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PubMed1990

Fluorescent probes for cancer detection.

Several new fluorescent dyes, derivatives of pyrene and of coumarin, were synthesized that have excitation and emission wavelength maxima considerably red-shifted as compared to most pyrene and coumarin compounds. These new fluorescent compounds have high extinction coefficients and high quantum yields, and they also are very environmentally sensitive, which makes them good probes of biological systems. Several of these fluorescent compounds are preferentially taken up and retained by leukemic and other cancer tissue cell lines as compared to normals, particularly 1,3-dihydroxy 6,8-pyrenedisodiumsulfonate and 3-(carboxymethylester)-7-julolidinocoumarin. These compounds may have some usefulness in cancer detection.

Evaluation Studies as Topic↗
PubMed2004

Computer-aided detection output on 172 subtle findings on normal mammograms previously obtained in women with breast cancer detected at follow-up screening mammography.

PURPOSE: To evaluate, by using a computer-aided detection (CAD) program, the nonspecific findings on normal screening mammograms obtained in women in whom breast cancer was later detected at follow-up screening mammography. MATERIALS AND METHODS: Four hundred ninety-three mammogram pairs-an initial negative screening mammogram and a subsequently obtained screening mammogram showing cancer-were collected. The mean interval between examinations was 14.6 months. In 169 cases, in which 172 cancers were later depicted, findings on the initial mammogram were subtle enough that either none or only one or two of five blinded radiologists recommended screening recall. On the initial negative mammograms, of the 172 areas where cancer later developed, 137 (80%) had subtle nonspecific findings and were retrospectively judged as having a benign or normal appearance. The mammograms with these subtle findings were evaluated with a commercially available CAD program, and the numbers of CAD marks on these nonspecific findings were analyzed. RESULTS: Of the 172 cancers, 129 (75%) were invasive and 43 (25%) were ductal carcinoma in situ. The CAD program marked 72 (42%) of the 172 findings that subsequently developed into cancer: 24 (29%) of 82 findings recalled by none, 25 (49%) of 51 findings recalled by one, and 23 (59%) of 39 findings recalled by two of the five radiologists. Among the 137 areas with nonspecific normal or benign findings, 41 (30%) areas where cancer subsequently developed were marked by the CAD program. CONCLUSION: A subset of cancers have perceptible but nonspecific mammographic findings that may be marked by a CAD program, even when the findings do not warrant recall as judged at blinded and unblinded radiologist review. The authors believe failure to act on such nonspecific but CAD-marked findings prospectively does not constitute interpretation below a reasonable standard of care.

Adult↗
PubMed1970

Is screening for cancer worth while? Results from a well-woman clinic for cancer detection.

1,768 women were screened for breast and cervical cancer in the year May 1968 to April 1969. Clinical examination followed the completion of a simple questionary. Investigations included thermography and mammography of the breast and cytology of the cervical and vaginal smears. Breast cancer was detected in 15 patients (0.85% or 8.5 per 1,000) and none was aware of any abnormality though 13 of the tumours were clinically palpable. Carcinoma in situ of the cervix was found in a further eight (0.45% or 4.5 per 1,000).

Breast Neoplasms↗
PubMed2000

Twelve prostate biopsies detect significant cancer volumes (> 0.5 mL).

