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.     

Mass screening for neuroblastoma at 6 months of age: difficult to justify

BACKGROUND/PURPOSE: A statistical analysis of the mass screening for neuroblastoma in Japan based on a population study rarely has been reported. This study aims to evaluate retrospectively the effectiveness of mass screening at 6 months of age using the available population data. METHODS: The data on the neuroblastoma cases registered by the Committee for Pediatric Solid Malignant Tumors in the Kyushu area were analyzed based on both screened and unscreened populations in the Kyushu area. RESULTS: From 1988 to 1992, the cumulative incidence of neuroblastoma in children less than 5 years of age was 82 in 484,599 for screened children, and 11 in 92,966 for unscreened children, respectively. Fourteen of the 82 screened patients had negative findings at 6 months of age (MS-negative cases). No significant difference was observed in the cumulative mortality rates from neuroblastoma in children younger than 5 years of age between the screened children and the unscreened children. Six of seven patients who died among the screened children were MS-negative cases with stage III or IV disease. In addition, no significant difference was found in the cumulative mortality rates from the neuroblastoma cases in patients less than 5 years of age between the children screened from 1988 to 1992 (7 of 484,599) and all children from 1980 to 1984 (14 of 668,084). CONCLUSIONS:These findings suggests that the majority of the patients detected by mass screening had a favorable prognosis, and, mass screening in Japan for children less than 6 months of age was not observed to reduce the incidence and mortality from neuroblastoma. Therefore, mass screening at 6 months of age was not found to improve substantially the prognosis of patients with unfavorable neuroblastoma identified over 1 year of age, which is the primary purpose of such mass screening for neuroblastoma.     

Compliance in a screening program for neuroblastoma

OBJECTIVES: Whether or not spermicides can reduce the risk of human immunodeficiency virus (HIV) transmission remains an important question for the control of heterosexual HIV transmission. The authors provide estimates from a reanalysis of one of the few observational studies on the efficacy of condoms and spermicides, used separately and together, per vaginal contact. METHODS: In this reanalysis, three different models were used to assess the efficacy of spermicides and condoms: linear (Pearl index), exponential (maximum likelihood), and monotonic (marginal likelihood). RESULTS: Reported use of barrier methods among 27,432 contacts was as follows: condoms plus nonoxynol-9, 39%; condoms alone, 25%; nonoxynol-9 alone, 24%; and unprotected, 11%. Under all three models, the results indicate a strong protective effect for spermicidal suppositories. The Pearl index indicated that spermicide alone is apparently efficacious, but the efficacy per contact cannot be quantified with this approach. Maximum likelihood estimates for the efficacy of nonoxynol-9 alone and condoms (with or without nonoxynol-9) were 100% (95% confidence interval [CI95] = 43%, 100%) and 92% (95% CI95 = 79%, 100%), respectively. CONCLUSIONS: The data from this observational study suggest that spermicides may be efficacious in reducing the risk of HIV transmission.     

Bladder origin neuroblastoma detected by mass screening

A 5-HT2A receptor promoter polymorphism, -1438G/A, was reported to be significantly increased in patients with anorexia nervosa when compared with controls. In practice, many patients with anorexia nervosa suffer from mood disorders. Furthermore, 5-HT2A receptors are thought to play a role in the etiologies of mood disorders. Thus, we studied the polymorphism in 95 Japanese patients with mood disorders and 106 healthy Japanese controls. The allele frequency for the -1438G/A polymorphism did not differ between the patients and controls. In addition, the genotype frequencies did not differ according to the subdiagnosis, age of onset, family history of psychiatric illness or suicide attempts.     

