Nobuo Takasugi

MASS SCREENING FOR NEUROBLASTOMA IN INFANTS IN JAPAN: Interim Report of a Mass Screening Study Group

A mass screening system for the early detection by means of a vanillylmandelic acid test of neuroblastoma in 6-month-old infants in Japan has been developed in eight districts. 16 of the 281 939 infants screened by this test had neuroblastoma, equivalent to a very high incidence of 1 in 17 621. 15 of the 16 children with neuroblastoma are alive; the other child died 1 month after surgery. This mass screening system for neuroblastoma used in infancy can help to improve prognosis in infants with this malignant disorder.

Effects of the mass screening of neuroblastoma in sapporo city

One hundred sixty‐seven cases of neuroblastoma in the Registry of Childhood Malignancies in Hokaido Prefecture from 1969 to 1984 were studied, using the age at diagnosis, the clinical stage at diagnosis, and the survival rate to assess the influence of the mass screening of neuroblastoma performed in Sapporo City since 1981. In Sapporo City, the capital of Hokkaido Prefecture, the condition of the three parameters improved significantly after the institution of mass screening had not yet been performed, no significant change was observed in any of the three parameters (48‐month survival rate changed only from 21.1% to 28.1%). Consequently, the improvement in Sapporo City was thought to be attributed to the effects of the mass screening.

Mass screening for neuroblastoma and mortality in birth cohorts

Mortality resulting from neuroblastoma in birth cohorts in both Sapporo City and the whole of Japan was investigated to evaluate the effects of a high‐performance liquid chromatography (HPLC) mass screening program, targeting on 6 month‐old infants. In Sapporo City, the non‐HPLC screened cohort showed no reduction in mortality at 4 years of age compared with the pre‐screening cohort. However, the HPLC screened cohort showed a reduction of 69% in mortality compared with the pre‐screening cohort. On a nation‐wide scale, there was a significant decline in mortality for the non‐HPLC screened cohort compared with the pre‐screening cohort; for the HPLC screened cohort for 1989‐1991, there was also a reduction in mortality for children younger than 2 years of age. The incidence of neuroblastoma at 1‐4 years of age in the HPLC cohort in Sapporo City was about half that in the pre‐screening cohort, along with and probably because of an increasing incidence among infants in the same cohort. Our findings suggest that HPLC screening may detect some poor‐prognosis neuroblastoma cases at early stages, thus providing for more favorable therapy. Int. J. Cancer 71:552‐555, 1997.

Mass screening of neuroblastoma in Sapporo City, Japan.

In Sapporo City a mass screening program for neuroblastoma aiming at 6-month-old infants has been performed since April 1981. By March 1990, 136,001 infants were screened; 26 true-positive cases of neuroblastoma and six false-negative cases were detected. The sensitivity of the mass screening method was about 80% throughout the 9 years. During the 9-year period, a total of nine children with neuroblastoma who were not screened were also identified. Clinical stage, age at diagnosis, and survival rate for the 32 patients who were screened (26 true positives and six false negatives) were much more favorable than those for the nine patients who were not screened. A remarkable decrease in the incidence of cases of neuroblastoma with advanced clinical stages over 1 year of age, especially among children 1-4 years of age, was noted after the start of the mass screening. The mortality from this tumor in children up to 4 years of age significantly decreased after the start of the urinary screening program. Rescreening at 14 months of age was begun in April, 1991 in Sapporo City. Performing two screening examinations decreases the probability of overlooking a patient. Thus, it is expected that tumors missed on the first screening would be detected by the second screening.

Improvement in prognosis of neuroblastoma through mass population screening

Since April 1981, the city of Sapporo, Japan, has conducted a mass screening program to measure urinary vanillylmandelic acid and homovanillylic acid using high-performance liquid chromatography. This program was expanded to the entire island of Hokkaido in October 1987. Mass screening proved beneficial, resulting in an increase in patients diagnosed with neuroblastoma under 1 year of age from 17% to 66%, an increase in stage I cases from 9% to 26%, an increase in stage III cases from 9% to 32%, and an increase in the tumor resectability rate from 15.1% to 58%. These improvements raised the 5-year survival rate for neuroblastoma from 23% to 66.7%. An additional study of these mass screening cases using Shimadas classification showed a wide range of histopathological distribution, and it demonstrated the usefulness of such a program in identifying the tumors most in need of early treatment.

Cases of neuroblastoma missed by the mass screening programs.

