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We tried to discriminate between cases of spontaneous regression and non-regression during mass screening for neuroblastoma, taking advantage of differences in respect to the urinary homoranillic acid/vanillyl mandelic acid (HVA/VMA) ratio and the original tumor site among true positive, false negative and natural occurrence cases. After classifying them into a total of six groups depending on the two factors, ratio: < 1, 1-2 or > or = 2 and tumor site: adrenal or extra-adrenal in origin, we calculated the mathematical probability of a given true positive case being one of spontaneous regression. A tumor of extra-adrenal origin was likely to regress spontaneously, especially one with an HVA/VMA ratio < 1 or > or = 2 (82.2-100%). A tumor of adrenal origin with an HVA/VMA ratio < 1 seemed unlikely to regress spontaneously (0-4%). The present method, employing simple preoperative information, would be useful in future for the selection of true positive cases which should be observed without treatment.

Employing 421 urine samples taken randomly from normal infants and 294 samples from infants with neuroblastoma, we investigated the application of values of vanillylmandelic acid (VMA), homovanillic acid (HVA) and square root of VMA2 + HVA2 to discriminate between patients and normal infants. The establishment of an HVA cut-off level is virtually impossible because of its low sensitivity. In contrast, VMA sensitivity is high, and that of square root of VMA2 + HVA2 is very similar to that of VMA although it includes HVA. Although VMA appears to be able to discriminate well, discrimination employing VMA alone would be dangerous because cases with normal VMA and abnormal HVA would be missed, especially in the first screening for which a mechanical discrimination is performed. Overlooking such cases can be avoided by the adoption of the function square root of VMA2 + HVA2. The present study suggests that the combined use of variables can be more effective than using them separately.

The amounts of vanillylmandelic acid (VMA), homovanillic acid (HVA), and catecholamines (adrenaline, noradrenaline, and dopamine) in 24-hr urine specimens of 10 infants with neuroblastoma detected through mass screening in Sapporo City (patient group) were compared with those of 24 healthy infants (control group). The ages of the infants of both groups ranged from 6 to 11 months, which agrees with the age when mass screening is performed. For VMA and HVA, the mean value plus two or three times the standard deviation of the control group clearly separated the two groups in the units of mg/day, microgram/mg of creatinine, mg/kg/day, and mg/m2/day. The cut off values of 24 micrograms/mg of creatinine for VMA and 25 micrograms/mg of creatinine for HVA are now being used by us for assaying 24-hr urine specimens. No significant difference was found between the groups in levels of catecholamines, but their data were thought to be useful as normal values, since few published data regarding their normal values are available.

The establishment of cut off values in vanillylmandelic acid (VMA) and homovanillic acid (HVA) in 24-hr urine specimens for the purpose of separating true positive cases from normal infants has been discussed. The specimens were collected at the time when thorough examinations under a mass screening programme for neuroblastoma were taking place, and data from 17 infants with neuroblastoma (patients) and 50 healthy infants (controls) have been employed. The function square root VMA2 + HVA2 = 34 (micrograms/mg of creatinine) separated the two groups with no overlapping cases. This function represents the distance from the origin of the VMA-HVA co-ordinates, and is thought to be one of the most reasonable discriminant methods when considering the distribution pattern of the data for normal cases and patients.

Seasonal variations in urinary levels of vanillylmandelic acid (VMA) and homovanillic acid (HVA) have been investigated over a two-year period, using 31,466 filter-paper specimens of urine from infants of 6 months of age who underwent Sapporo City's screening for neuroblastoma. Levels of both VMA and HVA (micrograms/mg creatinine) were significantly higher in summer (11.48 +/- 7.40, n = 7,569, and 18.70 +/- 8.18, n = 7,582, respectively) than in winter (10.72 +/- 5.76, n = 8,143, and 16.46 +/- 7.17, n = 8,148, respectively) throughout the two years (P less than 0.01, t-test). Although the cause of this difference could not be found, its actual clinical relevance was thought to be small since there was no significant relation between monthly rate of re-screened infants and monthly mean levels of VMA or HVA (P greater than 0.05, Spearman-Rank correlation).