Unusual association of non-anaplastic Wilms tumor and Cornelia de Lange syndrome: case report

Background: Cornelia de Lange syndrome is the prototype for cohesinopathy disorders, which are characterized by defects in chromosome segregation. Kidney malformations, including nephrogenic rests, are common in Cornelia de Lange syndrome. Only one post-mortem case report has described an association between Wilms tumor and Cornelia de Lange syndrome. Here, we describe the first case of a living child with both diseases. Case presentation: Non-anaplastic triphasic nephroblastoma was diagnosed in a patient carrying a not yet reported mutation in NIPBL (c.4920 G > A). The patient had the typical facial appearance and intellectual disability associated with Cornelia de Lange syndrome in absence of limb involvement. The child's kidneys were examined by ultrasound at 2 years of age to exclude kidney abnormalities associated with the syndrome. She underwent pre-operative chemotherapy and nephrectomy. Seven months later she was healthy and without residual detectable disease. Conclusion: The previous report of such co-occurrence, together with our report and previous reports of nephrogenic rests, led us to wonder if there may be any causal relationship between these two rare entities. The wingless/integrated (Wnt) pathway, which is implicated in kidney development, is constitutively activated in approximately 15-20 % of all non-anaplastic Wilms tumors. Interestingly, the Wnt pathway was recently found to be perturbed in a zebrafish model of Cornelia de Lange syndrome. Mutations in cohesin complex genes and regulators have also been identified in several types of cancers. On the other hand, there is no clear evidence of an increased risk of cancer in Cornelia de Lange syndrome, and no other similar cases have been published since the fist one reported by Cohen, and this prompts to think Wilms tumor and Cornelia de Lange syndrome occurred together in our patient by chance

Évaluation de la gastrostomie précoce dans la prise en charge des tumeurs osseuses primitives malignes de l’enfant. Expérience du groupe Grand Ouest Cancer de l’Enfant (GOCE) sur 10 ans [Assessment of early gastrostomy in the treatment of primary malignant bone tumors in children. A report from the French children's oncology study Group GOCE]

International audiencePurpose. - Patients in pediatric oncology are at high risk of undernourishment, especially during intensive treatment such as malignant primary bone tumors. Many consequences of malnutrition have been highlighted, yet the nutritional care is not standardized. We evaluated the nutritional benefits and the feasibility of enteral nutrition on early gastrostomy, by comparison to other methods of nutritional support during the treatment of malignant primary bone tumor in children. Methods. - The characteristics of patients with malignant primary bone tumors have been retrospectively analyzed in Western regions of France from 2003 to 2013. The census of complications of early gastrostomy and the nutritional parameters of patients (Z-scores weight for height and height for age and body mass index) allowed the evaluation of its feasibility and effectiveness. Complications data, nutritional status and oncology treatment were also analyzed in the groups of patients who received enteral nutrition through nasogastric tube and those who did not receive it. Results. - Early gastrostomy was inserted in 58 patients, a nasogastric tube in 20 and 60 did not receive any of these two nutritional supports. Early gastrostomy is a purveyor of complications (82 for 58 patients) but they are minor and not specific (92.7%). No difference between the three groups has been demonstrated about the frequency of complications, the number of hospitalization or their duration. Early gastrostomy avoided a deterioration of the nutritional status as soon as the preoperative stage unlike the two other groups. No significant difference in survival at 4 years was found between the three groups. Conclusion. - Early gastrostomy is an effective nutritional support which does not increase complications and which does not affect the oncologic prognosis. Its psychological evaluation and nutritional impact in the long term are to be assessed on a prospective group. (C) 2017 Elsevier Masson SAS. All rights reserved

Zoledronic Acid as a New Adjuvant Therapeutic Strategy for Ewing's Sarcoma Patients

International audienceEwing's sarcoma (ES) is the second most frequent pediatric bone tumor also arising in soft tissues (15% of cases). The prognosis of patients with clinically detectable metastases at diagnosis, not responding to therapy or with disease relapse, is still very poor. Among new therapeutic approaches, bisphosphonates represent promising adjuvant molecules to chemotherapy to limit the osteolytic component of bone tumors and to protect from bone metastases. The combined effects of zoledronic acid and mafosfamide were investigated on cell proliferation, viability, apoptosis, and cell cycle distribution of human ES cell lines differing in their p53 and p16/ink4 status. ES models were developed to reproduce both soft tissue and intraosseous tumor development. Mice were treated with 100 μg/kg zoledronic acid (two or four times per week) and/or ifosfamide (30 mg/kg, one to three cycles of three injections). ES cell lines showed different sensitivities to zoledronic acid and mafosfamide at the cell proliferation level, with no correlation with their molecular status. Both drugs induced cell cycle arrest, but in the S or G2M phase, respectively. In vivo, zoledronic acid had no effect on soft tissue tumor progression, although it dramatically inhibited ES development in bone. When combined with ifosfamide, zoledronic acid exerted synergistic effects in the soft tissue model: Its combination with one cycle of ifosfamide resulted in an inhibitory effect similar to three cycles of ifosfamide alone. This very promising result could allow clinicians to diminish the doses of chemotherapy. Cancer Res; 70(19); 7610–9. ©2010 AACR