Long-term morbidity and mortality in 2-year hepatoblastoma survivors treated with SIOPEL risk-adapted strategies.

BACKGROUND AND AIMS: Prognosis of hepatoblastoma patients has increased with cisplatin-based chemotherapy and high-quality resection including liver transplant. Consequently current risk-adapted therapeutic strategy aims to reduce long-term side effects in patients with standard risk disease. METHODS: We report long-term mortality and morbidity data concerning 151 2-year hepatoblastoma survivors treated with SIOPEL risk-adapted strategies (sex-ratio M/F = 1.6, median age at diagnosis = 2.6 years [range 0-17.7], median year at diagnosis = 2008 [1994-2017]). Fifty-three patients had loco-regional risk factors VPEFR, 12 were PRETEXT-IV and 30 were metastatic. All received cisplatin and 84 anthracyclines. Twelve had liver transplant. To assess hearing, renal and cardiac functions, audiograms were performed in 116/151 patients (76.8%), glomerular filtration rate in 113/151 (74.8%) and cardiac ultrasound in 65/84 (77.4%) anthracycline-exposed patients. RESULTS: With a median follow-up of 9.4 years (range 2.1-25.8), four late relapses, one second malignancy (Acute Myeloid Leukemia AML-M5) and two deaths (one from hepatoblastoma, one from AML) occurred. The 10-years event free survival and overall survival probabilities were 95.5% (95% CI 91.9-99.1) and 98.7% (95% CI 96.8-100), respectively. Sixty-eight non-oncologic health-events included 57 cases of hearing loss (including 25 Brock 3-4), three liver cirrhosis, three pre-operative portal cavernoma, two focal nodular hyperplasia, two grade-1 chronic kidney diseases and one asymptomatic cardiac dysfunction were reported. Ototoxicity was significantly associated with cisplatin cumulative dose (OR = 2.07, 95% CI 1.32-3.24, p = 0.001) and carboplatin exposure (OR = 3.14, 95% CI 1.30-7.58, p = 0.01) in multivariable analysis adjusted for sex and age at diagnosis. CONCLUSIONS: With current risk-adapted strategies, hepatoblastoma is a highly curable disease, with very rare relapses, and few late effects except hearing loss which remains a serious condition in these very young patients.

Dental abnormalities and preventive oral care in Schimke immuno-osseous dysplasia.

BACKGROUND: Schimke immuno-osseous dysplasia (SIOD) is a rare, severe, autosomal recessive disorder that results in spondyloepiphyseal dysplasia, renal dysfunction, immunodeficiency, facial dysmorphism and growth failure. Little is known about oral features associated with SIOD. Some of the dental anomalies encountered are specific to SIOD and have only been reported in individuals with SIOD. CASE REPORT: This paper describes the clinical and radiographic dental manifestations of SIOD in two Caucasian brothers. Both lived to be about 10 years old. After a variety of symptoms were reported, a diagnosis of SIOD was finally made when the brothers were, respectively, 5 and 8 years old. At that time, dental anomalies, such as dyschromia, bulbous crowns, short and thin roots, had not been taken into account to establish the diagnosis. However, knowledge of the dental features characteristic of this disease could have helped make the diagnosis. Although both were caries- and periodontal disease-free, special attention was focused on prevention, including dietary counselling, plaque control, oral hygiene instructions and the use of fluoridated toothpaste. FOLLOW-UP: The two patients were followed every 6 months, for over 2 years (until their death), by both a private dentist and a university hospital dentist, which helped them maintain good oral health. Oral hygiene was assessed at each appointment and fissure sealants were placed by the private practitioner on their first permanent molars. CONCLUSION: This report describes dental anomalies specific to SIOD that could facilitate diagnosis. Clinicians and dentists should work in collaboration to diagnose and treat children with SIOD. These patients require regular and specific dental management because of their fragile health and their characteristic dental anomalies. Ideally, preventive visits should be scheduled every 6 months in addition to curative visits as needed.

Dental abnormalities in Schimke immuno-osseous dysplasia.

Described for the first time in 1971, Schimke immuno-osseous dysplasia (SIOD) is an autosomal-recessive multisystem disorder that is caused by bi-allelic mutations of SMARCAL1, which encodes a DNA annealing helicase. To define better the dental anomalies of SIOD, we reviewed the records from SIOD patients with identified bi-allelic SMARCAL1 mutations, and we found that 66.0% had microdontia, hypodontia, or malformed deciduous and permanent molars. Immunohistochemical analyses showed expression of SMARCAL1 in all developing teeth, raising the possibility that the malformations are cell-autonomous consequences of SMARCAL1 deficiency. We also found that stimulation of cultured skin fibroblasts from SIOD patients with the tooth morphogens WNT3A, BMP4, and TGFß1 identified altered transcriptional responses, raising the hypothesis that the dental malformations arise in part from altered responses to developmental morphogens. To the best of our knowledge, this is the first systematic study of the dental anomalies associated with SIOD.

