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Enhanced expression of N-myc messenger RNA in neuroblastomas found by mass screening.

A substantial fraction of neuroblastomas found by mass screening have been suggested to regress spontaneously because of the high incidence of infantile neuroblastomas in the screening population. In this study, 70 neuroblastomas were analyzed for expression of proto-oncogenes related to neuronal differentiation to clarify the biological significance of proto-oncogene expression in the screening-positive and -negative tumors. The tumors consisted of 39 neuroblastomas found by screening (group 1), 16 non-N-myc-amplified neuroblastomas found by clinical symptom(s) (group 2), and 15 N-myc-amplified neuroblastomas found by clinical symptom(s) (group 3). The expression of c-src, trk A, and N-myc in tumor tissues was analyzed by quantitative RNA PCR. Neuronal c-srcN2 expression varied significantly in the following order: group 1 > group 2 > group 3. The level of expression of trk A was markedly reduced in group 3 but did not differ in groups 1 and 2. Most tumors in group 3 overexpressed N-myc. However, N-myc expression in group 1 was significantly higher than that in group 2. Thus, the characteristics of proto-oncogene expression in screening-positive tumors included enhanced expression of c-srcN2 and N-myc mRNA, regardless of nonamplification of N-myc. Our results suggest that the role of N-myc differs in neuroblastomas detected by screening and in N-myc-amplified tumors.

Disease-Free Survival↗

Mass screening for Wilson's disease: results and recommendations.

Wilson's disease is a treatable inherited disorder of copper metabolism. Established treatments include the use of oral chelating agents and the establishment of a minimum copper diet, although prognosis mainly depends on the extent of liver or nervous system damage present before treatment. Once irreversible damage has occurred, the effect of these treatments is diminished and the patient's quality of life compromised. Therefore, the establishment of a mass screening system able to detect Wilson's disease patients presymptomatically has been discussed. Recently, a monoclonal antibody specific to holoceruloplasmin has been developed. This antibody was used in a nationwide screening trial of 126,810 newborn infants, but no Wilson's disease patients were identified. However, three patients out of 24,165 were diagnosed with Wilson's disease using this specific antibody in a screening performed during the period from late infancy to elementary school. The age of 3 years is thought to be the best point for Wilson's disease mass screening. In this paper, a review of mass screening for Wilson's disease in Japan using a specific monoclonal antibody to holoceruloplasmin is presented.

Antibodies, Monoclonal↗

[The investigation of age-specific PSA reference range as the cut-off values in the mass screening for prostatic cancer].

BACKGROUND: The objective of this study is to determine age-specific PSA reference ranges in Japanese healthy men and investigate the effectiveness of these ranges as the cut-off values in the mas screening for prostatic cancer. METHODS: The study included a total of 5,206 male aged from 55 to 89 years old who wished to submit the mass screening for prostatic cancer in an urban area of Kyoto in 1995-1997, but had no evident prostatic cancer. We measured serum PSA levels by the filter paper method (Delfia PSA kit). RESULTS: We found the increase in serum PSA levels with the advancing age. With the 95th percentile for serum PSA as the upper limit, the age-specific PSA reference ranges were determined to be 2.1 ng/ml for patients aged 55 to 59 years old, 3.2 ng/ml for 60 to 69 years old, 4.4 ng/ml for 70 to 79 years old, 6.5 ng/ml for 80 to 89 years old. If we used these ranges as the cut-off values in the mass screening this time, five cases from 76 to 89 years old of prostatic cancer were overlooked. CONCLUSIONS: We found the increase in serum PSA levels with advancing age. But the positive proof of using this range to a mass screening for prostatic cancer was not certified, because time incidence of prostatic cancer in the examinees was uncertain and there is a possibility of overlooking some cases.

Age Factors↗

[A pilot study of mass screening program for prostatic cancer by means of prostate specific antigen (PSA) filter paper method].

