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Observer variability in cancer detection during routine repeat (incident) mammographic screening in a study of two versus one view mammography.

OBJECTIVE: To examine the reasons for observer variability of cancer detection using one and two view mammography at incident (subsequent) screening and determine whether false negative results (non-recall of a cancer) are due to failure to detect the associated features(s) of the cancer on the mammogram, or misinterpretation of the observed feature(s) as not indicative of malignancy. SETTING: A random selection of cancers (invasive and in situ) seen as incident cases during the second screening round (January 1994-January 1997) in the South West London Breast Screening Service were used. This service uses two view mammography and double reading with arbitration by a third or further readers for all screens. METHODS: Mammograms of cases were mixed with those of controls in a 1:2 ratio in two test sets. Eleven experienced film readers, each reading both test sets, took part in the study. Initially the oblique view only was read, then, additionally, the craniocaudal view. Previous films were available to the readers. Data on abnormalities noted on the films and probability of recall were recorded and analysed. RESULTS: 387 valid readings of 36 cancers (30 invasive and six ductal carcinoma in situ) were made by 11 readers. The overall sensitivity increased from 79% with one view to 85% with two views. For invasive cancers < 10 mm the sensitivity was 71% with one view, but increased to 85% with two views. Recall of individual cancers by the readers varied substantially. With one view 15 (50%) of the 30 invasive cancers were recalled by all 11 readers, increasing to 18 (60%) with two views. Of the invasive cancers not recalled by all 11 readers, there was considerable disagreement, particularly for the smaller cancers. With one view 69% of invasive cancers < 10 mm were correctly marked on the proforma compared with 87% with two views. Invasive cancers > 10 mm were almost all marked on the proforma with one or two views. For invasive cancers, the misinterpreted feature that did not lead to recall was most commonly an asymmetry (42%), whereas for in situ cancers it was calcifications (67%). The finding of an irregular mass was the least misinterpreted feature. CONCLUSION: The study showed that of those invasive cancers detected at routine repeat screening by a programme using two view mammography and double reading with arbitration, at least 50% could be described as "difficult" (for example, "minimal" signs) to recall using the single reading of one view, even under "favourable" study conditions with two normal subjects per case. The finding that at least 87% of invasive cancers < 10 mm are detected (marked on the proforma) with two views, but only 69% with the one view, suggests that for single reading of mammograms with one view the detection of small invasive cancers is a major problem. This problem is helped by the second view. For invasive cancers > or = 10 mm, interpretation (benign or malignant) rather than detection (under these study conditions) was the major cause of recall failure. The most common signs to be misinterpreted were calcifications and asymmetries; once visualised an irregular mass was least likely to be misinterpreted. This study provides evidence that detection and interpretation of most invasive cancers is improved by increasing the number of views, and by increasing the number of readers.

Breast Neoplasms↗

Cancers detected and induced in mammographic screening: new screening schedules and younger women with family history.

The numbers of cancers detected and induced in breast screening programmes are examined for two-view screening, and for a 2 year screening interval, in contrast to the single view screening at a 3 year interval of the UK Breast Screening Programme up until early 1995. Two-view screening is also considered for the 1 year interval and age range of the current UK age trial (40-47 years). The corresponding figures for screening of groups having a family history of breast cancer are calculated and discussed. Breast cancer induction data are taken from National Radiological Protection Board publications. Cancer detection rates are based on observed rates where available, and calculated rates otherwise. The results of calculations indicate cause for concern if screening is to be extended below the age of 30 years (or below 35 years in certain categories), or below 40 years of age if family history groups are shown in the future to have a generally increased susceptibility to ionizing radiation. The importance of restricting dose to 2 mGy per film (mean glandular dose for a standard breast thickness of 4.5 cm) is stressed, together with the need ot maintain maximum image quality. This is especially true for the family history groups, who should only be screened in centres within established screening programmes, or in centres with equally strict quality control procedures.

Adult↗

Review of complex breast cysts: implications for cancer detection and clinical practice.

The use of ultrasound in breast diagnosis has resulted in the increasing identification of incidental benign-appearing lesions, of which complex (or atypical) breast cysts are frequently reported. Complex breast cysts were estimated to be reported in approximately 5% of breast ultrasound examinations. A systematic review of the literature on sonographically detected complex breast cysts was carried out. The quality of primary studies and extracted data on cancer detection was assessed. Very few studies have examined complex breast cysts and quantified the associated cancer detection rate. In most of these studies, subjects have been selected on the basis of progress to intervention, which would overestimate the likelihood of malignancy. The only study to examine complex cysts from all consecutive ultrasounds reported one case of non-invasive cancer from 308 lesions--0.3% (95% confidence interval, 0.01-1.84). Ultrasound features associated with a higher risk of the lesion being a cancer are: thickened walls, thick internal septations, a mix of cystic and solid components, and an imaging classification of indeterminate. Using the information from the present review, complex breast cysts were categorized on the basis of associated risk of malignancy, and an approach to the management of these lesions to assist clinical decision-making was suggested. Provided adequate information is given to the patient, complex breast cysts with a very low risk of malignancy do not always require image-guided biopsy.

