[Chronic aqueous diarrhea in children: An unusual etiology]. / Diarrhée aqueuse chronique chez l'enfant : une étiologie à ne pas méconnaître.

Peripheral neuroblastic tumors are the most common extracranial solid tumors in children. On the other hand, diarrheal neuroblastic tumors are quite rare and not easy to diagnose in the early stage. We report a case of neuroblastic tumor in a 2-year old girl presenting with aqueous diarrhea caused by paraneoplasic secretion of VIP.

The mitochondrial apoptotic pathway is induced by Cu(II) antineoplastic compounds (Casiopeínas®) in SK-N-SH neuroblastoma cells after short exposure times.

The family of Copper(II) coordination compounds Casiopeínas® (Cas) has shown antiproliferative activity in several tumour lines by oxidative cellular damage and mitochondrial dysfunction that lead to cell death through apoptotic pathways. The goal of this work is looking for the functional mechanism of CasIIgly, CasIIIia and CasIIIEa in neuroblastoma metastatic cell line SK-N-SH, a paediatric extra-cranial tumour which is refractory to several anti-carcinogenic agents. All Cas have shown higher antiproliferative activity than cisplatin (IC50 = 123 µM) with IC50 values of 18, 22 and 63 µM for CasIIgly, CasIIIEa and CasIIIia, respectively. At low concentrations and early times (4 h), these compounds cause a disruption of the mitochondrial transmembrane potential (Δψm). Concomitantly, an important depletion of intracellular glutathione and an increase of reactive oxygen species (ROS) hydrogen peroxide and radical superoxide were observed. On the other side, the lower cytotoxic effect of Casiopeínas on cultures of human peripheral blood lymphocytes (IC50CasIIgly  = 1720 µM, IC50 CasIIIEa  = 3860 µM and IC50 CasIIIia  = 4700 µM) show the selectivity of these compounds over the tumour cells compared with the non-transformed cells. Chemically, glutathione (GSH) interacts with Casiopeínas® through the coordination of sulphur atom to the metal centre, process which facilitates the electron transfer to get Cu(I), GSSG and the posterior production of ROS. Additionally, the molecular structure of CasIIIia as nitrate is reported. These results have shown that the anticarcinogenic activity of Casiopeínas® on neuroblastoma SK-N-SH is through mitochondrial apoptosis due to the enhanced pro-oxidant environment promoted by the presence of the coordination copper compounds.

Survival impact of postoperative radiotherapy in patients with olfactory neuroblastoma: 513 cases from the SEER database.

PUPOSE: To evaluate the impact of postoperative radiotherapy (PORT) on survival in olfactory neuroblastoma (ONB) patients with different tumor staging. MATERIAL AND METHODS: Patients with ONB were selected in the Surveillance, Epidemiology and End Results (SEER) database from 2004-2016. Survival analyses were performed using Kaplan-Meier (K-M) method, Cox regression analysis, and competing risk model. RESULTS: A total of 513 patients were included in the study. Univariate and multivariate analysis results demonstrated that PORT was not an independent prognostic factor for overall survival (OS) of modified Kadish stage A and B patients (P=0.699 and P=0.248, respectively). Kadish stage C and D patients who underwent PORT had significantly better OS than those who did not undergo PORT (P=0.03 and P<0.0001). K-M curves revealed that the 5- and 10-year OS rates of patients who underwent PORT vs. non-PORT were 85.3% vs. 70.4% and 68.2% vs. 56.8% in stage C patients, respectively. For stage D patients, the 5-year OS rates were 70.7% and 42.6%, and 10-year OS rates were 53.4% and 29.5% in the PORT and non-PORT groups, respectively. The competitive risk model revealed that the 5-year cancer-specific cumulative mortality incidence decreased by 26.6% while the 10-year mortality incidence decreased by 41.4% in Kadish stage C patients who were treated using PORT; meanwhile, for Kadish stage D patients who were treated with PORT, the 5- and 10-year mortality incidences were reduced by 35.3% and 42.6%, respectively. Furthermore, we found that chemotherapy was not related to the prognosis of ONB patients (all P>0.05). CONCLUSION: Our results indicate that PORT improved survival outcomes of modified Kadish stage C and D ONB patients. However, PORT may not affect survival for modified Kadish stage A and B individuals. Chemotherapy was not recommended for ONB; therefore, further studies are warranted to determine its therapeutic significance.

Guide for paediatric radiotherapy procedures.

A third of children with cancer receive radiotherapy as part of their initial treatment, which represents 800 paediatric irradiations per year in France carried out in 15 specialized centres approved on the recommendations of the French national cancer institute in decreasing order of frequency, the types of cancer that require irradiation are: brain tumours, neuroblastomas, Ewing's sarcomas, Hodgkin's lymphomas, soft tissue sarcomas including rhabdomyosarcomas, and nephroblastomas. The treatment guidelines follow the recommendations of the French society for childhood cancers (SFCE) or the French and European prospective protocols. The therapeutic indications, the technical and/and ballistic choices of complex cases are frequently discussed during bimonthly paediatric radiotherapy technical web-conferences. All cancers combined, overall survival being 80%, long-term toxicity logically becomes an important concern, making the preparation of treatments complex. The irradiation methods include all the techniques currently available: 3D conformational irradiation, intensity modulation radiation therapy, irradiation under normal or hypofractionated stereotaxic conditions, brachytherapy and proton therapy. We present the update of the recommendations of the French society for radiation oncology on the indications, the technical methods of realization and the organisation and the specificities of paediatric radiation oncology.

[High-risk neuroblastoma treatment strategy: The experience of the SIOPEN group]. / Prise en charge des neuroblastomes de haut risque : l'expérience du groupe européen SIOPEN.