BACKGROUND: Mass screening program for prostatic cancer (PC) using prostate specific antigen (PSA) filter paper method was performed in an urban area of Kyoto in 1995. METHODS: In the primary study, males more than the age of 55 years were examined by PSA (Delfia PSA kit) with blood samples on a filter paper. The cut-off values were set at 4 and 10 ng/ ml. Subjects whose PSA level ranged from 4.1 to 10.0 ng/ml (gray zone) were examined by digital rectal examination (DRE), transrectal sonography (TRS) and PSA density (PSAD; more than 0.15) in the secondary study, then the suspected subjects of PC underwent 6 sextant biopsies under interventional ultrasound. Subjects whose PSA level were more than 10.1 ng/ml were biopsied directly. RESULTS: Of 3,749 males who took the annual health checkup system organized by the government, 2,387 males wished to submit this screening. Among them, 2,217 (92.9%) showed a negative PSA, 107 belonged to the gray zone and 43 had a PSA more than 10.1 ng/ml. Of these, 102 subjects underwent biopsy. PC was finally detected in 28 (1.2%). The positive predictive value for positive PSA and gray zone PSA was 46.3% and 8.4%, respectively. In the detected cancers, 17 cases (60.7%) belonged to Stage B, 5 (17.9%) to Stage C and 6 (21.4%) to Stage D. CONCLUSION: The results suggested that this system of mass screening program for PC combined with the annual health checkup was suitable for the future "national-level" screening.

Aged↗

Mass-screening of neuroblastoma using urine from infants by high-performance liquid chromatographic method: results of first (6th month) and second (14th month) screening.

To detect neuroblastoma in early stages, mass-screening of this tumor was carried out by HPLC method using the urine of six-month-old infants. Screening began in April, 1981, and a total of 42 cases were detected by December, 1994. The incidence of detection was about 1:5,000 babies tested. All of these patients have survived without relapses except one, who died of surgical complications. Nevertheless, tumors developed at later stages in 14 cases from the group which resulted negative at the 6-month screening. To determine whether such tumors could be detected by a second check, a 14-month screening was carried out, beginning in April, 1991. By December, 1994, 3 patients with neuroblastoma were found among 41,809 babies tested, and were subsequently treated. While one of these three patients was not screened at 6 months, the other two had shown approximate cut-off values in urinary VMA as well as HVA at their 6-month screening. Therefore, if the tumors had already existed at the 6-month screening, and had grown gradually until the second check at 14 months, at least some of these tumors were of the late-onset variety and could have been detected at an earlier stage.

Chromatography, High Pressure Liquid↗

Evaluation of a mass screening program for stomach cancer.

To evaluate a mass screening program for stomach cancer, we followed 32,789 subjects for 6.1 years by means of a record linkage to a population-based cancer registry. The results show that the mortality from stomach cancer among those studied decreased by 9% as compared with the expected number calculated on the basis of the sex- and age-specific rates among the general population. When the study subjects were limited to those aged 40-59 years, the decrease in stomach cancer deaths became more marked, i.e., a 26% decrease was observed. Because this study is not a controlled trial, the results must be interpreted with the reservation that some biases were present in the study subjects.

Adult↗

Extirpation of mass-screened adrenal neuroblastomas by retroperitoneoscopy.

BACKGROUND: A mass-screened neuroblastoma (MSN) shows low-grade malignancy. Although the tumor is small, open laparotomy requires a large incision. PURPOSE: Extirpation by retroperitoneoscopy (ER) was performed in children with MSN to reduce the surgical stress. METHODS: The indications for ER were (1) MSN originating from the adrenal gland and (2) a tumor size of less than 4 cm. Between January 2000 and June 2002, 6 children (mean age: 8.5 +/- 0.6 months) underwent ER. RESULTS: All children successfully underwent ER and no conversion of laparoscopy to open surgery was required. The only complication in one patient was a peritoneal tear. Oral intake was possible in all children the day after the operation. No port site metastasis or local recurrence was observed during follow-up (15 to 29 months). CONCLUSIONS: Adrenal MSN less than 4 cm were successfully extirpated by ER. This method has the advantage of allowing patients an early return to eating and has no risk of postoperative ileus. ER is an available surgical technique for children with MSN less than 4 cm.

Adrenal Gland Neoplasms↗

Mass screening for hepatocellular carcinoma: experience in Hokkaido, Japan.