OBJECTIVES: To compare, in a retrospective study, pathological specimens of prostate cancer detected in additional areas of a 12-core biopsy with tumours detected using traditional sextant biopsy. PATIENTS AND METHODS: The study included 27 patients who had undergone radical prostatectomy (RP) for prostate cancer. Prostatectomy specimens of cancers detected using standard sextant biopsies were compared with those detected using six additional core biopsies. The RP specimens were analysed for cancer volume, Gleason score, tumour grade (Mostofi) and pathological stage. RESULTS: Of the 27 patients, six (29%) had cancer detected in the extra six biopsy cores which would have otherwise have been undetected using sextant biopsy. Only two insignificant cancers were detected. The mean Gleason score was 6.1 for cancer detected by the sextant or 12-core method (P = 0.907); the mean grade (Mostofi) was 2.1 and 2. 33, respectively (P = 0.29). The final tumour stage in the 21 patients undergoing sextant biopsy was pT2 in 13 and pT3 in eight, compared with six pT2 tumours in the six patients diagnosed using extra biopsies. The mean (median, range) tumour volume was 5.7 (3.5, 0.312-23.75) mL for cancers detected on sextant biopsy and 1.99 (1. 85, 0.4-3.6) mL in the six cancers detected using extra cores (P = 0. 0138). CONCLUSION: The detection of prostate cancer was increased using extra biopsy cores. There was a significant difference in tumour volume but not in Gleason score, Mostofi grade or final pathological tumour stage between tumours diagnosed using 12 cores and those detected on sextant biopsy.

Aged↗
PubMed1994

The mathematical basis for the increased sensitivity in cancer detection in air-dried cytopreparations.

It is known that the volume of a sphere is 4/3 pi r3, the area of a circle is pi r2, and the nuclear volume remains constant even when a cell is flattened. The effect of air-drying that flattens a spherical nucleus with a radius of r to a discoid nucleus with an expanded radius of R and a thickness of T can be stated as follows: pi R2 = (4/3 pi r3)/T. Based on this formula, a graph was plotted to illustrate the effect of air-drying on the observed nuclear areas (ONA) of cells of various size. The ONA of ethanol-fixed Pap/H&E-stained cells or cells in tissue sections is pi r2; the ONA of air-dried Diff-Quik-stained cells is pi R (2), i.e., (4/3 pi r3)/T. The former follows a first-order straight line, and the latter follows a second-order curve. As a consequence, the subtle "nuclear size enlargement" and "broader nuclear size distribution" of low-grade cancer cells, detectable only by statistical analysis of the data obtained by an image analyzer in ethanol-fixed cytopreparations or in formaldehyde-fixed tissue sections, become augmented to such a degree on the air-dried Diff-Quik-stained preparations that they are easily detected by direct microscopic observation. In conclusion, the increased sensitivity in cancer detection in air-dried cytopreparations is due to the fact that the ONA of air-dried cells reflects nuclear volume.

Cell Nucleus↗
PubMed1994

The American Cancer Society's National Prostate Cancer Detection Project.

As a significant public health problem, prostate cancer meets nearly all the criteria for screening. While concerns about incomplete natural history, progression rates and need for better prognostic factors are valid, important social and public health issues also need consideration. If future expenditures for terminal cancer care are minimized via reductions in therapy choices or coverage, no economic benefit for prostate cancer screening should exist. Narrowly focused attempts at cost reduction could inappropriately discourage highest risk groups from participating in early detection programs, thereby eliminating the greatest potential benefit of screening. The ACS-NPCDP has demonstrated that early detection of prostate cancer produced distinct stage migration to earlier, more curable disease through optimized use of DRE, TRUS and PSA. PSA is the most objective test and detects tumors of significant biologic potential. Current cost savings are possible with improved public health education about the appropriateness of early detection in the oldest age groups or those with significant pre-existing medical conditions. Prostate cancer control perhaps requires a tailored approach of screening in high risk groups and more appropriate "case finding" in the lower risk general population. The initial combination of PSA and DRE represents an ethical and economical choice for individual patients consulting with informed physicians.

Age Factors↗
PubMed2006

[Usefulness of detecting cancer procoagulant activity and thyrotropic hormone concentration in the differentiation of tumor-like changes in the thyroid].

