the other therapeutic possibilities have to be considered before starting a long-term treatment with HU.

[Chronic visceral leishmaniasis during chemotherapy for metastatic osteosarcoma]. / Leishmaniose viscérale chronique au cours d'une chimiothérapie pour ostéosarcome métastatique.

UNLABELLED: Leishmaniasis refers to a spectrum of diseases caused by Leishmania. Clinically, three types of leishmaniasis can be distinguished: the cutaneous, mucous and visceral leishmaniasis, the latter being caused by Leishmania donovani. CASE REPORT: An 11-year-old Thai, living in Belgium for 6 years, had surgery for a vertebral osteosarcoma with pulmonary metastases, followed by polychemotherapy, then pulmonary metastasectomy. During a post-chemotherapy bone marrow aplasia, febrile episode with a general condition impairment was noted and first treated by broad-spectrum antibiotherapy, then by amphotericin B, in the absence of any accurate etiology. The outcome first was favorable. Nevertheless, 7 months later, the visceral leishmaniasis diagnosis was made because of the recurrence of the same symptoms. Classical treatments by antimony derivatives (Glucantim), then liposomal amphotericin (Ambisome) proved to be inefficient. A liposomal amphotericin-gamma interferon association suppressed the symptoms without eradicating the parasite. The patient was given a maintenance therapy based on liposomal amphotericin. CONCLUSION: The stubborn and recurring nature of this chronic visceral leismaniosis can be due to the immune deficit inherent in the polychemotherapy performed in order to treat the metastatic osteosarcoma which currently is in first full remission.

[Arterial aneurysm within a tumor in a pediatric patient]. / Anévrisme artériel intra-tumoral chez l'enfant.

A middle cerebral artery aneurysm, completely enclosed in a large frontotemporal anaplastic astrocytoma, is demonstrated in a 11-month-old girl admitted for intracranial hypertension. Clipping of the aneurysm along with radical resection was successfully performed. Five years later, follow-up neurological examination is normal, aneurysm occlusion and no evidence of tumor recurrence are demonstrated by angiogram and MRI. The association of brain tumor and aneurysm is discussed, and documented with the only two cases of a neoplasm surrounding on aneurysm reported in the literature.

[Mixed connective tissue disease in childhood: report of two clinical cases]. / Les connectivites mixtes chez l'enfant: illustration par deux cas cliniques.

Sharp's syndrome, or mixed connective tissue disease, is an autoimmune chronic disease characterized by a tissue collagen abnormality. It is more common among young women, but is also described in children. The symptomatology may be different from one case to another as shown in the two presented cases. Signs and symptoms of other rheumatic diseases are commonly observed. The presence of anti-RNP antibody is requested to confirm the diagnosis. The treatment is adapted to each individual. Non-steroidal anti-inflammatory drugs, corticosteroids, and immunosuppressive drugs are the basis of treatment.

[Perinatal HIV transmission prophylaxis in the Liege region]. / Prophylaxie de la transmission périnatale du HIV en région liégeoise.

In Liège, since February 1994, Protocole ACTG 076 has been followed for prevention of perinatal transmission of VIH. The pregnant women are treated by AZT during pregnancy and delivery. The newborn is also treated during 6 weeks. Following this treatment strategy, vertical transmission rate of VIH has dropped from 25.6% to 8.7%. The PCR is particulary promising for the early detection of infection in newborn, but definitive conclusion about infective status of the newborn can't be done during the first week of life. The potential role of intrapartum transmission is now under evaluation in the hope to establish the safest mode of delivery.

[Guidelines for the management of patients with HIV infection. II. Pregnant women and children. Liege Working Group on HIV Infection]. / Recommandations pour la prise en charge du patient infecté par le VIH. II. La femme enceinte et l'enfant. Groupe de Travail de Liège sur l'Infection par le VIH.

The management of the HIV infected child is nearly identical to the adult. Nevertheless, there are many clinical, immunological and virological details. Difficulties evoked for the adult have an even bigger importance, in view of the foreseeable longevity of these children under treatment. The reduction of the mother to child transmission, thanks to the AZT-caesarean association, must be continued. The use of anti-retroviral drugs during pregnancy requires a sustained attention because of the potential risks and benefits for the foetus and mother. The long-term impact of these drugs, in children exposed during pregnancy, remains unknown. The follow-up of these children therefore remains important.