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[Relation of age and prostatic volume to cancer detection in prostatic biopsies from patients with non-suspect rectal palpation].

OBJECTIVES: To evaluate which clinical variables are predictive for prostate cancer and possible relationships among them, in patients with elevated PSA and non suspicious digital rectal examination (DRE) undergoing first prostate biopsy. METHODS: 1618 patients with elevated PSA and non suspicious DRE who underwent sextant peripheral prostate biopsy were selected from our database. PSA, age, prostate volume, and detectable nodule by ultrasound were selected as variables related to cancer detection in first and second biopsies. RESULTS: Mean age was 67.5 +/- 7.4 (37-88) years, mean PSA was 16.9 +/- 116.5 (3.6-4500) ng\ml, mean prostate volume was 65.7 +/- 37.8 (8-352) cc. 23.3% patients presented a hypoechoic nodule within the peripheral zone of the gland. 18.8% presented prostate cancer on first biopsy. On multivariate analysis, age (p < 0.001), prostate volume (p < 0.001), and presence of a nodule on ultrasound (p = 0.003) were considered independent predictive variables for cancer detection on biopsy. Direct relationship with age, and inverse relationship with prostate volume were shown. Detection rates on second biopsy were greater in patients with prostates = 40 cc in comparison to those > 40 cc (p = 0.02). First two biopsies detected 95% of cancer cases, first three up to 98%. CONCLUSIONS: Age and prostate volume should be taken into consideration when individualizing the number of cores to obtain at the time of biopsy. The efficacy of peripheral sextant biopsy in prostates = for 40 cc should be re-evaluated. Third and fourth biopsies should be reserved for patients with very adverse risk factors.

Adult↗

The role of color Doppler and staging biopsies in prostate cancer detection.

OBJECTIVES: To review the current published data on the role of color Doppler sonography and sonographically-guided staging biopsies in the detection and staging of prostate cancer. This article also discusses the role of color Doppler sonography in defining the ideal patients for neoadjuvant chemotherapy. METHODS: Peer-reviewed reports in the radiologic, urologic, and medical literature were reviewed. Data from our own institution served as illustrative material. RESULTS: Color Doppler sonography using state of the art ultrasound equipment produced from the mid 1990s onward can define areas of hypervascularity in the prostate. When located in the peripheral zone and associated with definable lesions, these areas likely represent carcinoma. More importantly, when isoechoic areas contain hypervascular foci with chaotic flow, cancer is also likely. In 93% of sites that contain normal vascularity, prostate cancer was not detected by biopsy. Staging biopsies are not frequently performed in current clinical practice. A positive seminal vesicle biopsy is associated with capsular penetration in 100% and positive lymph nodes in 50% of patients with prostate cancer. CONCLUSIONS: Color Doppler sonography and staging biopsies may have a more significant role as newer alternative therapies for prostate cancer become popular. These two techniques show promise for increasing the accuracy of pretreatment staging over current algorithms, which are less than adequate.

Biopsy↗

PFK inhibition test for cancer detection: clinical applications and mechanisms of PFK inhibition.

A newly established cancer marker, the PFK inhibition test, has been further examined for its capacity to detect malignant neoplasms irrespective of the organs in which cancer cells start proliferating. We tested 1,160 sera from cancer patients and compared them with 756 normal sera, using histograms and normal paper for analysis of accumulated frequency. PFK activity through the influence of normal sera showed normal distribution, and cancerous sera shifted to the inhibitory site with an irregular shape. From these analyses, the patients were classified into the following types: normal range: PFK greater than SD (standard deviation of PFK activity in normal sera); suspicious range: SD greater than PFK greater than 2SD, must be given the PFK test again; and dangerous range: PFK less than 2SD, further examination must be carried out to detect cancer. Fifty percent of the sera from all the cancer patients inhibited PFK beyond 2 SD of normal sera. We also analyzed organ-associated PFK distribution, eg, gastric, colorectal, and mammary cancer. In gastric cancer, PFK inhibition was stronger in accordance with how far a particular stage of cancer had progressed. However, 50% of sera from stage I gastric cancer patients was positive beyond the cut-off line of 2 SD. We examined 104 sera from patients diagnosed as benign prostatic hypertrophy and found malignant cells in 10 patients whose sera tended to be positive in PFK inhibition. The PFK inhibitory factor in the body fluids of cancer patients was fractionated by Sephadex G-75 gel filtration and DEAE ion exchange chromatography. The approximate molecular weight of this factor was 13,000 daltons. The factor was resistant to heat and acid (0.1 N HCl and H2SO4) and was sensitive to 0.1 N NaOH and phosphate buffer. Diluted sulfuric acid and ammonium sulfate made an inactive NaOH-treated sample active when lyophilized following dialysis against distilled water. PFK inhibition by cancerous sera was eliminated by fructose-2,6-bisphosphate (the strongest activator of PFK) in a dose-dependent manner. PFK attached to agarose beads was found to be reversible even after being inhibited by cancerous body fluids and ATP water solution. Although PFK is apt to decay in a low pH range, the established procedure did not destroy PFK, but induced a direct inhibition of PFK by ATP through the ATP inhibition site on the PFK molecule. The PFK inhibitor may possibly function as a proton carrier and release protons to activate the ATP inhibition site.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenosine Triphosphate↗