Epidemiological studies have shown the increased incidence of malignant cancer of the thyroid gland observed in the last decade. This increase is connected with the elevated number of benign tumor-like/tuberous changes in the thyroid gland. Since it is difficult to differentiate diagnostically this pathology, it would be justified to search for biochemical markers which can help to confirm this change. The aim of our study was to evaluate the usefulness of detecting cancer procoagulant activity (CP) and thyrotropic hormone concentration (TSH) in the differentiation of tumor-like changes in the thyroid gland. The study included 15 patients (12 women and 3 men) with adenoma glandulae thyreoideae or nodular changes in the character of struma nodosa hyperplastica and 12 patients (11 women and 1 man) with carcinoma glandulae thyreoideae. A control group consisted of 12 healthy people (5 women and 7 men). CP activity was determined in the serum by the coagulation method according to Gordon and Benson and it was expressed as the coagulation time in seconds (s). TSH concentration was measured by the immunoenzymatic method (MEIA) using an analyzer of Axsym (Abbott) and was expressed in microU/ml. The results of our study indicate that the determination of CP activity can be used in the differential diagnosis of tumor-like changes of the thyroid gland. The concentration ofTSH was within the normal values, despite statistically different mean values between particular groups that results from the fact that patients qualified to surgery were in the state of euthyreosis.

Adenoma↗
PubMed2006

Application of Bayesian modeling of autologous antibody responses against ovarian tumor-associated antigens to cancer detection.

Biomarkers for early detection of epithelial ovarian cancer (EOC) are urgently needed. Patients can generate antibodies to tumor-associated antigens (TAAs). We tested multiplex detection of antibodies to candidate ovarian TAAs and statistical modeling for discrimination of sera of EOC patients and controls. Binding of serum antibody of women with EOC or healthy controls to candidate TAA-coated microspheres was assayed in parallel. A Bayesian model/variable selection approach using Markov Chain Monte Carlo computations was applied to these data, and serum CA125 values, to determine the best predictive model. The selected model was subjected to area under the receiver-operator curve (AUC) analysis. The best model generated an AUC of 0.86 [95% confidence interval (95% CI), 0.78-0.90] for discrimination between sera of EOC patients and healthy patients using antibody specific to p53, NY-CO-8, and HOXB7. Inclusion of CA125 in the model provided an AUC of 0.89 (95% CI, 0.84-0.92) compared with an AUC of 0.83 (95% CI, 0.81-0.85) using CA125 alone. However, using TAA responses alone, the model discriminated between independent sera of women with nonmalignant gynecologic conditions and those with advanced-stage or early-stage EOC with AUCs of 0.71 (95% CI, 0.67-0.76) and 0.70 (95% CI, 0.48-0.75), respectively. Serum antibody to p53 and HOXB7 is positively associated with EOC, whereas NY-CO-8-specific antibody shows negative association. Bayesian modeling of these TAA-specific serum antibody responses exhibits similar discrimination of patients with early-stage and advanced-stage EOC from women with nonmalignant gynecologic conditions and may be complementary to CA125.

Antibodies, Neoplasm↗
PubMed2002

Palpable breast thickening: role of mammography and US in cancer detection.

PURPOSE: To determine the frequency of breast carcinoma and ascertain the diagnostic yield of mammography and breast ultrasonography (US) in the detection of breast carcinoma in women with palpable breast thickening. MATERIALS AND METHODS: One hundred twenty-three consecutive cases of breast thickening (103 patients) during a 1-year period were reviewed. Experienced breast examiners prospectively identified patients with breast thickening. Results of diagnostic mammographic work-up, breast US, breast biopsy, and clinical follow-up were retrospectively reviewed. RESULTS: Six (5%) of 123 cases had a diagnosis of breast carcinoma; five (83%) of the six had invasive carcinoma. Mammography was performed in all cases, US in 77 (63%) cases. Mammographic sensitivity for invasive cancer detection was 60% (three of five cases), specificity was 94% (102 of 108 cases), and negative predictive value was 97% (102 of 105 cases). Sensitivity of US alone was 100% (two of two cases), specificity was 96% (65 of 68 cases), and negative predictive value was 100% (65 of 65 cases). The combined negative predictive value of mammography and US was 100%. Patients with prior biopsies at the site of palpable thickening accounted for most false-negative mammograms. Median time to initiate follow-up of patients in whom biopsy was not performed was 14 months. CONCLUSION: Breast cancer was discovered in 5% of women with palpable breast thickening. Women with negative mammograms and US scans are at low risk for cancer but should, in our opinion, be followed up at short-term intervals with clinical examination and imaging if biopsy is not elected by their surgeon or clinician.