Mass screening for liver cancer based mainly on abdominal ultrasound was begun in major cities of Hokkaido, Japan, in November 1981, to enable early detection and treatment of hepatocellular carcinoma (HCC). Serum alpha-fetoprotein levels were also measured to minimize false negative studies. Examinees included those who sought liver disease screening as well as high risk individuals: hepatitis B surface antigen carriers and those with a past or current liver disease, history of blood transfusion, family history of liver cancer, and more recently those with positive anti-hepatitis C antibodies. The examination was carried out on each Saturday and Sunday as one round, and by February 1992 48 rounds had been performed. A total of 8090 individuals were investigated, and HCC was detected in 91 with a detection rate of 1.12%. This rate was 1.6% among 5684 individuals who were selected for high risk. Cumulative rates of survival among these patients were 79.0% at 1 year, 43.8% at 3 years, 19.3% at 5 years and 15.4% at 7 years. These survival rates were comparable with those for the patients with HCC diagnosed during follow-up of chronic liver disease and treated at our hospital. The cost for detecting one HCC patient in this programme was 2,660,000 yen (approximately US$25,000), which was less than those for some other types of cancer in a similar setting. Considering the high detection rate in this programme, we feel that similar programmes should be encouraged and supported.

Carcinoma, Hepatocellular↗

Adaptation of the meconium drug test for mass screening.

For purposes of mass drug screening, the procedure for analysis of meconium for drugs was modified into a one-step extraction and analysis by enzyme immunoassay. The accuracy of this modified method was tested by comparing the results of simultaneous analysis of 61 meconium samples for cocaine opiate and cannabinoid metabolites by both the original and the modified methods. In 61 samples analyzed, opiate was detected in 8 (13%) samples by the original method and in 9 (15%) by the modified method; cocaine was detected in 39 (64%) samples by the original method and in 39 (64%) by the modified method. The concordance between the negative and positive results of the modified versus the original methods was 98% and 100%, respectively, for opiate and 95% and 98%, respectively, for cocaine. Only one sample was positive for cannabinoid. Thus a comparison of positive results for cannabinoid was not done; however, all the negative results obtained by the modified method were confirmed by the original method. The clinical experience of mass meconium drug testing using the modified method in 1991 is also reported. In four centers tested (total tests = 4409), the prevalence of presence of drug was consistent with the high- or low-risk status of the population. This simplified, rapid procedure can be performed in most clinical laboratories. This adaptation has made the meconium drug test feasible for large-scale clinical and research use.

Cannabinoids↗

Laterality of the performance of glaucoma mass screening using frequency-doubling technology.

PURPOSE: This study investigated laterality during the performance of glaucoma mass screening with a frequency-doubling technology perimetry test. MATERIALS AND METHODS: A frequency-doubling technology screening mode (C-20-1, version 2.6) test was performed on both eyes of 14,784 persons. Subjects with visual field abnormalities detected by the frequency-doubling technology test or with fixation error underwent retesting without a specified interval for rest. Consequently, 206 subjects who fulfilled the screening criteria of the frequency-doubling technology-based glaucoma screening protocol [FDT-GSP(+)] were further investigated using the Humphrey visual field analyzer (30-2). As a result, 74 right eyes and 57 left eyes were shown to have definite glaucoma. RESULTS: Frequency-doubling technology data for the left eye demonstrated a significantly (P<0.001) higher rate of artifacts, such as no reproducibility of results between the first and second tests (left/right: 2.4%/1.7%) as well as fixation errors (left/right: 2.8%/1.0%). The false-positive rate of the FDT-GSP for glaucoma was more than 1.5-fold higher in the left eye than in the right eye (16.3%/9.8%). In the case that either eye exhibited FDT-GSP(+), the positive predictive value of the FDT-GSP for definite glaucoma in the left eye was almost half of that in the right eye (28.4% vs. 53.8%). Specificity of the FDT-GSP for detection of definite glaucoma also exhibited a lower trend (P = 0.097) in the left eye (44.6%) than in the right eye (55.3%), but the sensitivity of the test was similar in both eyes (91.2% vs. 90.5%, respectively). CONCLUSIONS: When frequency-doubling technology-based mass screening is performed on the general population, performance is lower for the left eye than for the right eye. This performance disparity is likely to be primarily associated with a difference in specificity.

