Natural course of neuroblastoma detected by mass screening: s 5-year prospective study at a single institution.

PURPOSE: To describe various favorable courses of neuroblastoma (NBL) detected by mass screening and to present our observation program as a temporary treatment option, to be used until a final decision is made regarding the mass screening program for 6-month-old infants. PATIENTS AND METHODS: Between October 1993 and November 1999, 26 of 51 patients with NBL detected by mass screening were enrolled in our observation program. The criteria for observation included urinary vanillylmandelic acid (VMA) and homovanillic acid (HVA) levels less than 50 microg/mg creatinine, smaller tumor size (< 5.0 cm), preoperative status, and granted informed consent. Patients were divided into four groups according to changes in urinary VMA and HVA values and tumor size. Patients who no longer fulfilled criteria underwent surgery. RESULTS: The observation period ranged from 4 to 73 months. Urinary VMA and HVA levels decreased in 19 of 26 patients, often by age 16 months. Eighteen patients had regressing tumors, and in 10 of these cases, the tumor was undetectable or barely detectable by imaging techniques. Four patients younger than 12 months had increased tumor marker levels and tumor volume, histologically reflecting neuroblastic proliferation. The remaining three patients, all older than 18 months, had varied tumor marker levels but increased tumor volume, histologically reflecting an increase in Schwann cells. No upgrading of tumor stage or unfavorable biologic factor was noted in any patient. CONCLUSION: None of our patients showed evidence of transition from favorable to unfavorable prognosis, a finding that points to a reduction in the significance of screening as a public health measure. Until results of ongoing screening trials involving older patients have been evaluated, the observation program can be used as a temporary measure to avoid, with little risk, unnecessary surgical intervention.

[Congenital cyanotic heart disease and peripheral neurogenic tumor]. / Cardiopatía cianótica congénita y tumor neurógeno periférico.

The association between neuroblastic tumours and congenital heart disease is widely confirmed in the literature references. The authors describe a case of a patient with congenital heart disease, high blood pressure, renal artery stenosis and high levels in 24 hours urine metanephrines. A MIBG-I-123 scintigraphy was essential for the diagnosis of neuroblastic tumour.

Long-term outcome in children with opsoclonus-myoclonus and ataxia and coincident neuroblastoma.

We reviewed the neurologic and developmental courses in 10 children with opsoclonus-myoclonus ("dancing eyes syndrome") and neuroblastoma. All patients are alive without evidence of neoplastic disease after 8+ to 111+ months of follow-up. All had localized disease and 50% had extraabdominal tumors. Neuroblastomas of nine children had favorable Shimada histologic characteristics, and all tumors had single copies of the N-myc oncogene. After neuroblastoma resection, all patients had persistent opsoclonus-myoclonus or ataxia that responded to therapy with adrenocorticotropic hormone. Nine children had relapses of neurologic symptoms. Three years after resection, six of seven patients with sufficient follow-up were free of symptoms and had discontinued therapy. However, nine children had chronic neurologic deficits, including cognitive and motor delays, language deficits, and behavioral abnormalities. All six patients in educational programs required special assistance. Five children required physical, occupational, or speech therapy. Long-term developmental and cognitive problems should be anticipated in patients with neuroblastoma who have opsoclonus-myoclonus or ataxia or both, and early intervention should be instituted to try to minimize these deficits.

Urinary dopamine/noradrenaline and dopamine/vanillylmandelic acid ratios as a reflection of different biology of adrenergic clones in children's neuroblastic tumors.

