Invasive aspergillosis and allogeneic hematopoietic stem cell transplantation in children: a 15-year experience.

Despite progress in diagnosis and treatment, invasive aspergillosis (IA) remains a principal cause of mortality due to infection after allogeneic hematopoietic stem cell transplantation (AHSCT). In order to clarify the course of IA among children receiving an AHSCT before the advent of new drugs such as voriconazole or caspofungin, we retrospectively reviewed the medical records of all proven and probable IA between January 1986 and December 2000. 1) Ten children developed IA after AHSCT, mostly long after transplantation. Overall incidence was 2.7%. Seven of those children experienced 1 or more complications after AHSCT and before IA. Mortality was 90% with a median survival of 23 days (2-90). 2) Five children underwent AHSCT after a previous episode of IA. All patients were treated with systemic antifungal therapy combined with surgery. Median time between IA and AHSCT was 110 days (73-370). Two children were diagnosed with IA relapse after transplantation. One child was cured while the other died of IA and AHSCT complications. AHSCT could be considered even in the setting of previous IA, but established strategies implementing newer less toxic antifungal agents as treatment or prophylaxis in high-risk patients are needed.

Does nephroblastomatosis influence the natural history and relapse rate in Wilms' tumour? A single centre experience over 11 years.

The presence of multifocal or diffuse nephrogenic rests (NRs) in one or both kidneys is termed nephroblastomatosis (Nbm). Nbm may be a predisposing factor for Wilms' tumour (WT). The aim of this retrospective study was to evaluate the impact of Nbm on the outcome of WT in children. We assessed the outcome of 81 children with Wilms tumours and practical implications of Nbm in the treatment and follow-up. All the pathology slides have been reviewed in 1997. 63 had WT without Nbm (group A) and 18 had WT associated with Nbm (group B). There was no statistical difference between the two groups according to the age at diagnosis and histology. Clinical abnormalities were more frequent in group B (33 versus 8%). There was no statistical difference between the percentage of stage IV in both groups, but bilaterality (stage V) was present only in the group B. Relapse was observed in 20/81 patients (25%): 11 (17%) in group A and 9 (50%) in group B. Mean delay of relapse was longer (25 months) in group B than in group A (10 months). For the whole population, with a median follow-up of 9 years, the event-free survival (EFS) and the overall survival (OS) probabilities were respectively 74%+/-10 and 83%+/-9 at 120 months. The difference in EFS between groups A (82+/-9%) and B (38%+/-29) was significant (P=0.004). The discovery of Nbm in the non-tumoral part of the kidney with WT can be an adverse factor and in particular favours the subsequent development of a new Wilms tumour. It justifies separate follow-up guidelines.

Epstein-Barr virus-related lymphoproliferative disease complicating childhood acute lymphoblastic leukemia: no recurrence after unrelated donor bone marrow transplantation.

A 16-year-old boy in complete remission of ALL, undergoing oral maintenance therapy, developed intestinal perforation related to EBV-associated lymphoproliferative disease (LPD). He was successfully managed with surgical resection, acyclovir, immunoglobulins and discontinuation of maintenance therapy. Leukemic marrow relapse occurred 3 months later, treated by polychemotherapy followed by unmanipulated BMT from a matched unrelated EBV seropositive donor. Donor lymphocytes were infused twice after transplant because of delayed immunologic recovery and severe CMV colitis. This was followed by acute GVHD requiring prolonged immunosuppressive treatment. Despite intensive and prolonged immunosuppression, recurrence of LPD was not observed. Following EBV-related LPD, allogeneic BMT can be performed if indicated. Selection of an EBV seropositive donor is of major importance for the prevention of LPD recurrence as the recipient may be protected by passive transfer of EBV-specific cytotoxic T cells.

Abdominal inflammatory myofibroblastic tumors in children: report of an appendiceal case and review of the literature.

Inflammatory myofibroblastic tumors (IMT) are rare, benign lesions. They mimic, clinically and radiologically, malignant tumors-especially sarcoma. IMT most often are seen in the lung of young adults, but there have been reports of these tumors occurring in children, in various sites. The authors report a case of appendiceal IMT arising in a 15-year-old boy previously treated for inherited distal renal tubular acidosis. He was admitted because of anorexia, weight loss, and a low-grade fever. The ultrasound study showed bilateral hydroureteronephrosis, with a poorly functioning right kidney noted on intravenous urography, and a retrovesical soft-tissue mass. Laboratory studies showed renal insufficiency, an elevated white blood cell count, anemia, thrombocytosis, and hypergammaglobulinemia. During laparotomy, a pelvic appendiceal mass was discovered, appendectomy was performed, and the pathological diagnosis of inflammatory myofibroblastic tumor was made. Three months later the boy was well, and the biological, sonographic, and urographic results had returned to normal. A review of 74 cases of abdominal IMT occurring in childhood emphasizes the importance of pathological differentiation of these lesions from malignancy, with early total excision whenever possible. Long-term follow-up is necessary to detect local recurrence, which may develop many years later, and to confirm the allegedly benign nature of these tumors.