False positive results in a neuroblastoma screening programme

One hundred eighty healthy subjects (90 men, 90 women; age range: 55 to 80 years) with no known cardiovascular disease were studied by ultrasonography. In each, the following measurements were obtained: the caliber and length of the abdominal aorta and inferior vena cava, and the caliber of the common iliac arteries and veins. The mean length of the inferior vena cava was found to be 95.2 mm, its mean caliber 18.4 mm. The mean length of the aorta was 83.1 mm, and its mean caliber was 15.9 mm. The mean caliber of the common iliac veins was 9.7 mm, while that of the common iliac arteries was 8.8 mm. There was a statistically significant relationship between vessel caliber and subject age; furthermore, the vessel caliber of the male subjects was found to be larger than that of the females by a statistically significant margin. There was also a statistically significant correlation between subject height and the length of the two major vessels; however, no statistically significant correlations were noted between the measured parameters and body weight. In comparison with the values reported in the standard textbooks and by contemporary cadaveric studies, our measurements of mean aortic and vena caval calibers were significantly lower. When the two side were compared, a statistically significant difference was noted only in the iliac arteries, where the right was larger than the left.     

Spontaneous regression of localized neuroblastoma detected by mass screening

PURPOSE: A retroperitoneal access is commonly used for open urological procedures. Since the introduction of the balloon dissecting technique by Gaur this anatomical route has also been used for laparoscopic surgery. We present our experience with retroperitoneoscopy in 200 cases. MATERIALS AND METHODS: From December 1992 to October 1997 a total of 200 retroperitoneoscopic procedures were performed in 197 patients 4 to 82 years old, comprising 78 nephrectomies, 50 renal cyst resections, 14 nephropexies, 11 ureterolyses, 8 retroperitoneal lymph node dissections, 8 renal biopsies, 6 adrenalectomies, 6 heminephrectomies, 6 pyeloplasties, 5 ureterolithotomies, 6 ureterocutaneostomies and 2 others. Of the patients 38 (19%) and 22 (11%) had undergone previous abdominal surgery, and kidney and ureter operations, respectively. Dissection of the retroperitoneal space was enabled by the use of a balloon catheter in 14, balloon trocar system in 93 and finger dissection technique in 93 cases. RESULTS: We classified 76 procedures (38%) as simple (renal biopsy, renal cyst resections, ureterocutaneostomy), 102 (51%) as difficult (adrenalectomy, nephrectomy, nephropexy) and 22 (11%) as very difficult (pyeloplasty, heminephrectomy, lymphadenectomy). There was a significant learning curve during the first 50 cases reflected by longer operating time, and higher complication, conversion to open surgery and open reintervention rates (14, 10 and 6%, respectively). In addition to the learning curve, mean operating time depended on the difficulty of the procedure, averaging 45 to 100 minutes for a simple, 95 to 185 for a difficult and 185 to 240 for a very difficult retroperitoneoscopy. In the last 50 cases the complication, conversion and reintervention rates (2, 4 and 2%, respectively) were acceptable for routine clinical application. CONCLUSIONS: After experience with more than 200 cases of retroperitoneoscopy the access technique has been significantly simplified. The procedure is standardized, safe and reproducible.     

Cystic fibrosis screening by sweat analysis: a critical review of techniques

Currently employed methods for the assay of electrolytes in sweat, relevant to the diagnosis of cystic fibrosis, are critically evaluated with particular reference to the measurement of electrical conductivity. Attention is drawn to the factors responsible for potentially large errors. On the basis of experimentation, supported by laboratory practice, recommendations are made for the reduction of these errors to clinically acceptable levels. Data concerning sodium and potassium content, electrical conductivity and osmolality of undiluted sweat collections are compared. The feasibility and comparative advantages of measuring sweat osmolality with a vapour pressure osmometer are discussed.     

Mass screening for histidinaemia:rationalization by selective thin layer chromatography. First results

Since 1974 histidine and urocanic acid was estimated by thin layer chromatography (TLC) in all newborn infants in whom histidine blood levels had to be controlled because of an abnormal Guthrie-test. This entailed using dried blood spotted on filter paper to rationalize newborn screening for histidinaemia thus reducing the work involved. Three cases of histidinaemia were found amongst 66.064 newborn infants. In order to find these, 830 initialy suspicious Guthrie tests had to be checked. This is a control frequency of 1:80. 384 controls were necessitated by inhibition-zones, 482 by initialy elevated blood levels. Histidine and urocanic acid concentrations generally correlated well in the TLC; only 9 newborn infants showed results suggesting histidinaemia (elevated histidine and absent urocanic acid). All three histidinaemias discovered by Guthrie-test aswell were among them, so that in the end, with only 9 controls combining Guthrie-test and TLC, the same effectiveness could have been reached, as compared to 830, when using the Guthrie-test alone.     

