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[Early detection of hepatobiliary cancer in mass health screening].

Mass health screening (MHS) for detecting early cancer of hepatobiliary diseases is not common. However, as high risk factors for developing hepatocellular carcinoma (HCC) has been established in Japan, MHS for HCC is available, especially in high endemic areas of hepatitis C. Intrahepatic bile duct cancer often occur in patients with Thorotrastosis. Cohort study for detection of early cancer of intrahepatic bile duct has been conducting by the Japanese Government. Early detection of bile duct cancer in health screening is very rare. It will be helpful for perform MHS to clarify the high risk factors for bile duct cancers.

Adult↗

Circulating tumor human papillomavirus DNA whole genome sequencing enables human papillomavirus-associated oropharynx cancer early detection.

BACKGROUND: Early detection of HPV-associated oropharyngeal squamous cell carcinoma, the most common HPV cancer in the United States, could reduce disease-related morbidity and mortality, yet currently, there are no early detection tests. HPV circulating tumor DNA (ctDNA) is a sensitive and specific biomarker for HPV-associated oropharyngeal squamous cell carcinoma at diagnosis. It is unknown if ctDNA HPV is detectable prior to diagnosis, and thus its potential as an early detection test is also unknown. METHODS: Plasma samples from the Mass General Brigham Biobank collected 1.3-10.8 years prior to diagnosis from HPV-associated oropharyngeal squamous cell carcinoma patients (n = 28) and age- and sex-matched controls (n = 28) were blinded and run on a newly developed and validated multifeature HPV whole genome sequencing liquid biopsy assay and a validated HPV antibody assay. RESULTS: HPV ctDNA results were positive in 22 of 28 prediagnostic samples from HPV-associated oropharyngeal squamous cell carcinoma cases (sensitivity 79%) with a maximum lead time of 7.8 years. HPV ctDNA results were negative in all controls (0 of 28, 100% specificity). Diagnostic accuracy was highest within 4 years of cancer diagnosis and was higher than HPV Ab detection within the same timeframe (P = .004). Application of a machine-learning model trained and tested on an independent cohort of 306 cases and controls increased the sensitivity of detection to 27 of 28 cases (overall sensitivity 96%) and the maximum lead time to 10.3 years. CONCLUSIONS: HPV ctDNA can be detected in the blood years prior to diagnosis with HPV-associated oropharyngeal squamous cell carcinoma, with high specificity, in a case-control cohort of 56 participants. HPV ctDNA detection alone, or in combination with previously identified serological biomarkers, may be a feasible approach to early detection of HPV-associated oropharyngeal squamous cell carcinoma.

Humans↗

Application of cancer procoagulant as an early detection tumor marker.

BACKGROUND: In spite of many advances in the analytical reagents (antibodies), analytical systems, and the clinical application of tumor markers, the present markers do not detect early stage cancer. Preliminary data with an antigen specific to tumor tissue, cancer procoagulant (CP), suggest its possible role in the detection of early stage cancer. This study was aimed at determining the clinical use of CP as an early stage tumor marker. METHODS: An improved enzyme-linked immunosorbent assay (ELISA) was developed to measure CP concentration in serum. A panel of 817 blinded serum samples were examined from three groups of people: 573 cancer, 106 benign, and 139 normal. RESULTS: The sensitivity of all samples analyzed from cancer patients was 80%. The CP ELISA was able to detect ovarian, colon, and kidney cancer at a sensitivity greater than 85%; breast, prostate and small cell lung cancer was detected at a sensitivity of 80-85%. Particularly interesting was the observation that early stage cancers, regardless of site, were detected effectively. In some groups, the CP assay correctly identified 100% of the patients with stage I and II cancer. The assay was able to identify correctly noncancer patient sera at a specificity of 83% for those with benign disease and 82% for the normal individuals. CONCLUSIONS: The CP assay has potential as an aid in diagnosing early stage malignancies and thereby may significantly improve the survival rate of cancer patients.

Adenocarcinoma↗

A survey of physicians' breast cancer early detection practices.