Outcome of patients with lung cancer detected via mass screening as compared to those presenting with symptoms.

We performed lung cancer resection in 721 patients between 1980 and 1989. Cancers were detected via mass screening programs by annual chest X-ray examination in the majority of cases. We evaluated the surgical results in patients with tumors detected by mass screening and compared them to those in whom the malignancy was detected by symptoms. Lesions in the mass screened group were T1 to T2 tumors in 90% of the cases, and NO in 73%. Stage I disease accounted for 65.3% in the mass screened group. The overall 5-year survival rate was 56.2% in the mass screened group, which was significantly better than the 25.3% for the symptom group (P less than 0.001). The surgical results in the lung cancer cases detected by the mass screening program had better results than the cases who presented with symptoms.

Aged↗

Lung cancer: detection, prevention, and therapeutics.

Lung cancer remains the leading cause of cancer death in the U.S. adult population, and the American Cancer Society estimates that cigarette smoking is responsible for about 83% of all lung cancer cases. It is unlikely that significant reductions in the incidence and mortality associated with lung cancer will be realized without effective antismoking campaigns. Surgery, radiation therapy, and chemotherapy all play a role in the management of lung cancer. At the current time, NSCLC is generally curable only if it is diagnosed while the tumor is small and localized and can be surgically removed. Radiation therapy may also be effective in localized cases. Combination chemotherapy regimens have not consistently produced quality responses in patients with advanced tumors; however, newer regimens utilizing high doses of cisplatin, mitomycin and vinca alkaloids, or cisplatin and etoposide have produced encouraging results. In contrast to NSCLC, SCLC is responsive to combination chemotherapy regimens. Although many different agents are effective in this disease, most small-cell tumors eventually become refractory to chemotherapy and most patients do not survive longer than two years. Although progress has been made in the understanding and management of lung cancer, effective therapies that consistently produce major and durable responses are still lacking. Clinical trials must continue to evaluate therapeutic modalities for all types of lung cancer.

Carcinoma, Non-Small-Cell Lung↗

Bladder cancer: detection, prevention, and therapeutics.

Bladder cancer is primarily a disease of middle-aged men with a history of smoking or occupational exposure to carcinogens. Work continues on the development of effective screening methods. Prevention is the magic key in society's attempt to manage this disease. Public awareness campaigns on the hazards of smoking should include information on smoking's link to bladder cancer. Workers in high-risk industries should be made aware of the risk and practice good work habits. In industries where workers handle known bladder carcinogens, protective clothing should be worn. Yet to be determined are benefits gained by reducing the intake of coffee or artificial sweeteners.

Environmental Exposure↗

Why isn't every woman over 40 in a breast cancer detection program?

Mortality from breast cancer may be reduced by more than 10,000 deaths per year in this country if the recommendations for screening all asymptomatic women older than 40 years for breast cancer, issued in 1982 by the American Cancer Society and the American College of Radiology, are followed. Compliance with those recommendations six years later is poor, even in well-to-do, medically served populations, primarily because of poor compliance by physicians. Radiation risk is an often-cited concern, although it has been shown to be an insignificant factor in breast cancer screening. High cost, also cited as a concern, is less of a problem-the charges for mammography having declined steeply in the past few years. At the current price levels, it makes financial and humanitarian sense to provide screening rather than terminal care for metastatic breast cancer. The third concern cited by physicians, that of diagnostic accuracy, must be addressed by a careful and accurate statistical description of the results of each screening program. Sensitivity of more than 80% with positive predictive values of about a third can be achieved.