Newborn screening for inborn errors of metabolism: a systematic review

OBJECTIVES. To establish a database of literature and other evidence on neonatal screening programmes and technologies for inborn errors of metabolism. To undertake a systematic review of the data as a basis for evaluation of newborn screening for inborn errors of metabolism. To prepare an objective summary of the evidence on the appropriateness and need for various existing and possible neonatal screening programmes for inborn errors of metabolism in relation to the natural history of these diseases. To identify gaps in existing knowledge and make recommendations for required primary research. To make recommendations for the future development and organisation of neonatal screening for inborn errors of metabolism in the UK. HOW THE RESEARCH WAS CONDUCTED. There were three parts to the research. A systematic review of the literature on inborn errors of metabolism, neonatal screening programmes, new technologies for screening and economic factors. Inclusion and exclusion criteria were applied, and a working database of relevant papers was established. All selected papers were read by two or three experts and were critically appraised using a standard format. Seven criteria for a screening programme, based on the principles formulated by Wilson and Jungner (WHO, 1968), were used to summarise the evidence. These were as follows. Clinically and biochemically well-defined disorder. Known incidence in populations relevant to the UK. Disorder associated with significant morbidity or mortality. Effective treatment available. Period before onset during which intervention improves outcome. Ethical, safe, simple and robust screening test. Cost-effectiveness of screening. A questionnaire which was sent to all newborn screening laboratories in the UK. Site visits to assess new methodologies for newborn screening. The classical definition of an inborn error of metabolism was used (i.e., a monogenic disease resulting in deficient activity in a single enzyme in a pathway of intermediary metabolism). RESEARCH FINDINGS. INBORN ERRORS OF METABOLISM. Phenylketonuria (PKU) (incidence 1:12,000) fulfilled all the screening criteria and could be used as the 'gold standard' against which to review other disorders despite significant variation in methodologies, sample collection and timing of screening and inadequacies in the infrastructure for notification and continued care of identified patients. Of the many disorders of organic acid and fatty acid metabolism, a case can only be made for the introduction of newborn screening for glutaric aciduria type 1 (GA1; estimated incidence 1:40,000) and medium-chain acyl CoA dehydrogenase (MCAD) deficiency (estimated incidence 1:8000-1:15,000). Therapeutic advances for GA1 offer prevention of neurological damage but further investigation is required into the costs and benefits of screening for this disorder. MCAD deficiency is simply and cheaply treatable, preventing possible early death and neurological handicap. Neonatal screening for these diseases is dependent upon the introduction of tandem mass spectrometry (tandem MS). This screening could however also simultaneously detect some other commonly-encountered disorders of organic acid metabolism with a collective incidence of 1:15,000.(ABSTRACT TRUNCATED)     

Mass screening for prostate cancer in Japan

Since 1975 mass screening for prostate cancer has been performed in Japan. The Prostate Research Foundation has analysed the data every year that collected from all institutes performing a mass screening. Up to 1993, 67, 225 subjects were examined. The detection rate of prostate cancer was 0.69%. Approximately half of the cancer were stage B, and the subjects who have metastatic stage were only 20% and the pattern of stage seemed to be different from that of patients who visited hospitals. In Chiba prefecture the subjects lived in a district of south Boso peninsula received a mass screening for prostate cancer with total of 1,964 men from 1985, and 17 cancers were diagnosed (0.87%). The distribution of prostate-specific antigen (PSA) assayed with Tandem-R kit was examined using the stocked sera (n = 976) of the screening for prostate cancer in Chiba prefecture. The percentage of 0.05-4.0 ng/ml, 4.1-9.9 ng/ml, over than 10.0 ng/ml of the PSA, were 89.6%, 7.0%, 3.4%, respectively. This distribution is approximately as same as the previous reports by the United States and Canada.     