High-risk neuroblastoma comprises nearly half of cases of neuroblastoma and the long-term survival is less than 50% despite complex and intensive treatments. Studies conducted in Europe and in North America in the last two decades have identified a strategy based on four therapeutic phases: an intensive induction therapy, a local control by surgery and radiation, a consolidation phase with single or tandem high dose chemotherapy and autologous transplant, and immunotherapy to eliminate residual disease. Future treatment improvements are based on progress at each of these therapeutic steps and ultimately a better stratification of the strategy adapted to the type of risk. A more extensive tumor molecular profiling at diagnosis and relapse will help to develop new therapeutics and to guide risk-based strategies. Earlier use of immunotherapy and identification of more effective combinations in induction or in maintenance treatment, identification of indications of more intense consolidations using high-dose chemotherapy combined or not with metabolic irradiation by 131I-MIBG and the introduction of other targeted treatments are tracks being explored.

Protection by polyphenol extract from olive stones against apoptosis produced by oxidative stress in human neuroblastoma cells

OBJECTIVE: We evaluated the protective activity of an extract from a by-product such as olive stones, through its ability to inhibit H202 induced apoptosis in the SH-SY5Y human neuroblastoma cell line. MATERIAL AND METHODS: To such end, 20,000 cells/well were cultivated and differentiation with retinoic acid was initiated. Once the cells were differentiated, apoptosis was induced with and without H2O2 extract. Finally, cDNA extraction was performed, and pro-apoptotic genes Bax and anti-apoptotic genes Bcl-2 were analyzed. Quantification of the gene expression was performed using the GAPDH gene marker. RESULTS: Cell viability with the extract is 97.6% (SD 5.7) with 10 mg/l and 62.8% (SD 1.2) to 50 mg/l, using 10 mg/l for the biomarker assay. The retinoic acid differentiated SH-S cell line (10 µM) shows a clear apoptosis when treated with H2O2 150 µM, with a Bax/Bcl-2 ratio of 3.75 (SD 0.80) in contrast to the differentiated control cells subjected to H2O2 and with extract, which have the same ratio of 1.02 (SD 0.01-0.03). CONCLUSION: The olive stone extract shows anti-apoptotic activity in the provoked cell death of SH-SY5Y human neuroblastoma cells in their normal state, defending them from oxidative stress which produces a significant increase in the apoptotic gene ratio in contrast to anti-apoptotic genes (Bax/Bcl-2).

[Mediastinal neuroblastoma: Unusual localization with late revelation]. / Neuroblastome médiastinal : localisation inhabituelle à révélation tardive.

Neuroblastoma (NB) is an embryonal tumor of the sympathetic nervous system. It represents the most common malignant extracerebral solid tumor, and the first solid tumor in children aged less than one year. Neuroblastoma is rare in adults. We report the case of a 21-year-old male patient. Diagnosis of neuroblastoma was confirmed by percutanous CT scanner biopsy. Radiological assessment of the extension concluded to a stage IV NB with multifocal bone disease. The patient received chemotherapy based on cisplatin-etoposide (6 cycles) and a mediastinal radiotherapy. The evolution was marked by the progression of bone metastasis and the emergence of a tissular process sheathing the left optic nerve and the terminal portion of the internal carotid artery. Second line chemotherapy was indicated. A thoracic localization of NB is rare. Treatment is not codified and the prognosis is variable.

[Neurogenic mediastinal tumors in adults]. / Tumeurs neurogènes du médiastin de l'adulte.

INTRODUCTION: Neurogenic mediastinal tumors are tumors develop at the expense of peripheral nerve elements of the mediastinum, the sympathetic nervous tissue and paraganglia. The series that we propose has the distinction of a high frequency of malignant forms and a wealth of clinical symptomatology. METHODS: This is a retrospective study of 9 patients collected over a period of 6 years. The epidemiological aspect, clinical, radiological, surgical treatment and his results, histological diagnosis and prognosis were reviewed. RESULTS: Five women and 4 men were identified. All patients were symptomatic at diagnosis. Tumor resection was complete in 8 cases. In 3 patients, there was a malignant tumor. Two of them had received chemo-radiotherapy. The others showed good clinical progress with a mean of 35 months. CONCLUSION: Neurogenic tumors in adults are usually discovered incidentally. When the malignant forms predominate or in the presence of large tumor, the symptoms can be quite marked. In all cases the treatment based on a complete surgical resection remains the only guarantee of a good prognosis.

[Radiotherapy for paediatric cancers]. / Radiothérapie des cancers de l'enfant.

The purpose of this article is to describe the specificities of paediatric radiation oncology: cancer types, radiotherapy indications, techniques, organisation and reglementary framework.

[Neonatal neuroblastoma complicated with a threatening tumoral hepatomegaly treated by irradiation: No sequel 20 years later]. / Neuroblastome néonatal, compliqué d'une hépatomégalie tumorale menaçante, traité par irradiation : absence de séquelle 20ans après.

In this article, we report the case of a newborn who presented a life-threatening hepatomegaly with respiratory distress at 12 days of life, complicating a metastatic neuroblastoma. Low-dose liver radiotherapy was performed in emergency in order to decompress. Chemotherapy has also been delivered due to a tumoral relapse 1 month after radiotherapy. After a follow-up of 20 years, this young woman is still in complete remission, with no long-term sequelae.

Prenatally Diagnosed Cystic Neuroblastoma: A Case Report

Cystic masses of the adrenal gland are unusual in the fetus and most are secondary to hemorrhage. Cysticneuroblastoma is extremely rare, and in contrast to solid neuroblastoma, follows a benign course, is diagnosedearlier, and rarely presents with metastatic lesions(1-4). We report one case of cystic neuroblastoma diagnosedprenatally by ultrasound(US) and magnetic resonance(MR) imaging, and include a review of the literature.