Adult↗

[Free/total ratio of prostate-specific antigen (PSA) for prostate cancer detection in patients with gray zone PSA level].

Thirty seven patients complaining of voiding disturbance who showed gray zone total prostate-specific antigen (t-PSA) level (upper limit of normal approximately 10 ng/ml) but did not reveal apparent cancerous findings in the prostate were examined for free PSA (f-PSA) and prostate volume. According to histological diagnosis, 9 were cancer cases and the other 28 were non-cancer cases. The free/total (F/T) ratio was 0.10 and 0.16 in the cancer and non-cancer groups, respectively (t-PSA; DPC kit, p = 0.03). The t-PSA (DPC and Dinabott kits), f-PSA and PSA density alone did not distinguish these two groups. For diagnosis of cancer, the ratio seemed to be F/T, the most reliable followed by PSA density and t-PSA. When using a 13% F/T, the sensitivity and specificity for cancer detection were 88.9 and 70.8%, respectively. t-PSA measured with the Dinabott kit, showed a similar tendency except that the F/T ratio showed a slight variation. Prostate volume and patient age influenced the F/T slightly, but these factors may not impair the usefulness of F/T.

Aged↗

Concerning the relationship between benefit and radiation risk, and cancers detected and induced, in a breast screening programme.

In a breast screening programme based upon X-ray mammography it is necessary to demonstrate that benefit, from reduced mortality arising from earlier diagnosis, exceeds any potential risk from future induction of breast cancers by ionizing radiation. A rigorous treatment of this problem would be both complex and subject to large statistical uncertainty, even if all necessary data were available. A more simplified approach is to show that the number of cancers detected exceeds the number potentially induced by a sufficient margin. These numbers are relatively well established, but this approach is less satisfactory owing to the question of what would constitute a sufficient margin. This paper attempts to explore a possible relationship between the detection/induction ratio and the benefit/risk ratio, using treatment outcome data from three independent sources and mortality reduction data. Agreement between these four sources is considered to be fair, given the nature of the data. The future screening of older women (over 65 years) is also found to have a significant effect on the final outcome. When current trends in such screening are allowed for, the benefit/risk ratio is found to be only marginally less than the detection/induction ratio.

Age Factors↗

A 3D electrical impedance tomography (EIT) system for breast cancer detection.

A medical device which allows imaging of the distribution of conductivity in 3D in regions below the skin surface has been developed and tested. Its purpose is to enable early detection and preliminary diagnosis of breast tumours. Design of the measuring system and software are described. Results of clinical evaluation of the system are presented. EIT images of healthy and cancerous breasts are presented and discussed. The system is able to visualize various states of the breast and it may be possible to apply it to breast cancer detection.

Breast↗

The role of nuclear medicine in breast cancer detection: a focus on Technetium-99 Sestamibi scintimammography.

Screening mammography in women aged over 50 years reduces breast cancer death by 30%. However, because mammography cannot accurately differentiate benign from malignant lesions, many mammography-directed breast biopsies are benign. In the past decade, methods of "functional breast imaging," including magnetic resonance imaging, scintimammography using single photon emission tomography, and positron emission tomography, have improved the sensitivity and specificity rates of conventional mammography for the detection of breast cancer. The higher specificity of scintimammography is feeding current enthusiasm for the study of its role in early breast cancer detection, as a complement to mammography in the evaluation of indeterminate lesions, and for use in noninvasive axillary staging. This article reviews the applications of radionuclide technology in breast cancer diagnosis and surveillance.

Breast Neoplasms↗

Recurrent cervical cancer: detection and prognosis.

BACKGROUND: Only a small proportion of cervical cancer recurrences is detected during routine follow-up. We investigated which percentage of recurrences is detected during follow-up, which diagnostic tools are helpful to detect recurrent disease and which factors are of prognostic significance once recurrent disease has been established in patients treated for cervical cancer stage IB-IVA. METHODS: Characteristics of the primary tumor, characteristics of recurrent disease and follow-up were collected retrospectively from clinical records of 277 patients who achieved a complete remission of at least 3 months after primary treatment for cervical cancer in 1992, 1993 and 1994 in three university hospitals in the Netherlands. RESULTS: Of 277 patients, 47 (17%) developed recurrent disease; this was most often detected after self-referral (45%), and in 32% during routine follow-up. Survival did not differ significantly between these two groups. The presence of symptoms (87%) was the most important first abnormal test result leading to diagnosis of recurrence. In univariate analysis, disease-free interval (DFI) and treatment modality were significant prognostic factors for crude survival of recurrence. However, treatment modality varied considerably and the subgroups were small. Therefore, multivariate analysis was not feasible and clinically valid conclusions could not be drawn. CONCLUSIONS: In only 32% of all cases, recurrence was detected during a scheduled follow-up visit. In the majority of patients, recurrent cervical cancer was detected by symptoms (87%). In recurrent disease, DFI was a prognostic factor for survival.