Algorithms↗

Nonpalpable mammographically occult invasive breast cancers detected by MRI.

OBJECTIVE: The purpose of this study was to determine the MRI findings and histology of clinically and mammographically occult invasive breast cancers detected by MRI. MATERIALS AND METHODS: A retrospective review was undertaken of 1,336 breast MRI examinations performed during a 2-year period. Among these, 68 nonpalpable mammographically occult invasive cancers were identified in 57 women with a median age of 50 years (range, 30-72 years). MRI findings were classified according to the breast MRI lexicon. Medical records were reviewed to determine the histology. RESULTS: Indications for performing MRI were extent of disease assessment in 72% (41/57), high-risk screening in 25% (14/57), and problem solving in 3% (2/57). MRI lesion types in these 68 invasive cancers were nonmass in 57% (39/68) and mass in 43% (29/68). Kinetics were plateau in 59% (40/68), washout in 38% (26/68), and persistent in 3% (2/68). Histology was invasive ductal cancer in 65% (44/68), mixed invasive ductal and lobular cancer in 19% (13/68), and invasive lobular cancer in 16% (11/68). The cancer stage was I in 61% (34/56), II in 32% (18/56), and more advanced in 7% (4/56). Sixty-three percent (43/68) of lesions were minimal cancers, defined as invasive cancers measuring under 1 cm. CONCLUSION: In this study of mammographically and clinically occult cancers detected by MRI, 57% (39/68) of invasive breast cancers were evident as nonmass enhancement, and 63% were minimal breast cancers.

Adult↗

The Breast Cancer Detection Demonstration Project 25 years later.

The Breast Cancer Detection Demonstration Project was initiated 25 years ago to demonstrate the feasibility of large-scale screening for breast cancer. A retrospective view shows that it has more than fulfilled its mission; among other important accomplishments it has significantly advanced both the notion and science of population-based breast cancer screening and provided a huge data base for epidemiologic research.

Adult↗

Cancer detection in working women: a report on 7450 subjects.

A cancer detection programme for women was devised in 1964 by the writer, who attended an increasing number of work centres, mostly on an annual basis. During 12 years 7450 women were examined, some of them more than once. There were 237 abnormal Papanicolaou smears (in 112 of which the histological diagnosis was carcinoma or moderate to severe dysplasia), and 18 carcinomas of the breast. Education about cancer, teaching of breast self-examination and general counseling were also carried out. The high detection rate of cancer emphasizes the need for such services to be taken to the women at risk, and suggests that annual Papanicolaou smears are still the ideal.

Adolescent↗

Colorectal cancer detection and screening.

Colon cancer is a leading cause of death in the United States and is estimated to cause 56,500 deaths during 1998. Most cancers evolve from adenomatous polyps. Screening asymptomatic average-risk individuals is recommended to reduce colorectal cancer mortality by detection and removal of adenomatous polyps.

Algorithms↗

An analysis of survival differences between clinically and screen-detected cancer patients.

Survival differences between clinically and screen-detected cancer patients partly result from biases. Well known are lead-time, length bias and overdiagnosis. The survival of the clinically detected patients in the study group of the HIP breast cancer screening project is corrected for these biases. The resulting survival curve is only slightly worse than the survival of the screen-detected patients. This suggests a very modest mortality reduction by screening. A much larger reduction is obtained from an analysis of the complete HIP results, including those of the control group. It is concluded that a large unexpected selection bias is present. This bias would not have been detected if the HIP study had not contained a randomized control group. A misleading and pessimistic conclusion on the effectiveness of breast cancer screening would thus have resulted. This conclusion reinforces the need for randomized studies.

Breast Neoplasms↗

Evaluation of transition zone and lateral sextant biopsies for prostate cancer detection after initial sextant biopsy.