The results of calculations of urinary dopamine/noradrenaline (DA/NAd) and dopamine/vanillylmandelic acid (DA/VMA) ratios in 54 untreated children with neuroblastic tumors are reported. Thirteen patients were in the prognostically favorable group (stages I, II, and IV-S and ganglioneuroma [GN]), and 41 had advanced neuroblastoma (stage III and IV). Among patients with ganglioneuroma and favorable neuroblastoma (n = 13), of whom all were survivors, the urinary DA/NAd and DA/VMA ratios exceeded 1.8 in only 2 cases of stage IV-S and stage I, respectively. In the advanced neuroblastoma group, the DA/NAd and DA/VMA ratios exhibited a wide range of values, but among the stage III and IV survivors (n = 10), DA/NAd ratios greater than 1.8 were noted in only 3 patients. The DA/VMA ratio was not greater than 1.8 in those 3 patients. The mean DA/NAd and DA/VMA proportions in the population comprising all survivors were 1.8 +/- 2.7 (mean +/- SD) and 1.1 +/- 0.4, respectively. The same computations carried out in patients who died showed higher values, ie, the mean DA/NAd and DA/VMA ratios were 5.2 +/- 6.3 and 5.6 +/- 10.5, respectively, showing the difference in DA/NAd and DA/VMA ratios between prognostically favorable and unfavorable groups. Of 23 survivors, only 4 had DA/NAd ratios greater than 1.8 (17%), while 24 of 31 children who died (77%) had DA/NAd ratios was greater than 1.8. The reported results suggest dissimilarity in the catecholamine metabolism of adrenergic clones with respect to the stage of advancement of neoplastic disease.

Mass screening for neuroblastoma in Japan.

The present status of the neuroblastoma mass screening program in Japan, the first national trial in the world, is evaluated. This program, now in its fifth year, was conducted in cooperation with the infants' mothers, local health centers, screening centers, and selected hospitals. From the onset of the program in Kyoto in 1973 to the end of 1989, 337 cases were detected and analyzed. Most cases were detected at early stages and 97% are expected to be cured. Several social, technical, and clinical problems remain unresolved.

Disparate urinary catecholamine patterns in secondary hypertension due to unique sequential development of pheochromocytoma and neuroblastoma.

A 43-year-old white woman had a pheochromocytoma removed from her left adrenal gland, and one year later she developed a new left upper abdominal mass that was found to be a neuroblastoma. On both occasions, urinary vanillylmandelic acid level was elevated. However, urinary norepinephrine and epinephrine levels were increased only during the pheochromocytoma episode, while the urinary homovanillic acid level was elevated only when neuroblastoma developed. Despite a high suspicion of pheochromocytoma recurrence, the urinary catecholamine profile was suggestive of neuroblastoma, which was revealed by histopathologic analysis of the tumor tissue.

Neuroblastoma. Mass screening for early detection and its prognosis.

Since July 1973, the authors began developing a mass screening system using a VMA (vanilmandelic acid) spot test on 6-to-7 month-old infants for early detection of neuroblastoma in Kyoto city, Japan. Using this method, six infants with this tumor were discovered; five of the six infants were cured, and one is under treatment. These patients showed a favorable prognosis on early diagnosis. In this article, 57 neuroblastoma patients from the Department of Pediatrics, Kyoto Prefectural University of Medicine, treated during the last 20 years, from July 1962 to June 1982, are evaluated. Since the mass screening program has run smoothly since July 1974, clinical findings are compared between 35 neuroblastoma cases before mass screening from the 12-year period from July 1962 to June 1974 and 22 cases after mass screening, during the 8-year period from July 1974 to June 1982. Before mass screening, only 20% (7/35) of the patients were discovered with neuroblastoma younger than 12 months of age and 68.6% were older than 2 years of age. After mass screening, 54.6% (12/22) of the patients were younger than 12 months of age and only 31.8% (7/22) were older than 2 years of age. Before mass screening, 17.1% (6/35) survived with five of the six surviving patients being younger than 12 months of age at the time of diagnosis; 72.7% (16/22) of the patients detected after mass screening are living now. Eleven of the 16 patients have already been cured, and the remaining 5 patients are presently undergoing treatment. A marked improvement of their prognoses is dependent on the early detection of this tumor by mass screening. To date, using the VMA spot test for early detection in infancy is convenient and effective for improvement of its prognosis.

Calcification and uptake of Tc-99m diphosphonates in neuroblastomas: concise communication.

Sixty-six percent of 54 patients with neuroblastoma demonstrated uptake of bone-seeking radioagents by the primary tumor. This is a higher incidence than previously reported. Uptake was slightly more common in abdominal than thoracic tumors. There was a significant correlation between the size of the tumor and tracer uptake. Calcification was demonstrated in the primary tumor in almost 90% of the 54 patients. This is a much higher incidence of calcification than previously reported. Microscopy shows that the calcification is not always due to tumor necrosis; it also occurs in areas of viable tumor cells. Tracer uptake is believed to be related to calcium metabolism. The rate of metabolic activity rather than the total amount of calcium present within the tumor may be the most important factor in determining the amount of uptake. No significant relationship was found between tracer uptake and tumor stage or homovanillic acid and vanillylmandelic acid metabolic activity.