Disease-Free Survival↗

Recurrent cervical cancer: detection and prognosis.

BACKGROUND: Only a small proportion of cervical cancer recurrences is detected during routine follow-up. We investigated which percentage of recurrences is detected during follow-up, which diagnostic tools are helpful to detect recurrent disease and which factors are of prognostic significance once recurrent disease has been established in patients treated for cervical cancer stage IB-IVA. METHODS: Characteristics of the primary tumor, characteristics of recurrent disease and follow-up were collected retrospectively from clinical records of 277 patients who achieved a complete remission of at least 3 months after primary treatment for cervical cancer in 1992, 1993 and 1994 in three university hospitals in the Netherlands. RESULTS: Of 277 patients, 47 (17%) developed recurrent disease; this was most often detected after self-referral (45%), and in 32% during routine follow-up. Survival did not differ significantly between these two groups. The presence of symptoms (87%) was the most important first abnormal test result leading to diagnosis of recurrence. In univariate analysis, disease-free interval (DFI) and treatment modality were significant prognostic factors for crude survival of recurrence. However, treatment modality varied considerably and the subgroups were small. Therefore, multivariate analysis was not feasible and clinically valid conclusions could not be drawn. CONCLUSIONS: In only 32% of all cases, recurrence was detected during a scheduled follow-up visit. In the majority of patients, recurrent cervical cancer was detected by symptoms (87%). In recurrent disease, DFI was a prognostic factor for survival.

Disease-Free Survival↗

Breast cancer detected by mass screening using physical examination alone.

In Tokushima prefecture, mass screening for breast cancer has been conducted using physical examination alone since 1970. Breast cancer was detected in 116 of 111,571 screened women up until 1984. The detection rate was 0.08 per cent in total examinees, 0.13 per cent in initial examinees, and 0.04 per cent in subsequent examinees. The patients with breast cancer were divided into three groups, i.e., 62 cases detected at initial screening, 28 cases detected at subsequent screenings, and 26 interval cancer cases. 510 patients with breast cancer in the outpatient clinic were serving as controls. The stage classification and nodal involvement were significantly different between the mass screening group and the control group, but not significantly different among the three groups. The interval cases were detected at an early stage. The survival rates were not significantly different between the three groups and the control group. Efforts should be doubled to educate women about the proper method of breast self-examination in order to promote the early detection of breast cancer.

Adult↗

Expression of early lung cancer detection marker: hnRNP-A2/B1 and its relation to microsatellite alteration in non-small cell lung cancer.

We have reported that a mouse monoclonal antibody, 703D4, which recognizes heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNP-A2/B1) can frequently detect lung cancer in exfoliated sputum epithelial cells 1-2 years earlier than routine chest X-ray or sputum cytomorphology. We along with others have shown that microsatellite alteration (MA) at selected loci can be recognized in sputum cells prior to clinical lung cancer. The present study was undertaken to determine how frequently the expression of hnRNP-A2/B1 message is associated with neoplastic clonal expansion as shown by MA in 41 cases of non-small cell lung cancer (NSCLC). We used Northern blotting to evaluate hnRNP-A2/B1 mRNA expression in lung tumor and remote noninvolved lung. We evaluated microsatellite instability (i.e. shifts; MI) or loss of heterozygosity (LOH) with a panel of 13 microsatellite markers at loci identified previously as susceptible in NSCLC. Of the 41 tumors, 25 (61%) over-expressed hnRNP-A2/B1 and 33 (80%) demonstrated MA in at least one of 13 loci (58% in at least two loci). The association between MA (one locus) and the overexpression of hnRNP-A2/B1 is statistically significant (P=0.0082), and those lung tumors with MA at two or more loci were significantly more likely to over-express hnRNP-A2/B1 mRNA (P=0.004). MA of loci on 3p were the only MA statistically associated with hnRNP-A2/B1 message overexpression (P=0.001). We conclude that lung tumor cells undergoing clonal expansion frequently upregulate hnRNP-A2/B1.