OBJECTIVES: To assess the value of transition zone and lateral sextant biopsies for the detection of prostate cancer after a previous sextant biopsy was negative. METHODS: A total of 74 prostates after radical prostatectomy were used to perform biopsies ex vivo. First, a sextant biopsy was taken, then two different rebiopsy techniques were performed. Rebiopsy technique A consisted of a laterally placed sextant biopsy and two cores per side of the transition zones only. Rebiopsy technique B included a standard sextant biopsy and two cores per side from the lateral areas of the prostate. The biopsies were taken using ultrasound guidance to sample the areas of interest precisely. RESULTS: The initial sextant biopsy found 39 prostate cancers. Rebiopsy technique A found 12 cancers (34%). In this group, a laterally placed sextant biopsy found 12 cancers; transition zone biopsies revealed cancer in 5 cases, but no additional tumor was found. Rebiopsy technique B detected 23 prostate cancers (66%). Fourteen tumors were found after a second standard sextant biopsy, and nine additional tumors were found in the lateral areas. CONCLUSIONS: Sextant biopsy has a low sensitivity of only 53%. A biopsy including the transition zones is not the ideal technique for detecting the remaining tumors. Therefore, transition zone biopsies should be reserved for patients with multiple previous negative biopsies of the peripheral zone. A subsequent sextant biopsy with additional cores from the lateral areas of the prostate is favorable if rebiopsy is necessary after a negative sextant biopsy.

Biopsy, Needle↗

Planning of a screening programme for cervical cancer in Liguria and evaluation of the attitude of the female population towards cancer detection.

In 1990 an investigation aimed at evaluating the possibility of organizing a regional screening programme for the early detection of cervical cancer was carried out in Liguria. Information on resources available for early detection of cervical cancer was obtained from 12 of 20 Public Health Units; a screening programme was feasible in 8 of them. The number of Pap tests examined was evaluated for 6 of 20 cytology laboratories. Only one laboratory examined more than 20,000 Pap tests in 1989 and, according to the international guidelines, can be a referring centre for screening. However, no information was available concerning inter- and intralaboratory quality control programmes. In the same period a population-based survey was carried out using a self-administered questionnaire in order to evaluate the attitudes of women towards cervical cancer prevention. A total of 1,454 of 4,197 women (35%) participated in the study. Younger, well educated women employed in non non-manual work were more likely to participate in the study. About 65% of the respondents had satisfactory practices with regards to the Pap test, suggesting a strong self-selection that probably resulted in a sample of women more health-conscious than the general population. In conclusion, our results suggest that major interventions should be carried out in the Public Health Units to direct resources to the needs of the population. In addition, new educational methods should be adopted to reach selected population groups to encourage them to have a Pap test performed on a regular basis.

Adult↗

Survival rates for breast cancers detected in a community service screening mammogram program.

BACKGROUND: This single-institution long-term prospective study was performed in the setting of community service screening mammography to evaluate the association between the methods of breast cancer detection and survival rates. METHODS: From 1994 through 2001, data on 1237 patients with breast cancer were collected concurrent with definitive surgical treatment and entered into a comprehensive database. RESULTS: Mammography was the sole method of detection for 517 (44%) of 1179 Tis-T2 breast cancers. Fifty-seven percent of invasive cancers detectable by mammography alone were less than 1 cm in diameter. For 1049 patients with invasive cancers, the 5-year overall observed survival rates were 94% for 372 whose cancers were detectable by mammogram alone and 87% for 677 whose cancers were detectable by palpation (alone or in combination with mammography) (P = .0002). CONCLUSIONS: Most of the contribution to breast cancer mortality reduction is from the detection of small nonpalpable cancers, not from adjuvant therapy.

Breast Neoplasms↗

Transillumination in breast cancer detection: screening failures and potential.

This prospective study of 1265 women referred to a multimodality breast diagnostic center compares the sensitivity for breast cancer detection of state-of-the-art transillumination light scanning and film-screen mammography. Of 33 biopsy-proven cancers, transillumination light scanning detected 58%, while mammography detected 97% of the cancers. Light scanning did detect 55% of the nonpalpable breast cancers, and 30% of those tumors smaller than 1 cm. Detection of breast cancer by light scanning was affected by breast size, but not architecture, and was directly related to tumor size. Although transillumination light scanning can detect some small curable breast cancers (smaller than 1 cm), it does not do so at a sensitivity adequate for screening. An example is illustrated in which light scanning detected an occult breast cancer before the development of recognizable mammographic changes.

Adult↗

[Characteristics of gastric cancer detected by mass survey. Comparison with those of outpatients].