Adult↗
PubMedDate not supplied

New developments in monoclonal antibodies for cancer detection and therapy.

Monoclonal antibodies have provided clinicians with an intriguing, target-specific approach to cancer management. Used alone or conjugated with drugs, toxins, or radionuclides, monoclonal antibodies have been shown to be useful in the detection and/or treatment of several cancers. Recent advances, such as the development of "humanized" antibodies, promise to increase their effectiveness even more. This article summarizes the status of the in vivo use of monoclonal antibodies for cancer detection and therapy.

Antibodies, Monoclonal↗
PubMed1986

[The statistical evaluation of the female breast cancer detected by mass screening in Hokkaido].

In Hokkaido, 113, 612 women were subjected to mass screening of breast cancer from 1973 to 1983. Out of them, 74, 285 (56.3%) were examined once and the remainder twice or more: 4,798 (4.2%) were advised to receive further precise examinations and 99.8% of them underwent the second examination. Breast cancer was detected in 377, in which 291 (77.2%) were detected by the first examination and 33 (3.8%) were so-called "interval cancer" with the mean interval of 19.3 months. The detection rate was 0.3%. Histologically non-invasive cancer was seen in 26 (6.9% of 377). Despite a recent significant increase in detection rate of the earlier stage of breast cancer, the present study showed no evidence of a decrease in advanced cancer. The prognosis of the patients who had curable operation revealed 86.9% in 5 year survival rate and 40% in 10 year survival rate.

Breast Neoplasms↗
PubMedDate not supplied

Variation in average costs among federally sponsored state-organized cancer detection programs: economies of scale?

BACKGROUND: Societal cost-effectiveness analysis and its variants help decision makers achieve an efficient allocation of resources across the set of all possible health interventions. Sometimes, however, decision makers are focused instead on the efficient allocation of resources within a particular intervention program that has already been implemented. This is especially true when the intervention is being delivered at several different sites. An analysis of average cost across program sites may help program officials to maximize the health benefits that can be achieved with limited resources. In this article, the authors present such an analysis, with special attention paid to the possible existence and implications of economies of scale. METHODS: Focusing on federally sponsored, state-organized cancer detection programs, the authors modeled 19 state programs as productive processes and examined their average costs over a 2- to 5-year period of operation. They considered 3 alternative definitions of output: women served, screens performed, and conditions detected. Average federal costs and average total costs were estimated for each grant period. Multivariate regression analysis was used to help explain the variation in average costs. RESULTS: The average cost estimates were distributed in a skewed pattern with the majority of observations falling close to the median and substantially below the mean. For all measures considered, average cost decreased as output expanded. This inverse relationship between average cost and output level persisted even after controlling for the effects of other predictors, suggesting the possible existence of economies of scale. DISCUSSION: The potential existence of economies of scale calls into question the assumption of a constant average cost frequently made in economic analyses of proposed public health programs. It also implies that a) differences in output level should be taken into account when comparing operating efficiency across program sites; b) conclusions from societal cost-effectiveness analyses may depend on the level of output at which the programs are evaluated; c) cost projections could be inaccurate if they do not take into account the decrease in average cost that occurs as output expands; and d) gains might be possible if similar programs with limited output potential are integrated, perhaps through cost sharing.

Breast Neoplasms↗
PubMed2004

Risk for distant recurrence of breast cancer detected by mammography screening or other methods.