Juvenile granulosa cell tumor of the ovary in infants: a clinicopathologic study of three cases and review of the literature.

The clinical and pathological features of three cases of juvenile granulosa cell tumors occurring in infants were studied. Precocious pseudopuberty developed in two patients and acute abdominal symptoms related to the rupture of the tumor developed in one. Surgery was the only treatment in each case and no adjuvant therapy was delivered. No patient experienced relapse. Histological examination showed a predominantly diffuse pattern with prominent luteinization. Call-Exner bodies were absent. Two tumors had multilocular thin walled cysts containing large amounts of estradiol, the third one contained rudimentary microfollicles. The prognosis of juvenile granulosa cell tumors in infancy appears more favorable than those occurring in older patients. No case of tumor recurrence has been reported in infancy so far. Surgery appears to be the state-of-the-art treatment of these tumors and additional therapy (chemotherapy or radiotherapy) must be discussed with caution, even in advanced stages.

[Unusual relapse for neuroblastoma. Case of an intracranial relapse]. / Rechute inhabituelle de neuroblastome. A propos d'une récidive intracrânienne.

The usual sites of initial metastatic deposits in neuroblastoma are osteo-medullary. With modern therapies including megatherapy and hematopoietic rescue, prolonged survival is obtained. However, unusual metastatic sites are more and more often described during the prolonged evolution of these patients such as brain metastases. A case of isolated intracerebral metastatic relapse is reported here in a patient who had received 4 months before a megatherapy in first complete remission. Pathogeny and therapeutical implications are discussed.

[Gastric trichobezoar in an adolescent presenting with anemia: ultrasound and MRI findings]. / Trichobézoard gastrique révélé par une anémie chez une adolescente: association échographie--imagerie par résonance magnétique (IRM).

Trichobezoars are rare and composed of ingested hair or fibers. Diagnosis is usually made by plain radiographs and barium meal. The usefulness of computed tomography has been reported in the preoperative period. In the pediatric population the authors propose, based on a recent case report, a non invasive and non irradiating protocol using sonography and T1W and T2W MR imaging.

[Acute gastric distension necessitating gastrostomy after anesthetic induction for surgical correction of type III esophageal atresia]. / Distension gastrique aiguë nécessitant une gastrostomie après induction anesthésique pour correction chirurgicale d'une atrésie de l'oesophage de type III.

IPPV during anaesthesia for management of oesophageal atresia with tracheo-oesophageal fistula (TOF) can cause gastric insufflation. We report such a complication in a one-day-old newborn, who developed, 15 min after induction, a distension of the abdomen, hypoxia and bracdycardia. An emergency gastrostomy was performed. His status improved rapidly and surgery could be completed. TOF was located at the carina and had a large calibre. To avoid gastric distension in such cases, the tip of the tube is located just proximal to the carina, but distal to the fistula to prevent intubation of the latter. Difficulties are due to position of the fistula (carina, main bronchi) or its large bore. Gastric distension carries a risk of regurgitation and inhalation of gastric contents, elevation of hemidiaphragm and lung compression, decreased tidal volume, decreased venous return, cardiovascular collapse and cardiac arrest. When insufflation peak pressures are low, gastrostomy is benefitful, as in our case, as the tidal volume loss through the stomach is acceptable. In case of high insufflation pressures because of co-existing lung disease, gastrostomy is better avoided, as most if not all the tidal volume may be lost through the stomach.

[Acute cannabis poisoning in a 10-month-old infant]. / Intoxication aiguë par cannabis chez un nourrisson de 10 mois.

We describe a case of accidental cannabis poisoning in a 10-month-old girl, who presented with impaired consciousness, with drowsiness and restlessness, generalized hypotonia, and inadequate smiles. No circulatory or respiratory problems were observed. Initial investigations were not informative (blood biology, CT scan, and cerebrospinal fluid examination), while the main causes of coma (meningoencephalitis, head trauma, metabolic disorders) were excluded. Questioning the parents led to suspecting accidental ingestion of a piece of cannabis, which was confirmed by the detection of high blood and urine levels of cannabinoid derivatives. Management was symptomatic and the clinical course, marked by the occurrence of agitation and irritability episodes lasting up to H18, led to complete regression of symptoms. Because of the high consumption in France, pediatric poisoning by cannabis seems increasingly common. The toxic levels in children are unknown however. Diagnosis is based on questioning and the search for cannabinoid derivatives in urine. In children, clinical symptoms are more expressive compared to adults, with neurological (drowsiness, agitation, abnormal behavior, ataxia, hypotonia, coma, and convulsions) or cardiopulmonary (tachycardia, bradypnea, apnea) or homeostatic presentations (hypothermia). Treatment in children is essentially symptomatic but sometimes requires active resuscitation. Recommendations are based on clinical monitoring the first 24h after intoxication and on medicosocial support.

Investigation of PK-PD drug-drug interaction between acenocoumarol and amoxicillin plus clavulanic acid.