Benefits of screening mammography: a review for the primary care physician

BACKGROUND: Screening mammography, particularly for women in their 40s, has become a confusing issue for many physicians. Recent scientific and political controversies regarding screening guidelines have added to this confusion. METHODS: Many randomized clinical trials have shown the benefits of mammographic screening for women over the age of 50, and recent studies show a statistically significant benefit for women in their 40s as well. Understanding the screening controversy requires an understanding of the principle of screening for disease, the epidemiology of breast cancer, and the results of the many randomized clinical trials, particularly recent data from the Swedish two-county trials. An appreciation of the improvements in mammographic quality in recent years, and in the education of the radiologists who interpret these studies, will also heighten clinical acceptance of this screening technique. RESULTS: Both the American Cancer Society and American College of Radiology endorse annual mammographic screening for women over age 40, and there is compelling evidence to support these recommendations. CONCLUSION: Radiologists, primary care providers, surgeons, and pathologists should work together to enhance the benefits of and access to screening mammography.     

The psychiatric review of symptoms: a screening tool for family physicians

The psychiatric review of symptoms is a useful screening tool for identifying patients who have psychiatric disorders. The approach begins with a mnemonic encompassing the major psychiatric disorders: depression, personality disorders, substance abuse disorders, anxiety disorders, somatization disorder, eating disorders, cognitive disorders and psychotic disorders. For each category, an initial screening question is used, with a positive response leading to more detailed diagnostic questions. Useful interviewing techniques include transitioning from one subject to another rather than abruptly changing subjects, normalization (phrasing a question to convey to the patient that such behavior is normal or understandable) and symptom assumption (phrasing a question to imply that it is assumed the patient has engaged in such behavior). The psychiatric review of symptoms is both rapid and thorough, and can be readily incorporated into the standard history and physical examination.     

A population-based study of the usefulness of screening for neuroblastoma

BACKGROUND: Neuroblastoma has many characteristics which suggest that preclinical detection might improve outcome. The Quebec Neuroblastoma Screening Project was initiated to determine whether mass screening could reduce mortality in a large cohort of infants. As an early endpoint, we report whether screening could reduce the incidence of poor-prognosis neuroblastoma in children with advanced-stage disease over 1 year of age. METHODS: All 476,603 children born in the province of Quebec during the 5-year period of May 1, 1989, to April 30, 1994, were eligible for urinary assay of homovanillic acid and vanillylmandelic acid at 3 weeks and 6 months of age. Children with a positive screen were referred to one of four paediatric cancer centres in the province for uniform evaluation and treatment if necessary. Standardised incidence ratios (SIRs) were calculated for neuroblastoma in the province and two similar population-based controls, the state of Minnesota and the province of Ontario, during the same period of time and with similar ascertainment procedures. FINDINGS: Compliance with screening in Quebec province was 91% at 3 weeks (n = 425,816) and 74% at 6 months (n = 349,706). Through July 31, 1995, with a follow-up of the birth cohort of 15-75 months, 118 cases of neuroblastoma were diagnosed, 43 detected preclinically by screening, 20 detected clinically before screening at 3 weeks of age, and 55 detected clinically after 3 weeks of age having normal screens (52) or never screened (3). Retrospective analysis of stored samples confirmed that 49 of 52 patients missed by screening had levels of catecholamine metabolites that were too low to be detected at 6 months or earlier. Based on US Surveillance, Epidemiology and End Results data, 54.5 cases of neuroblastoma would have been expected in Quebec province during the study period, for an SIR of 2.17 (95% CI 1.79-2.57, p < 0.0001). For the two control groups, 43 and 80 cases of neuroblastoma were detected, respectively, compared with 37.9 and 85.4 expected, overall SIR 1.00 (not significant). SIRs for Quebec province by age at diagnosis in yearly intervals show a marked increased incidence under 1 year of age (SIR 2.85, 2.26-3.50), with no reduction in incidence in subsequent years. Limiting analysis to only patients diagnosed over 1 year of age with advanced-stage disease, 22 cases were detected in Quebec province versus 14.4 expected (SIR 1.52, 0.95-2.23). Data in the two control groups show no significant increase or decrease in any-stage disease in children under or over the age of 1 year, except for an increase in early-stage disease in Minnesota children over 1 year: 10 versus 3.8 expected (SIR 2.67, 1.27-4.58). INTERPRETATION: Screening for neuroblastoma increases the incidence in infants without decreasing the incidence of unfavourable advanced-stage disease in older children. It is unlikely that screening for neuroblastoma in infants will reduce mortality for this disease.     