CONTEXT: Selection of systemic adjuvant therapies for women diagnosed as having breast cancer is based on risk estimations for cancer recurrence. In such estimations, tumors detected by mammography screening are considered to be associated with a similar risk of recurrence as tumors of similar size found by other methods. OBJECTIVE: To compare the risk of recurrence and survival among women with cancerous tumors detected by mammography screening compared with other methods (outside of screening). DESIGN, SETTING, AND PATIENTS: Retrospective study comparing clinical, histopathological, and biological features of cancerous tumors detected by mammography screening compared with tumors detected outside of screening. Women diagnosed as having breast cancer in 1991 or 1992 were identified from the Finnish Cancer Registry (n = 2842). The median follow-up time was 9.5 years. Cancer biological variables were analyzed from tumor tissue microarrays using immunohistochemistry or in situ hybridization and included ERBB2, TP53, and MK167 expression and ERBB2 amplification data. MAIN OUTCOME MEASURES: Univariate and multivariate analyses of potential risk factors for distant recurrence of breast cancer and 10-year survival. RESULTS: Of the 1983 women with unilateral invasive breast cancer, data on tumor diameter were available for 1918 women. Women with cancerous tumors detected by mammography screening had better estimated 10-year distant disease-free survival than women with tumors found outside of screening (tumor size of < or =10 mm [n = 386] 92% vs 85% [P =.04]; 11-20 mm [n = 808] 88% vs 76% [P<.001]; 21-30 mm [n = 409] 86% vs 63% [P =.008]; >30 mm [n = 315] 68% vs 50% [P =.12], respectively). In a Cox multivariate model that included cancer biological factors, the relative hazard ratio for distant recurrence among women with tumors detected outside of screening (HR, 1.90; 95% confidence interval, 1.15-3.11) was significantly higher than among women with tumors detected by mammography screening (P =.01). Breast cancer diagnosis by mammography screening was an independent prognostic variable reducing the relative HR for distant recurrence. This effect was equal to or greater than the effect of 1-cm decrease in tumor diameter (HR, 1.20; 95% confidence interval, 1.10-1.31). CONCLUSIONS: Cancerous tumors detected by mammography screening are associated with a better prognosis than tumors of similar size found outside of screening. The risk of distant metastases is overestimated for women diagnosed as having cancer by mammography screening unless the method of detection is taken into account in risk estimations.

Adult↗
PubMed2005

[Evaluation of prostate specific antigen (PSA) adjusted to transition zone in prostatic cancer detection].

OBJECTIVE: To investigate if PSA adjusted to transition zone (PSA-TZ) can be considered as a predictor parameter of cancer with better specificity or not than PSA, PSA density (PSAD) or PSA free/total ratio. MATERIAL AND METHODS: Data of 706 patients with sextant prostatic biopsies are analyzed in prospective way because of prostatic cancer suspicion. Range of PSA was between 4 to 20 ng/ml. Determination of PSA-TZ was calculated by dividing the PSA value by the volume of the transition zone of the prostate applying the ellipsoid formula and comparison of obtained results in detection of cancer was performed by ROC curves analysis for each one of PSA-related parameters. RESULTS: Of the total group of patients, in 199 cases (28.2%) prostatic cancer was detected. Analysis by ROC curves demonstrated than PSA-TZ and PSAD were better predictors of cancer than PSA free/total ratio and PSA (p < 0.0001). The cutoff value of PSA-TZ of 0.18 ng/ml/cc was considered as the best, obtaining a 95% sensitivity and a 27% specificity. For this sensitivity, PSA, PSAD and PSA free/total ratio only obtained 5, 9 and 16% specificity respectively. Areas under curve (AUC) obtained for PSA, PSA free/total ratio, PSAD and PSA-TZ were 0.539, 0.612, 0.694 and 0.722 respectively. CONCLUSIONS: PSA-TZ in the studied population was a parameter with better diagnostic specificity than PSA, PSAD and PSA free/total ratio for the same 95% sensitivity. This would justify its utility in clinical paractice reducing the number of unnecesary biopsies.

Aged↗
PubMed1981

Breast cancer detection utilizing biostereometric analysis.