ABSTRACT: Twenty-two reported cases of neuroblastoma missed by the mass screening programs were reviewed (six cases in Sapporo City where a quantitative measurement for both vanillylmandelic acid (VMA) and homovanillic acid (HVA) is used and 16 cases in the districts of qualitative judgment only for VMA), and some potential factors for missing a patient were discussed. Most of the 22 patients were diagnosed over 12 mo and had advanced clinical stages at diagnosis (III or IV). Of the 17 cases whose outcome in prognosis was available, nine cases were dead and only three cases were alive without any trace of tumor. Fluctuation in the amounts of urinary VMA and HVA seemed to be one of the causes for missing a patient, especially with a small tumor. The comparison about tumor wt, VMA and HVA amounts, and clinical stage between the 22 true positive cases in Sapporo City and 46 ones in the districts of qualitative methods, and the difference in detection rate between the two groups suggested that the qualitative methods missed more patients with a small tumor. The patients who had abnormally high amounts of HVA with low amounts of VMA accounted for a fairly large part of the missed cases in Sapporo City as well as in the districts of qualitative methods. To the contrary, no patient of this type was found even among the 22 true positive cases in Sapporo City.

Microassay system for newborn screening for phenylketonuria, maple syrup urine disease, homocystinuria, histidinemia and galactosemia with use of a fluorometric microplate reader

Abstract Microfluorometry for measuring phenylalanine, branched-chain amino acids, homocysteine and histidine in dried blood spots is presented as a new mass screening method for phenylketonuria, maple syrup urine disease, homocystinuria and histidinemia, respectively. Simple and rapid determinations of the metabolites are achieved by adapting each of the optimum fluorogenic reactions to a microplate scale followed by using a highly sensitive microplate reader. Each assay for several hundreds of samples can be completed within 3 h, with fully calculated results by an on-line microcomputer. The proposed system, both with simple procedure and quantitative results, is useful for the multiple routine screening for the four aminoacidopathies, in addition to galactosemia as we reported earlier [20]. (1) The usage of a microplate system for routine microplate screening might be able to open a new style of mass-screening. (2) Measurement of homocysteine seems to be more desirable than measuring methionine in order to detect classic homocystinuria, and to enable detection of the remethylatine defects. However, the recovery procedure of homocysteine needs to be improved; furthermore, the measuring of three branched-chain amino acids will be better than determining only leucine for detecting a mild form of maple syrup urine disease or other conditions which increase the levels of these amino acids. The manner in which we measure phenylalanine in our method is more sensitive than others using the microplate system.

Gestational transient hyperthyroxinaemia (GTH): screening for thyroid function in 23 163 pregnant women using dried blood spots

Transient elevation of serum free T4 (gestational transient hyperthyroxinaemia; GTH) occurs occasionally during normal pregnancy, especially in early gestation. However, the frequency of GTH and its clinical features remain unclear to date. The aim of this study was to determine the occurrence rate of GTH and the relation between serum levels of hCG, free T4 (fT4), and TSH in a large number of pregnant women.

Incidence of neuroblastoma in Sapporo city.

The incidence of neuroblastoma in Sapporo City for the period before the enforcement of the mass screening of neuroblastoma (1974 to 1980) was compared with the period after it (1981 to 1987). No large difference was found in incidence between them. In 1981 to 1987 the occurrence cluster at 2 to 4 years of age found in the prescreening period disappeared and an accumulation of patients at 0 year of age was noted. The sensitivity of the mass screening was almost stable (76.9% to 80.0%) throughout the 7 years. By the mass screening system of Sapporo City, early detection will be expected in 60% to 70% of all the neuroblastoma patients, the deficiency of which is due to the patients who neglected the mass screening.

Mass screening and occurrence of neuroblastoma in Sapporo City

Abstract In Sapporo City from April 1981 to March 1986, 73,226 infants were screened for neuroblastoma and 24,636 were not screened. By March 1992, out of the screened group 15 true-positive cases and five false-negative cases were found. The 20 cases in this group give an incidence of 27: 100,000. Out of the unscreened group five patients were found during the same period, giving an incidence in this group of 20:100,000. Since the incidence in the screened. group was by 1.34-times higher than that in the unscreened group, it is possible that about 30% of the true-positive cases are those whose tumors regress spontaneously. However, since the incidences of cases 1–4 years of age and of cases with advanced stages in this same age group as well as the total mortality in the screened group were lower in the screened group than in the unscreened group, it is certain that the mass screening makes a contribution to early detection of this disease. Calculation from data of false-negative cases and unscreened cases showed that about half of the cases with poor prognosis might be caught by the mass screening. Calculation from the mortality data also showed that the mass screening might reduce deaths from neuroblastoma by about half.