10 years' neuroblastoma screening in Europe: preliminary results of a clinical and biological review from the Study Group for Evaluation of Neuroblastoma Screening in Europe (SENSE)

Between January 1986 and May 1996, 870,313 children were tested in European neuroblastoma (NB) screening programmes. Among these children, 82 cases of NB (age range 4-24 months, median 11 months) were detected by screening. 83% of the patients had localised NB and 17% were diagnosed with generalised NB (stage 4, 10%; stage 4s, 7%). Unfavourable biological markers (MYCN amplification, loss of heterozygosity (LOH) 1p36, DNA di/tetraploidy) were observed in 14% of 76 biologically examined cases. The median follow-up time of all the patients was 21.5 months (range 1-101 months). To date, 69 patients are in complete remission (CR) and 2 patients have died due to therapy (stage 4, 1 patient; stage 3, 1 patient with unfavourable markers). Apart from screened patients, 16 other patients with NB were found who had previously had a normal screening test, i.e. 'false negative' patients (age range 10-41 months, median 31.5 months). The median interval between screening and diagnosis was 24.5 months (range 6-35 months). 11 of the 'false negative' patients suffered from generalised NB (stage 4) and 5 had localised NB at diagnosis. Unfavourable biological markers were observed in 7/12 patients. 5 patients have died, 2 achieved partial remission and 9 CR. 9 of the 11 patients with unfavourable biological markers diagnosed due to NB screening are currently in CR. It is very likely that, among the patients without unfavourable biological markers, we detected tumours which may have regressed spontaneously. These children may have undergone 'unnecessary,' but unavoidable, diagnostic procedures and therapy. To reduce the number of 'false negative' patients, a later screening could be helpful and should be evaluated.     

Inflammatory process and screening methods for anti-inflammatory agents (a review)

The "Konfigurationsfrequenzanalyse" (KFA) is a method proposed by Lienert to detect syndromes. Using examples we criticize the definition of a syndrome used for a KFA, and we thus criticize the interpretation of the results of a KFA. Furthermore, we describe briefly a backward selection procedure of multiplicative models for contingency tables. This procedure may be used to find simple patterns of association for several symptoms.     

Imaging of neuroblastoma in patients identified by mass screening using urinary catecholamine metabolites

Comparative ultrastructural observations are presented of the distended bladder of a hibernating dormouse (Muscardinus avellanarius) and a relaxed organ taken from an active animal. The distended bladder of the hibernating animal has an extremely thin wall lined with a three-layer urothelium. An osmiophilic coat lines the luminal surface of the urothelium in the hibernating animal, but it is very thin indeed in the specimen from the active dormouse. In the urothelium of the distended bladder, a larger number of fusiform vesicles (FVs, typical structures of the urothelium with asymmetric unit membrane) is found. On the contrary, lysosomes, multivesicular bodies, and interdigitation of plasma membrane between adjacent cells are all more frequent in the relaxed bladder of the active dormouse. Results suggest that hibernating animals can be a useful model for investigating the biology of epithelial cells in the mammalian bladder.     

