Nakagawara A, Zaizen Y, Ikeda K, Suita S, Ohgami H, Nagahara N, Sera Y, Akiyama H, Kawakami K, Uchino J
Department of Pediatric Surgery, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Cancer. 1991 Nov 1;68(9):2037-44. doi: 10.1002/1097-0142(19911101)68:9<2037::aid-cncr2820680932>3.0.co;2-c.
The mass screening of neuroblastoma has been undertaken in Japan by measuring urinary vanillylmandelic acid (VMA) and homovanillic acid (HVA) in all infants at the age of 6 months. This program may not only improve the prognosis but also provide important insights into the biology and evolution of human neuroblastoma. The authors studied and discuss the clinical significance of the N-myc oncogene, catecholamine metabolism, and other tumor markers in 43 patients with neuroblastoma who underwent the urinary screening test at 6 months of age. Thirty patients were found by the screening, and 13 were negative at the screening but later had a tumor. In the former group, the tumors were mostly in early stages (Stage I, 12; Stage II, 11; Stage III, seven), no amplification of N-myc was observed, and all patients are alive without disease. Although two patients whose urine at the screening showed elevated VMA and HVA levels and accidentally were not treated for 13 and 17 months, there was no change in the values of VMA and HVA during that time. However, in the latter group, the tumors were mostly in advanced stages (Stage I, one; Stage III, four; Stage IV, eight) and N-myc amplification was observed in seven of 13. Only two of these 13 are alive without disease. The age at diagnosis of the screening-negative group was 23 months compared with 8 months in the patients identified by screening, and the pattern of catecholamine metabolites in the screening-negative group tended to be dopaminergic with a low VMA-HVA ratio, especially in cases with N-myc amplification. These data suggest that the screening-positive patients with neuroblastoma may have favorable characteristics, and the biology of these tumors may be different from that of screening-negative later-presenting tumors. They also suggest that there may be at least two distinct subsets of neuroblastoma. For the early detection of the poor prognostic neuroblastomas, the measurement of urinary dopamine with VMA and HVA at later ages, such as 1 to 2 years, should be considered.
在日本，通过检测所有6个月大婴儿尿液中的香草扁桃酸（VMA）和高香草酸（HVA）来进行神经母细胞瘤的大规模筛查。该项目不仅可能改善预后，还能为人类神经母细胞瘤的生物学特性和演变提供重要见解。作者研究并讨论了43例6个月大时接受尿液筛查试验的神经母细胞瘤患者中N - myc癌基因、儿茶酚胺代谢及其他肿瘤标志物的临床意义。筛查发现30例患者患有肿瘤，13例筛查时为阴性但后来患了肿瘤。在前一组中，肿瘤大多处于早期阶段（I期12例；II期11例；III期7例），未观察到N - myc扩增，所有患者均无病存活。尽管有2例筛查时尿液VMA和HVA水平升高的患者意外地分别有13个月和17个月未接受治疗，但在此期间VMA和HVA值没有变化。然而，在后一组中，肿瘤大多处于晚期阶段（I期1例；III期4例；IV期8例），13例中有7例观察到N - myc扩增。这13例中只有2例无病存活。筛查阴性组的诊断年龄为23个月，而筛查发现的患者为8个月，筛查阴性组儿茶酚胺代谢产物的模式倾向于多巴胺能，VMA - HVA比值较低，尤其是在有N - myc扩增的病例中。这些数据表明，筛查呈阳性的神经母细胞瘤患者可能具有良好的特征，这些肿瘤的生物学特性可能与筛查阴性后来发病的肿瘤不同。它们还表明，神经母细胞瘤可能至少有两个不同的亚组。为了早期发现预后不良的神经母细胞瘤，应考虑在1至2岁等较晚年龄测量尿液中的多巴胺以及VMA和HVA。