Twelve female patients participated in a study designed to employ computer-assisted biostereometric analysis for the detection of breast masses. All breast masses were previously documented by physical examination and followed by xeromammography, stereophotography, and histopathologic confirmation of tumor type. "Contour mammograms" were produced from the biostereometric photographs. These data were analyzed first for tumor detection and location by visual inspection. A second analysis employed a computed algorithm designed to locate and measure surface aberrations that suggest the possibility of underlying breast tumor. Visual analysis yielded the exact location of breast tumors in eight of the ten malignancies; computer analysis exactly located nine of the ten malignancies. In the computer analysis, one malignancy not exactly located by quadrant was, nevertheless, located in the correct breast. The results of the study suggest that the biostereometric process may have future use in screening or prescreening procedures for breast cancer detection. It is noninvasive, applicable to large numbers of women and with suitable refinements, and capable of being fully automated.

Aged↗
PubMedDate not supplied

Synthesis and application of a water-soluble near-infrared dye for cancer detection using optical imaging.

A novel water-soluble 2-[2-(2-chloro-3-{2-[3,3-dimethyl-5-sulfo-1-(4-sulfo-butyl)-3H-indol-2-yl]-vinyl}-cyclohex-2-enylidene)-ethylidene]-3,3-dimethyl-1-(4-sulfo-butyl)-2,3-dihydro-1H-indole-5-carboxylic acid (dye 2) was developed via an asymmetric approach. With an additional sulfonate group, the near-infrared feature of this dye exhibited a 2-fold increase in quantum yield compared to the previous generation. The current synthetic strategy provided a single carboxylic group as a handle for conjugation, thus allowing selectivity for bioconjugation. The stability of this dye was demonstrated by labeling peptides via solid-phase peptide chemistry. The in vivo optical imaging showed potential and broad applications of this dye in developing molecular-based beacons for cancer detection.

Animals↗
PubMed1999

p53 gene mutations in non-small cell lung cancer detected by polymerase chain reaction single-strand conformation polymorphism analysis.

Mutations of the p53 tumor suppressor gene are the most frequent genetic alterations detected in human lung cancer. To assess the pathogenic significance of p53 gene alterations in Chinese non-small cell lung cancer (NSCLC), 74 paired samples of primary lung cancer and normal lung tissue far away from the cancer were analyzed for mutations of the p53 gene (exons 5-8) using exon-specific PCR, single-strand conformation polymorphism (PCR-SSCP). p53 mutations were observed in 55.4% (41/74) of the samples. No linkages were detected between the incidence of p53 mutations and histological type, lymph node metastasis, age or sex. Significant association between p53 mutations and degree of differentiation in adenocarcinomas, not in squamous cell carcinomas, was observed. The frequency of p53 mutations in smokers (65.3%) was higher than in nonsmokers (33.3%) and reached statistical significance. We also found p53 mutations in 6/7 samples which had tissue invasion and distant metastasis. These results suggest that smoking could be an important factor in lung carcinogenesis, p53 mutation is a worse prognosis indicator in adenocarcinomas and related to high aggressive behavior of human lung cancer.

Adenocarcinoma↗
PubMed2003

Breast cancer detection in gadolinium-enhanced MR images by static region descriptors and neural networks.

PURPOSE: To automate the diagnosis of malignancy by classifying breast tissues as negative or positive for malignancy in gadolinium-enhanced dynamic magnetic resonance (MR) images, using static region descriptors and a neural network classifier. MATERIALS AND METHODS: We propose a novel approach whereby the classifier evaluates a number of parameters that identify important tumor characteristics, as obtained by digital image processing techniques. These parameters include static signal intensity (SI) after contrast enhancement, mass margin descriptors, evaluation of mass shape by calculation of eccentricity, mass size, and mass granularity by texture analysis. Datasets for 14 patients were obtained by use of the 1.5T PMRTOW Clinical Imager. RESULTS: Statistical performance evaluation of the neural networks indicated 90%-100% sensitivity, 91%-100% specificity, and 91%-100% accuracy. CONCLUSION: Although this work is preliminary, it may reduce overall health-care time and costs, and enable higher accuracy in automated breast cancer detection systems.

Breast Neoplasms↗