Effectiveness of screening for osteoporosis by bone density measurement for the prevention of fractures: a review of the evidence]

To review evidence on the benefits of screening women and men for osteoporosis, a Pub Med search was performed in English papers published between 1990 and 2002. We used data from a cohort study to estimate risk of fracture from bone mineral density. Bone mineral density measured by dual X-ray absorptiometry (DXA) can predict bone fracture among elderly women, peri- and early post-menopausal women, and elderly men. It is recommended that all white women older than 65 years be screened routinely for osteoporosis. We suggest that Japanese elderly women should receive BMD measurements as a screening, but we have still issues to be solved including age from when the screening should be started, methods, and how to treat the women found to have osteoporosis at the screening. For peri- and postmenopausal women and elderly men, it might be beneficial to measure BMD as a screening and start treatment for those patients found to have osteoporosis. However, incidence of fractures for these people is lower than that for elderly women. One bone mass measurement can predict bone fracture risk for as long as over 10 years or more, but predictive ability of BMD decreases with time. Therefore, cost effectiveness needs to be reviewed to determine the benefits of screening among peri-menopausal women and men. Although bone assessment by quantitative ultra sound (QUS) method by ultrasound can also predict future fractures, only a relatively small number of longitudinal studies have been conducted in the Western countries, and there is no established evidence by means of longitudinal studies among Japanese. It is necessary in Japan to seek such evidence, however, since this method is widely used for an osteoporosis examinations.     

Mass screening for prostate cancer--how to eliminate clinically insignificant cancer

The ultimate aim of the mass screening program for prostate cancer is to decrease prostate cancer mortality, which can be demonstrated only in a well-designed and well-controlled trial comparing screened and unscreened populations. However, no trials have been performed to demonstrate the effect of this program. Some reports claimed that such a program includes the high possibility of detecting clinically insignificant cancer, for example, latent cancer. In this paper, early cancer detection and treatment in mass screening program are discussed.     

Mass screening programs for breast cancer in France. Comparative evaluation

OBJECTIVE: The purpose of this work was to comparatively assess the results of mass screening programs for breast cancer implemented in six French departments in 1986, within the scope of the National Fund for Health Prevention, Education and Information of the National Health Insurance Office of Salaried Workers. MATERIAL AND METHODS: The data collected by the screening centres were analyzed by ten assessment teams that were independent from the program promotion staff, all using the same evaluation form. A complementary population study performed in eight French districts then, allowed assessing the frequency of self-referred screening (mammography performed out of program). RESULTS: The rate of participation in screening programs, in relation to the invited population, ranged from 21 to 48%, according to the district (36% in average). This low participation was probably related to the extent of self-referred screening. In fact, 19 to 40% of women, according to the district, had previously had a screening mammographic coverage: rate was around 68% in women aged 50 to 69 years. Positive findings with mammography ranged from 4.5 to 15.8% (10.1% in average), while intervention rates ranged from 0.7 to 1.6% and detection rates from 3.8 to 6.2%. The ratio between benign tumors and cancers ranged from 0.7 to 2.1 according to the district. In order to enlighten the judgement on French results, we propose a comparison with the international standards in force. CONCLUSION: The various experiences with breast cancer screening in France show that this screening is technically feasible on the basis of existing medical structures. However, some criteria are still below the expected values, especially if compared with international standards. This result is probably accounted for by the high rate self-referred screening before age 40 in France. In these conditions, the question is whether extending breast cancer screening programs in France is an appropriate course of action.     

Mass screening of colorectal cancer by general practitioners in France: what is the real target population?

OBJECTIVES: People at high risk of colorectal cancer, due to familial or personal history, or to specific symptoms, are considered not to be concerned by mass screening by Haemoccult test. The aim of this study was to investigate people aged 50 to 74 with high risk of colorectal cancer among general practitioners' practices in the department of Calvados (France). METHODS: A random sample of 200 general practitioners were asked to systematically fill out a questionnaire on Haemoccult II proposal for 50-74 year-old patients for a whole week. RESULTS: Participation rate of general practitioners was 58.5%. According to our findings, 13% of 50-74 years patients are considered not be concerned by mass screening, due to familial or personal history, or to specific symptoms. CONCLUSIONS: Colorectal cancer screening protocol have to be fit to level of risk of colorectal cancer. Involvement of general practitioners in colorectal cancer mass screening allows identification of high risk people who can then be managed with a more suitable screening protocol.