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Neuroblastoma is the most common pediatric extracranial solid cancer. Patients with metastatic disease at initial diagnosis who are greater than 18  months of age and patients with MycN amplified locoregional tumors are treated with intensive multimodal therapy. While this intensive approach has been shown to improve outcome, patients with high-risk disease frequently relapse and fewer than 50% of these patients will be long-term survivors necessitating new approaches for therapy. Derived from the sympathetic nervous system, this tumor typically expresses the norepinephrine transporter. This transporter mediates active intracellular uptake of metaiodobenzylguanidine (MIBG) an analogue of norepinephrine in approximately 90% of patients allowing the use of radiolabeled (metaiodobenzylguanidine) MIBG, for targeted radiotherapy. This article will review the clinical experience of using MIBG as targeted radiotherapy in neuroblastoma. The administration guidelines, toxicity, response and survival are discussed. Recent studies have evaluated combinations of (131)I-MIBG with myeloablative regimens such as chemotherapy agents with radiation sensitizing properties, or with biologic agents. Most of them report a response rate of 30-40% with (131)I-MIBG in patients with relapsed or refractory neuroblastoma. Due to this high response rates and low non-hematologic toxicity, (131)I-MIBG seems to be an interesting agent for incorporation into the upfront management of newly diagnosed patients with high-risk neuroblastoma.

Pheochromocytoma and neuroblastoma are distinct tumours, but their biological diagnosis is based on secretion increase of one or several catecholamines. Assays have to be very sensible and specific for an early diagnosis. 24 hours urinary catecholamines and metabolites are currently measured, but technical improvements permit plasma metanephrine assay, an excellent indicator of pheochromocytoma. HPLC coupled to electrochemical detection represents the most efficient methodology. After a review of urinary and plasma assay methods, the authors show usual values of catecholamines, metanephrines, HVA and VMA, according to ages, and give examples of results encountered in classical or not tumours and in falsely positive cases. Urinary metanephrine assay is the most sensible and specific in biological diagnosis of pheochromocytoma, while catecholamines and VMA assays lack of sensibility. Results have to be given by 24 hours and by creatinine ratio. Metanephrine assay can be performed also in plasma and exhibits the same interest. However, in urine as in plasma, in case of renal failure, results cannot be interpreted. Neuroblastoma biological diagnosis is based classically on HVA, VMA, and dopamine assays, nowadays only in 24 hours urine (or in urinary micturition for screening), and results are also expressed as creatinine ratio. But even if several assays are advisable, 5% of the neuroblastoma cases do not produce increased catecholamine values. In some cases, metanephrine assay could be of interest. After the age of 12 months, clinical expression of neuroblastoma is dramatic in 70% of cases. So, a biological screening has been experimented in several countries including France. A French translation of the consensus conference report (1998) is appended, which shows the complexity of neuroblastoma screening. Now, there is no evidence that early tumour detection by screening lessens the mortality rate, but a weak benefit is not excluded.

Background: Cardiovascular disorders associated with neural crest tumors are congenital malformations rather than cardiomyopathies., Case Report: A 18 month-old girl developed heart failure one week after discovery of an adrenal neuroblastoma with excessive secretion of catecholamines. Investigation showed dilated cardiomyopathy without myocardial hypertrophy. Besides chemotherapy, the patient was given nitrous derivatives, diuretics and converting enzyme inhibitor. His cardiac condition gradually improved so that partial resection of the tumor was possible 2 years later., Conclusions: The cardiomyopathy presented by this patient is possibly catecholamine-induced even though catecholamines usually results in myocardial hypertrophy rather than dilated cardiomyopathy. The reason why such a cardiomyopathy has never been reported in patients with neuroblastoma remains unclear.

A retrospective comparison of urinary excretion of norepinephrine, epinephrine, dopamine and/or their acidic metabolites, HVA and VMA, in 36 children with neuroblastoma versus 360 hospitalized children without neuroblastoma showed a sensibility of 72% and a specificity of 98% for HVA and 80% and 97% for VMA respectively. Consequently, the sensibilities and specificities of these 2 determinations confirm their useful purpose for the biochemical diagnosis of neuroblastoma in preference to the determinations of norepinephrine, epinephrine and dopamine.

The case of a 16 month old infant presenting with an abdominal tumour and systemic hypertension is reported. The profile of urinary plasma and tumour catecholamine levels corresponded with that of a pheochromocitoma. The combination of alphablockers and betablockers was the only effective treatment of the peaks of preoperative hypetension. The tumour was completely excised and was found to be a ganglioneuroblastoma. No recurrence has been observed after 3 years post-operative follow-up. The incidence and mechanisms of hypertension in neuroblastoma are reviewed. Only these histological forms of ganglioblastoma have the enzymatic set up for the synthesis and release of pressor amines.

As suggested by Hakomori, one of the mechanisms to explain the abnormal proliferation of tumor cells by loss of contact inhibition could be a modification of membrane gangliosides. We report here a case of neuroblastoma with opsomyoclonia in which the ganglioside profile is abnormal, with a high level of GP3 and GM2, and of other gangliosides which are not present in normal child and adult brains.

The radioreceptor assay for acetylcholine (ACh) is based on the ability of the ACh to compete with the specific binding of [3H] cis-methyldioxolane to muscarinic receptors of rat cerebral cortex membranes. The technique described was used to measure ACh levels in NS 20 cells treated with an organophosphorus compound. The down regulation of muscarinic acetylcholine receptors of neuroblastoma cells observed is probably related to ACh accumulation.

A 18-month-old boy with stage 4 neuroblastoma needed intensive care because of prerenal acute renal failure related to an intractable watery diarrhoea syndrome occurring 10 months after the diagnosis of the primary tumor. This diarrhoea was in relation with a late hyperproduction of vasoactive intestinal peptide by the relapsing neuroblastoma itself and stopped with intravenous somatostatin administration.

An apparently anaplastic retroperitoneal tumour was studied by a cell culture method, The patient was a young man. The method used revealed the morphological features and secretory potential of the lesion, which could thus be diagnosed as an immature neuroblastoma.

Urinary 3-O methyldopamine has been found highly increased in all cases of malignant tumours, as well of sympathetic nature (sympathoblastoma) as of chromaffin type (pheochromocytoma) but at a lesser extent in benign sympathetic tumours (ganglioneuroma). On the other hand, 3-O methyldopamine excretion is normal in benign pheochromocytoma. The ratio of this compound in the dopaminergic block is increased in sympathoblastoma, decreased in ganglioneurona and unchanged in pheochromocytoma. This kind of analysis has not been made for the case of malignant pheochromoblastoma. This ratio of 3-O methyldopamine in the whole dopaminergic and noradrenergic metabolism is increased only in sympathoblastoma. In the other cases (ganglioneuroma and pheochromocytoma) this ratio is decreased. Comparative analysis of urinary 3-O methyldopamine and the two other methoxylated amines (norepinephrine and metanephrine) shows that the methoxylated derivative of dopamine, when compared to normal subjects values, increased at the greatest extent in sympathoblastoma, while in ganglioneurona and chromaffin tumours, normetanephrine is with a variable degree, the predominant compound.