Adult↗

Evaluation of the effectiveness of mass screening for uterine cancer in Japan: the potential years of life lost.

To evaluate the effectiveness of mass screening for uterine cancer in Japan, we compared the changes in the age-adjusted rates of potential years of life lost (PYLL) due to uterine cancer between 1969 and 1972 to 1973 through 1977 between the high coverage-rate (intensively screened) areas and the comparable control areas. The percent reduction in the average age-adjusted rate of PYLL due to uterine cancer and the years of life saved per 100,000 females were greater in the high coverage-rate areas than in the control areas. These results suggested that mass screening programs for uterine cancer contribute to saving years of life.

Adult↗

[Mass screening for endometrial cancer according to the Law of Health for the Elderly].

Due to the gradual increase of endometrial cancer, mass screening for this type of cancer began from 1987 in Japan in accordance with the Law of Health for the Elderly. However, a screening system for endometrial cancer has many controversial problems when compared with that for cervix cancer. Criteria for screening, methods of screening, management after screening, and executive systems are all controversial points in the performance of mass screening. The actual condition in the detection of endometrial cancer in Fukuoka Prefecture based on a questionnaire is discussed in this paper.

Aged↗

Mass screening for neuroblastoma in Miyagi Prefecture.

In Japan, aiming at early and preclinical detection of neuroblastoma in infancy a mass screening program for the tumor has been implemented nationwide using urinary tests for catecholamine metabolites, vanillylmandelic acid (VMA) and homovanillic acid (HVA) (Sawada 1990; Sawada et al. 1991). In this report, the results obtained from the screening program in Miyagi Prefecture for the last 6 years are described. The detection rate of neuroblastoma by mass screening was 1:8,377 among 125,652 infants tested in Miyagi Prefecture. All but one patients survived after removal of the primary tumor and none or minimal chemotherapy.

Biomarkers, Tumor↗

Correlation of prostate-specific antigen before prostate cancer detection and clinicopathologic features: evaluation of mass screening populations.

OBJECTIVES: Although prostate-specific antigen (PSA) has become the reference standard for prostate cancer diagnosis, few reports have examined the long-term changes in PSA values before the diagnosis of prostate cancer in a large number of subjects. We investigated serial PSA levels and related values before prostate cancer diagnosis in a mass screening population and analyzed the values in an attempt to discover some values useful in clinical diagnostic science. METHODS: We performed mass screening for prostate cancer in 9671 subjects from 1986 to 1998. The initial screening method was measurement of prostatic acid phosphatase from 1986 to 1991 and measurement of PSA from 1992 to 1998. As a result, 303 cases of prostate cancer were diagnosed. For all the cases diagnosed before 1991, we measured the serum PSA value in preserved frozen serum. RESULTS: The prostate cancer detection rate was 3.1% among all subjects observed during the 13-year period. By measurement of the PSA level using frozen serum during the pre-PSA era, we found that 62% of patients demonstrated a PSA abnormality for more than 1 year (average 2.8) before prostate cancer diagnosis. Prostate cancer that was diagnosed within 1 year after a PSA value became abnormal was not associated with bone metastasis. Concerning the relationship between PSA velocity (PSAV) and clinical stage, the proportion of Stage B cancer was 86% in the subjects whose PSAV level before diagnosis was 0.18 ng/mL/yr or less and it was only 29% in those with PSAV levels of 4.5 ng/mL/yr or more. Only 3 (3.5%) of 86 patients with prostate cancer with PSAV levels of 4.4 ng/mL/yr or less had bone metastasis, and 2 of those 3 patients had poorly differentiated adenocarcinoma. CONCLUSIONS: Although a total of 62% of patients had an abnormal PSA level more than 1 year before prostate cancer diagnosis, no patients with prostate cancer who were diagnosed within 1 year after the PSA level became abnormal had bone metastasis. Among patients who have undergone mass screening twice or more, a clinically useful indicator of the lack of bone metastasis would be a period between the detection of PSA levels of 4.1 ng/mL or more but not more than 10 ng/mL and prostate cancer diagnosis of less than 1 year and a diagnosis of well or moderately differentiated adenocarcinoma or a PSAV of 4.4 ng/mL/yr or less and a cancer diagnosis of well or moderately differentiated adenocarcinoma.