The characteristics of gastric cancers detected by mass survey were studied by comparison with those of outpatients attending our hospital. Form 1966 to 1985, a total of 290,987 examinees were screened by gastric mass survey at our Mass Survey Center. Among them, 474 cases (0.16%) of gastric cancer were detected, and of these, 254 cases (52%) were early gastric cancer. Upon comparison of macroscopic types of surgically treated cancers, there were 152 cases (39.6%) out of 784 cases in the mass survey group and 658 cases (21.3%) out of 3,091 cases in the outpatient group having the depressed type and 11% in the former and 5.5% in the latter having the elevated type of early gastric cancer. As for the prognosis of cancers in both groups, the 5- and 10-year survival rates of 274 cases in the mass survey group and 1,859 cases in the outpatient group undergoing resection between 1964 and 1974 were compared. It was found that 80.0% for 5 years and 78.5% for 10 years in relative survival rates were obtained in the mass survey group, and 56.2% for 5 years and 55.1% for 10 years in the outpatient group. This difference in survival rate was due to the fact that the mass survey group had a high ratio of early gastric cancer than the outpatient group, and that even the advanced serosal cancer former group had less lymph node metastasis than the latter group.

Ambulatory Care↗

Effects of systematic 12-core biopsy on the performance of percent free prostate specific antigen for prostate cancer detection.

PURPOSE: The performance characteristics of percent free (f) prostate specific antigen (PSA) for differentiating between benign prostatic hyperplasia and prostate cancer were originally established using primarily sextant biopsy. We determined whether the addition of 6 laterally directed cores to the traditional sextant prostate biopsy affects the performance of percent fPSA. MATERIALS AND METHODS: We retrospectively evaluated a cohort of 350 consecutive biopsies in men with negative digital rectal examinations and PSA between 4 and 10 ng/ml who underwent systematic 12 core biopsy (S12C) biopsy at Scott Department of Urology between March 1999 and January 2003. The effects of 6 additional, laterally directed biopsies on the sensitivity, specificity and area under the ROC curve for percent fPSA was evaluated in the 277 men in whom percent fPSA was measured. RESULTS: Cancers detected exclusively in the 6 laterally directed cores were associated with percent fPSA values similar to those in patients with a benign S12C biopsy. This resulted in a modest and yet predictable decrease in the sensitivity of percent fPSA at each biopsy threshold value without affecting specificity. There was a nonstatistically significant decrease in the area under the ROC curve with the addition of 6 laterally directed cores to sextant biopsy (medial sextant cores 0.66 vs S12C 0.60). CONCLUSIONS: The 12 core biopsy strategies have a higher cancer detection rate than sextant biopsies and they are gaining widespread acceptance. The addition of 6 laterally directed cores to traditional sextant biopsy may result in a modest decrease in the sensitivity of percent fPSA at each selected biopsy threshold without affecting specificity.

Aged↗

Citrate concentrations in human seminal fluid and expressed prostatic fluid determined via 1H nuclear magnetic resonance spectroscopy outperform prostate specific antigen in prostate cancer detection.

PURPOSE: We compared the performance of citrate concentration measurements in unprocessed human semen and expressed prostatic secretions from controls and from patients with biopsy confirmed prostate cancer to that of prostate specific antigen testing with respect to specificity and sensitivity for prostate cancer detection. MATERIALS AND METHODS: Semen and expressed prostatic secretions were collected in biopsy proven, prostate cancer bearing and noncancer bearing cases. Citrate concentrations were determined by quantitative in vitro, high field, water suppressed proton nuclear magnetic resonance spectroscopy. Assessments of the diagnostic performance of citrate and prostate specific antigen results in our study populations were made by ROC curve analysis. RESULTS: Citrate was measured in samples from 61 participants, of whom 16 without and 21 with cancer donated semen, and 17 without and 7 with cancer donated expressed prostatic secretions. Mean citrate +/- SE compared to that in controls was 2.7-fold lower in patients with cancer samples in semen (132.2 +/- 30.1 vs 48.0 +/- 7.9 mM, p < 0.05) and expressed prostatic secretions (221.4 +/- 55.4 vs 81.5 +/- 36.0 mM, p < 0.05). ROC curve analysis showed that measurements of citrate in semen performed as well as measurements of citrate in expressed prostatic secretion for detecting prostate cancer (AUC 0.81, 95% CI 0.60 to 0.92 and AUC 0.73, 95% CI 0.38 to 0.90, respectively, p > 0.05). ROC curve analysis also showed that the measurement of citrate in either fluid outperformed prostate specific antigen measurement for detecting prostate cancer in these subjects (AUC 0.61, 95% CI 0.44 to 0.74). CONCLUSIONS: In vitro nuclear magnetic resonance spectroscopic measurement of the citrate concentration in semen or expressed prostatic secretions outperforms prostate specific antigen testing for detecting prostate cancer.