A pharmacokinetic-pharmacodynamic (PK-PD) drug-drug interaction between acenocoumarol and amoxicillin + clavulanic acid antibiotic was assessed in eight healthy volunteers, using a population PK-PD) model. Each subject received at day 1 a single dose of 8 mg of acenocoumarol. Then 1 g of amoxicillin + 250 mg of clavulanic acid was given from days 3 to 9. On day 8, each subject received a single dose of 8 mg of acenocoumarol concomitantly with the antibiotic combination. Eleven blood samples were taken during 48 h following each acenocoumarol administration. Acenocoumarol plasma concentrations and prothrombin time were measured at each sampling time. We first identified the structural PK model by pooling data from this trial with individual data from other acenocoumarol PK trials. An indirect response model was used to fit PD data. Models were built using a non-linear mixed effect modelling approach with nonmem software. Covariates were tested on PK and PD parameters, including antibiotic treatment. Acenocoumarol PK data were fitted by a two-compartment, first-order input model with log normal inter-individual variability. Weight and antibiotic treatment were found to improve significantly the fit of PK data with a 15% decrease in acenocoumarol clearance with concomitant antibiotics (P < 0.05). An indirect response model was successfully applied to the PK-PD data of acenocoumarol. No covariate, including antibiotic treatment effect, significantly affected PT. Drug-drug interaction was demonstrated at the PK level, without any PD corollary.

[10 years' experience with intermittent catheterization in neurogenic bladder in children and adolescents: study of 165 cases]. / Dix ans d'expérience avec le cathétérisme intermittent dans les vessies neurologiques de l'enfant et de l'adolescent: étude de 165 dossiers.

Intermittent clean catheterization has been proposed in 1975 for the treatment of neurogenic bladder in children and teen-agers. We report results in 165 patients with neurogenic bladder (111 girls, 54 boys) from 1976 to 1986; 9 patients were lost for follow-up. Myelomeningocele was the cause of the neurogenic bladder in 132 cases. The effects on continence, upper-tract and urinary infection are studied. These data show that such a method is simple, harmless and effective for the protection of the upper urinary tract and for the control of urinary incontinence.

[Transappendicular continent cystostomy. Critical study apropos of 30 cases]. / Cystostomie étanche trans-appendiculaire. Etude critique à propos de 30 observations.

UNLABELLED: Continent vesicostomy using appendix has been performed in 30 incontinent children (myelo-meningocele). Surgical technique is described laying stress on the closure of the bladder neck and the appendix arrangement: appendix is implanted in the bladder with an antireflux sub-mucosal tunnel and the other end is hemmed to the skin. Self-catheterization is very easy. All patients are dry but the rate of complications was very high: 77%--8 leakage through the bladder neck imposing one or two re-operations. 10 uretero-hydronephrosis related to a small and hypertonic bladder: enterocystoplasty with good results--5 lithiasis--2 perforations. Success of this technique is closely linked to the construction of a large and low pressure bladder: 11 enterocystoplasty have been performed secondarily and 4 during the first operation. Actually 26/30 patients are well with normal kidneys and excellent comfort. FOLLOW-UP: 1 to 7 years.

[Treatment of hypospadias]. / Le traitement de l'hypospade.

The aim of surgery for hypospadias is to reconstruct in one stage, at about 2 years of age, a penis that will be functionally and cosmetically, as close to normal as possible. We described the various techniques that we use depending on the degree of meatal ectopia and the presence or absence of chordee. We have treated hypospadia that is strictly glandular either with Duckett's Magpi procedure (54 cases, 49 long-term follow-up, 47 good results, retraction of the meatus in two), or Koff's advancement procedure if there is a grow in glans (13 cases, 12 good results, on requiring meatostomy). Although these meatoplasties do give good results, they hide the malformation rather than correct it and must therefore be reserved for those forms that are strictly glandular. We have treated coronal and distal shaft hypospadias without chordee by the technique of Mathieu combined with the Byars method of coverage (50 cases, 4 fistulae successfully corrected at a second one-day surgery, no stenosis--only one poor cosmetic result. In all other form of hypospadias one must first correct the chordee. The incision and the correction of the various elements that contribute to the chordee are described in detail. After straightening if the meatus is distal to the mid-point of the phallus the Devine-Horton "flip-flap" procedure is used (240 cases, 17 fistulae, (17%), 10 meatal stenosis (4%), 95 excellent cosmetic result). If, after straightening, the meatal opening is proximal to the phallus grafting is necessary.(ABSTRACT TRUNCATED AT 250 WORDS)

[Impact of reflux on the kidney]. / Le retentissement du reflux sur le rein.

Description of the reflux nephropathy. Pyelonephritis lesions are undoubtedly linked to the vesico-ureteric reflux. The role of the intra-renal reflux ( Hodson ) and the Big Bang Theory ( Ransley ) are discussed as the data from animal experiments. The role of the sterile reflux and of the segmental hypoplasia is relatively less important. The actual management of vesico-ureteric reflux treatment is questioned.