Adult↗

DNA flow cytometric analysis indicates that many breast cancers detected in the first round of mammographic screening have a low malignant potential.

An organized mammographic screening program covered 8,690 women from selected birth cohorts (aged 50-59) in the Tampere University Central Hospital district. Forty-four breast cancer cases were detected in the first round of mammographic screening, which is 3.7 times the expected annual number of new cases in this population. To evaluate the proliferative kinetics and biological properties of these cancers, DNA flow cytometric analysis was carried out in 37 of the screen detected cancers (SDCs) using 60 clinically detected stage I-II cancers and 30 screen-detected benign lesions as reference. DNA aneuploidy was observed in 17/37 (46%) of the SDCs as compared to 41/60 (68%) in the clinical controls (p less than 0.05), while all the benign lesions were DNA-diploid. The median S-phase fraction (SPF) in the SDCs was significantly (p less than 0.001) lower (3.5%) than in the clinical controls (9.6%). Differences in SPF persisted in subgroups defined by DNA ploidy and histological type. In stage-I SDCs the median SPF value (2.5%) approached that of benign tumors (1.9%). Our epidemiological and biological data indicate that the first round of mammography predominantly detects prevalent preclinical lesions, some of which are of very low malignant potential. At present such patients may often receive too extensive treatment. DNA flow cytometry could help in the identification of cases which could be treated, for example, by breast-conserving methods.

Aneuploidy↗

Prostate cancer detection, characterization, and clinical outcomes in men aged 70 years and older referred for transrectal ultrasound and prostate biopsies.

OBJECTIVES: To evaluate the diagnostic findings and treatment options chosen in men aged 70 years and older referred for prostate biopsy. METHODS: Age, prostate-specific antigen (PSA), biopsy pathology, clinical stage, treatment pursued, and treatment outcome were analyzed in 210 men age 70 years and older referred for transrectal ultrasound and prostate biopsies. All patients were followed for a mean of 46.9 months (range 28 to 63). RESULTS: Cancer was found in 120 (56.8%) of the patients. The cancer detection rate was significantly higher (81.0%) in patients aged 80 years and older than those younger than 80 years. Cancer patients aged 80 years and older had a higher rate of poorly differentiated cancer (64.7%) compared with the 70 to 74-year-olds (33.3%) and 75 to 79-year-olds (32.1%). The patients aged 80 years and older also had a larger proportion of high-stage cancer. The patients younger than 80 years had a significantly higher incidence of stable/falling PSA with treatment compared with the older patients. Of the 210 patients, 41 (19.4%) died within 5 years of the diagnostic procedure; 3 died of prostate cancer. The death rate was not significantly different among the three age groups evaluated. None of the patients aged 80 years and older died of prostate cancer. CONCLUSIONS: Patients aged 80 years and older who are diagnosed with prostate cancer are less likely to respond well to treatment and usually die of unrelated causes. Aggressive diagnosis, staging, and treatment in octogenarians should be guided by the patients' symptoms, overall health, and personal preferences.

Age Distribution↗

Applications of machine learning and high-dimensional visualization in cancer detection, diagnosis, and management.

Recent technical advances in combinatorial chemistry, genomics, and proteomics have made available large databases of biological and chemical information that have the potential to dramatically improve our understanding of cancer biology at the molecular level. Such an understanding of cancer biology could have a substantial impact on how we detect, diagnose, and manage cancer cases in the clinical setting. One of the biggest challenges facing clinical oncologists is how to extract clinically useful knowledge from the overwhelming amount of raw molecular data that are currently available. In this paper, we discuss how the exploratory data analysis techniques of machine learning and high-dimensional visualization can be applied to extract clinically useful knowledge from a heterogeneous assortment of molecular data. After an introductory overview of machine learning and visualization techniques, we describe two proprietary algorithms (PURS and RadViz) that we have found to be useful in the exploratory analysis of large biological data sets. We next illustrate, by way of three examples, the applicability of these techniques to cancer detection, diagnosis, and management using three very different types of molecular data. We first discuss the use of our exploratory analysis techniques on proteomic mass spectroscopy data for the detection of ovarian cancer. Next, we discuss the diagnostic use of these techniques on gene expression data to differentiate between squamous and adenocarcinoma of the lung. Finally, we illustrate the use of such techniques in selecting from a database of chemical compounds those most effective in managing patients with melanoma versus leukemia.

Artificial Intelligence↗