Aged↗

Survival and mortality in a randomized study of lung cancer detection.

In a randomized prospective study of lung cancer detection in a high-risk population of over 6000 heavy smokers semiannual screening by X-ray and sputum cytology was compared to screening at a 3-year interval. The comparison of Kaplan-Meier estimates of survival curves done without and with correcting for lead-time bias disclosed a rather important impact of lead-time bias on survival comparisons. On the contrary, controlling for possible length bias had no obvious effect on the shape of survival curves. The evaluation of mortality from lung cancer, being used as a basic criterion, indicated no traceable benefit from semiannual screening. The higher incidence of lung cancer in the frequently screened group was paralleled by a higher mortality. It is concluded that currently available screening techniques will not solve the problem of lung cancer mortality in smokers. The results underline the importance of primary prevention for lung cancer.

Adult↗

Comparison of the sensitivity and specificity of the CA19-9 and carcinoembryonic antigen assays in detecting cancer of the pancreas.

In this study, we determined the sensitivity and specificity of the new serum assay CA19-9 in detecting adenocarcinoma of the pancreas and compared the results with those of the serum assay to carcinoembryonic antigen (CEA). Thirty-seven patients with biopsy-proven adenocarcinoma (14 patients with resectable disease and 23 patients with unresectable disease) were compared with 157 controls (48 patients with benign pancreatic disease, 34 patients with nonpancreatic sources of abdominal pain, 58 patients with benign jaundice, 7 patients with nonpancreatic malabsorption, and 10 patients with renal failure on dialysis). It was determined that a cutoff of 75 U/ml enhanced the diagnostic efficiency (sensitivity + specificity) of CA19-9 over the manufacturer's recommended cutoff of 37 U/ml. The sensitivity of CA19-9 (greater than 75 U/ml) in detecting cancer was greater than that of CEA (greater than 5 ng/ml) (86.5% vs. 48.4%) (p less than 0.01, McNemar test). The sensitivity of CA19-9 was 78.6% in resectable and 91.3% in unresectable disease. The specificity of CA19-9 was also greater than CEA (92.5% vs. 87.3%), although this difference was not statistically significant. The higher the CA19-9 or CEA level, the greater the specificity of either assay; at CA19-9 levels greater than 600 U/ml and CEA levels greater than 20 ng/ml the specificity is approximately 99%. The combination of an elevated CA19-9 level (greater than 75 U/ml) and an elevated CEA level (greater than 5 ng/ml) also enhanced specificity to 99%. It is concluded that CA19-9 used alone is superior to CEA used alone in detecting cancer of the pancreas and that the combination of mild elevations of both assays improves their specificity. Although the CA19-9 marker can be elevated with other intraabdominal adenocarcinomas (e.g., gastric, biliary, or colonic), CA19-9, together with CEA, will be useful to the clinician in differentiating benign from malignant pancreatic processes and in alerting the clinician to the possible presence of an intraabdominal neoplasm in the proper clinical setting.

Adenocarcinoma↗

Ratios of IGF-I, IGF binding protein-3, and prostate-specific antigen in prostate cancer detection.

Recent studies have suggested that IGF-I and IGF-binding protein (IGFBP)-3, in combination with prostate-specific antigen (PSA), may enhance prostate cancer detection. In this study, we sought to determine the effect on the prediction of future prostate cancer occurrence by incorporating ratios of total and free PSA, IGF-I, IGFBP-3 into PSA testing. Within a population-based prospective cohort study, we investigated the validity (sensitivity and specificity) of plasma concentrations of total and free PSA, IGF-I, and IGFBP-3 and combinations thereof, in 114 cases and 97 controls, in the range of 1.75-13.5 microg/l for PSA, as used by Khosravi et al. (See Ref. 7 ). Validity estimated by the area under the curve in receiver operator characteristics analysis (with 95% confidence interval) for total PSA was 0.78 (range, 0.71-0.84); total/free PSA, 0.69 (range, 0.62-0.76); total PSA/IGF-I, 0.72 (range, 0.65-0.79); free PSA/IGF-I, 0.55 (range, 0.48-0.63); total PSA/IGFBP-3, 0.74 (range, 0.68-0.81); and free PSA/IGFBP-3, 0.57 (range, 0.49-0.64). Analysis of ratios of IGF-I, IGFBP-3, and free and total PSA did not improve validity of PSA testing in the prediction of future occurrence of prostate cancer. It is unlikely that these combinations will improve prostate cancer detection.

Biomarkers, Tumor↗