Diagnosis of fetal urinary tract malformations: prenatal management and postnatal outcome.

OBJECTIVE: To evaluate prenatal management and to define the criteria of gravity for accurate assessment of the renal and overall prognosis of fetuses presenting malformations of the urinary tract. METHODS: We carried out a retrospective study of 127 cases of urinary tract malformation. We carried out descriptive statistical and univariate analyses as a function of severity criteria and the outcome of pregnancy. RESULTS: One-third of fetuses presented associated extrarenal malformations and 10% of the karyotypes were abnormal. There were more abortions in case of decrease in amniotic fluid volume (p < 0.001), extent of renal damage (p < 0.05), presence of associated extrarenal malformations (p < 0.05), early diagnosis of the malformation (p < 0.001) and presence of chromosomal syndrome (p = 0.01). In our study, there was an excellent correlation between prenatal data and pathological findings for the fetus following abortions for medical reasons or obtained during the surveillance of live-born children. Fetal biochemistry made very little contribution. CONCLUSION: In cases of urinary tract malformation, this work confirms the need for regular and frequent ultrasound scans, checking for the echographic factors indicative of gravity and for adapted karyotyping. It also demonstrates that pluridisciplinary management is necessary for the prenatal evaluation of renal and overall fetal prognosis.

Antibiotic prophylaxis for the prevention of recurrent urinary tract infection in children with low grade vesicoureteral reflux: results from a prospective randomized study.

PURPOSE: Antibiotic prophylaxis is given to children at risk for urinary tract infection. However, evidence concerning its effectiveness in grade I to III vesicoureteral reflux is lacking. The objective of this study was to determine whether antibiotic prophylaxis reduces the incidence of urinary tract infection in young children with low grade vesicoureteral reflux. MATERIALS AND METHODS: Children 1 month to 3 years old with grade I to III vesicoureteral reflux were assigned randomly to receive daily cotrimoxazole or no treatment, and followed for 18 months. A urinary tract infection constituted an exit criterion. Infection-free survival rates were calculated using the Kaplan-Meier method and compared using the log rank test. RESULTS: A total of 225 children were enrolled in the study. Distribution of gender, age at inclusion and reflux grade were similar between the 2 groups. There was no significant difference in the occurrence of urinary tract infection between the 2 groups (17% vs 26%, p = 0.2). However, a significant association was found between treatment and patient gender (p = 0.017). Prophylaxis significantly reduced urinary tract infection in boys (p = 0.013), most notably in boys with grade III vesicoureteral reflux (p = 0.042). CONCLUSIONS: These data suggest that antibiotic prophylaxis does not reduce the overall incidence of urinary tract infection in children with low grade vesicoureteral reflux. However, such a strategy may prevent further urinary tract infection in boys with grade III reflux.

Prader-Willi syndrome and polygonosomal abnormalities in males:about a Prader-Willi/47,XYY patient.

We herein report a male patient known as having a XYY karyotype. At the age of 26 years a Prader-Willi syndrome (PWS) was diagnosed. Before that time the whole symptomatology was ascribed to the XYY syndrome. This is the first reported association of PWS and polygonosomal abnormality in a male adult (whose height is above average).

[Glomerular nephropathy with IgA mesangium deposits and Crohn disease]. / Néphropathie glomérulaire à dépôts mésangiaux d'IgA et maladie de Crohn.

BACKGROUND: Renal disease is an unfrequent extraintestinal manifestation of chronic inflammatory bowel disease. CASE REPORT: A 12-year-old girl suffered from recurrent abdominal pain, diarrhea and growth impairment due to Crohn's disease of ileocaecal region. After six months of nutritional rehabilitation, an ileo-caecal resection was performed because of intestinal stenosis. The surgical procedure was followed by parietal abcess and cutaneous fistula. One year later, a purulent secretion came out of the fistula associated with fever, hematuria and acute renal failure. Renal biopsy confirmed IgA nephropathy. The course was favorable under parenteral nutrition and after surgical closure of the sigmoido-cutaneous fistula. The microscopic hematuria only persisted but the nephropathy did not relapse even during a further digestive exacerbation. CONCLUSION: IgA nephropathy has been reported in association with chronic inflammatory bowel disease. Its mechanism remains unclear: increased mucosal IgA production in inflammatory bowel, increased serum IgA and/or immune complex deposition in the renal mesangium appear the most relevant hypotheses.