[Abdominal sympathoma in adults. Apropos of 3 cases, with review of the literature]. / Le sympathome abdominal de l'adulte. A propos de trois cas, avec revue de la littérature.

Three cases of abdominal sympathoma, a tumor generally affecting young children, presented with clinical symptomatology differing from that observed in infants. Diagnosis is much more difficult and the prognosis constantly fatal.

[Infantile myoclonic encephalopathy with opsoclonus and neuroblastoma. Apropos of 2 cases]. / Encefalopatía mioclónica infantil con opsoclonus y neuroblastoma. A propósito de dos observaciones.

Two cases of infantile myoclonic encephalopathy with opsoclonus and neuroblastoma are reported. One of them was observed in a 16-month-old boy and the remaining one in a 13-month-old girl. In both cases the tumour was a stade III abdominal neuroblastoma. Urinary catecolamine excretion was increased in the girl and that of VMA in both patients. Treatment of the tumour with surgery, radiotherapy and chemotherapy resulted in a immediate disappearance of the neurologic picture in the girl. The same measures were equally successful in the boy implemented with a course of ACTH. Both children are free of tumour three years later, and they do not bear any psychomotor sequelae. The main features of this rare association are briefly commented.

Severe hypertension in a child with ganglioneuroblastoma.

A 26-month-old boy with Stage III abdominal ganglioneuroblastoma had tachycardia and hypertension. The hypertension increased following the institution of chemotherapy and necessitated the use of both alpha and beta adrenergic blocking agents to control the effects of the marked catecholamine production. After excision of the residual tumor, the blood pressure and urinary catecholamine excretion returned to normal. Histologic examination of this tissue under light microscopy revealed some sections of ganglioneuroblastoma as well as large areas of ganglioneuroma. Examination by electron microscopy demonstrated a moderate number of dense core neurosecretory-type granules in the cell bodies of the ganglion-like cells and an abundance of the same type of granules in the bundles of the interwoven cytoplasmic neural processes. To data, 32 months after diagnosis and 20 months off chemotherapy, the patient remains free of tumor and is in excellent general health. We postulate that the large number of secretory granules in this tumor permitted storage and release of markedly increased quantities of norepinephrine and resulted in a clinical profile similar to that associated with pheochromocytoma.

Control of fever associated with visceral cancers by indomethacin.

Fever commonly complicates intra-abdominal cancer when there are peritoneal or liver metastases but no infection. Although aspirin and acetaminophen have little or no effect on this fever and its debilitating effects, we have found that indomethacin dramatically and completely eliminates the fever. This observation and the measured decrease in urinary excretion of prostaglandin E2 suggest that fever associated with visceral tumors may be mediated by prostaglandins.

Ultrastructural studies on neuroblastoma: evaluation of cytodifferentiation and correlation of morphology and biochemical and survival data.

Fifteen cases of neuroblastoma, ganglioneuroblastoma and ganglioneuroma were studied by electron microscopy. Ultrastructural features of cytodifferentiation, including numbers of dense core neurosecretory granules (NSG) and neuritic processes, were used to evaluate variation within the neuroblastoma group to determine whether differences in cytodifferentiation exist where light microscopic variations are not evident. These studies revealed that undifferentiated neuroblastomas do show ultrastructural variations not evident by light microscopy. The ultrastructural findings for each case were compared with initial urinary catecholamine excretory patterns, the latter having recently been shown to have valuable prognostic significance. There was a positive correlation, in the undifferentiated neuroblastomas, between increased numbers of NSG and prognostically favorable biochemical excretory patterns. Conversely, low numbers of NSG were associated with an unfavorable biochemical pattern and fatal clinical course. These correlations between ultrastructural differentiation and the biochemical secretory pattern indicate that ultrastructural evaluation of undifferentiated neuroblastomas would appear to have prognostic value, particularly in cases lacking initial biochemical data or as an adjunct to biochemical studies.