Adult↗

Persistence and possible progression of a pelvic neuroblastoma detected by mass screening during 19 months.

PURPOSE: The preclinical detection of neuroblastoma by screening for elevated levels of urinary catecholamines often leads to the discovery of children with early-stage, biologically favorable disease. It is uncertain how vigorously therapy must be pursued in such cases. We report an infant whose pelvic mass was initially thought to be a fecaloma, and consequently was not treated for 19 months. CASE REPORT: A 2-month-old girl was referred for evaluation for the presence of a neuroblastoma because of elevated urinary catecholamines detected in a mass screening program. Although no mass was initially found, urinary catecholamines became increasingly elevated, and a pelvic mass was finally radiologically identified. It was resected. Histology showed it to be a neuroblastoma, POG stage C, International stage 3, with unfavorable Shimada features, although near triploid with an unamplified N-myc oncogene. Chemotherapy was given for five cycles, and the child remains well, with no evidence of disease. CONCLUSION: Although mass screening programs often detect early- stage, biologically favorable neuroblastomas that may spontaneously regress, our case had rising levels of urinary catecholamines and unfavorable histologic features at the time of resection. The unusual location of the tumor, and radiologic features of a fecaloma, contributed to the delay in definitive diagnosis, although persistence of elevated urinary catecholamines in the absence of a tumor is infrequent.

Catecholamines↗

The usefulness of gastric mass screening using serum pepsinogen levels compared with photofluorography.

Chronic atrophic gastritis, which is though to be a high risk for gastric cancer, can be diagnosed by serum pepsinogen levels. We compared the usefulness of the measurement of pepsinogen levels and indirect photofluorography as indicators of gastric cancer in a mass screening involving 5,620 Japanese subjects (mean age: 60.1 years old; male : female = 2,268:3,352) in 1991 and 1992. Subjects with a serum pepsinogen I level below 30 micrograms/liter or a pepsinogen I/II ratio below 2.0 were considered to be at high risk of gastric cancer. The incidence of gastric cancer and the ratio of early cancers detected by pepsinogen levels (0.12%, 4/7) were similar to those detected by photofluorography (0.11%, 4/6). Our results showed that mass screening using pepsinogen levels was as useful as indirect photofluorography for the detection of gastric cancer in Japan. In addition, our results showed that the sensitivity of gastric mass screening was increased when the measurement of serum pepsinogen levels was combined with photofluorography.

Female↗

The use of Phadiatop in mass-screening programmes of inhalant allergies: advantages and limitations.

The validity of Phadiatop as a tool in the mass screening for inhalant allergies was investigated. Seventy-nine out of 600 recruits (13.2%) were classified as allergic to inhalant allergens (68 oculorhinitis; 11 asthma) on the basis of positive history, confirmed by skin testing and/or RAST for the seven most common aero-allergens in Italy. Another 74 subjects had positive RAST and/or skin tests, yet had never experienced allergic symptoms. Phadiatop was positive in 145/600: in 78 out of 79 allergics and in 67 RAST-positive non-allergics. Correlation between Phadiatop and RAST was statistically significant, though higher for grass pollens (r = 0.85, P less than 0.001) than for Dermatophagoides pteronyssinus (r = 0.68, P less than 0.01). PRIST (cut-off 220 IU/ml) identified 36/79 allergics (45.6% sensitivity, whereas that of Phadiatop was 98.7%). As the high percentage of cases in the unselected population had specific serum IgE against inhalant allergens and no allergic symptomatology, the Phadiatop-positive predictive value falls to 53.7%, thus creating the need for Phadiatop-positive subjects to undergo further investigation for an appropriate diagnosis. Given this limitation, Phadiatop appears to be an important step forward in the field of mass-screening programmes for inhalant allergies.

Adolescent↗