Early detection of breast cancer through the use of mammography reduces long-term mortality from this disease, yet relatively little is known about its acceptance by the medical community. As part of a state health department cancer control program planning effort, we contacted 1,004 primary-care physicians in Pennsylvania to ascertain current breast cancer early detection practices. While 92% of the 557 eligible respondents reported conducting breast physical examinations at least annually in asymptomatic women age 50 or older, annual mammograms for this age group were ordered by only 42% of physicians. Obstetrician-gynecologists, as well as female and younger physicians, were more likely to obtain nondiagnostic mammograms regularly. Factors reported by physicians as affecting their practice of obtaining mammograms varied by patient age and, among patients 50 years and older, included the claim that their mammography practices represented optimal care (57% of the physicians), how often the patient visited their office (23%), patient refusal (16%), and cost of the examination (16%). Fear of radiation and expense were cited as the primary reasons for patient refusal. Public and physician education, as well as third-party payment changes, was viewed by the physicians as the most effective means to increase the level of breast cancer early detection in their geographic areas. This survey shows that the use of nondiagnostic mammography is still less than optimal, and identifies impediments to screening that need to be addressed in cancer control planning efforts.

Adult↗

Early detection of visual field progression in glaucoma: a comparison of PROGRESSOR and STATPAC 2.

AIM: To compare the performance of PROGRESSOR (pointwise linear regression) and STATPAC 2 (comparison with baseline values) in detecting early deterioration in the visual fields of glaucoma patients. METHODS: Visual field series from 19 untreated normal tension glaucoma eyes which were deteriorating on clinical grounds were analysed by PROGRESSOR and STATPAC 2. Progression criteria for PROGRESSOR were (1) inner points: slope < -1 dB/year, p < 0.05 and (2) edge points: slope < -2 dB/year, p < 0.05. Criteria for STATPAC 2 were p < 0.05 change probability for any point on three consecutive fields. Detection time was defined as the time interval between the initial field and the first field in which at least one progressing point was identified. Detection times produced by the two techniques were compared. RESULTS: PROGRESSOR and STATPAC 2 agreed on progression in all 19 eyes. Mean detection time for PROGRESSOR was 1.077 (SD 0.985) years and for STATPAC 2 was 2.161 (1.357) years. PROGRESSOR detected progression sooner than STATPAC 2 in 18 eyes (p < 0.01), Wilcoxon matched pairs signed rank test). PROGRESSOR detected progression earlier by a mean of 1.085 (0.936) years. CONCLUSIONS: PROGRESSOR consistently detected progression earlier than STATPAC 2. The PROGRESSOR software is a useful tool for the early detection of visual field deterioration in glaucoma.

Algorithms↗

Survival of patients with breast cancer diagnosed in the United Kingdom trial of early detection of breast cancer. United Kingdom Trial of Early Detection of Breast Cancer Group.

OBJECTIVE: To examine the survival of patients with breast cancer diagnosed in different centres and by different methods in the United Kingdom trial of early detection of breast cancer, in order to investigate the contribution of different factors to the previously observed reductions in breast cancer mortality. SETTING: A non-randomised trial of the early detection of breast cancer, in which women aged 45-64 in two districts were offered annual screening for seven years, women in a further two districts were offered education about breast self examination (BSE), and those in four districts formed a comparison group. METHODS: Patients with breast cancer are classified according to the type of centre, method of detection, and attendance for BSE education. Univariate and multivariate survival analyses are carried out, including tumour size, dissemination status, and use of adjuvant treatment as additional variables. RESULTS: In the univariate analysis, patients with breast cancer who are non-attenders for screening have a significantly worse prognosis than those in the comparison centres. Patients whose cancer is detected by mammography have the best survival rate. The inclusion of size and dissemination status in the multivariate analysis explains only about one third of the improved prognosis in these cases. There is a significant difference between prognosis in the two BSE centres. CONCLUSIONS: The use of prognostic factors as recorded in this trial to predict breast cancer mortality may be inadequate.

Analysis of Variance↗

Early detection of Borrelia burgdorferi sensu lato infection in Balb/c mice by co-feeding Ixodes ricinus ticks.

In Europe, Borrelia burgdorferi is transmitted by Ixodes ricinus to animals and human. When infected and uninfected ticks co-feed on a host, spirochetes are transmitted from ticks to animal and also to uninfected ticks. Here, we used uninfected ticks to co-feed with infected ticks on mice to evaluate this method to detect early infection in mice. A total of 128 mice were challenged by infected nymphs placed in capsules glued on the back of the mice. Three days later uninfected larvae were added in the capsule to co-feed with infected nymphs and were examined for Borrelia infection after natural detachment. Infection in mice was also determined by xenodiagnosis and by spirochete isolation from ear skin biopsy and back skin biopsy taken at the tick attachment site one month after infection. A total of 111 mice were found to be infected by at least one of these four methods. Borrelia infection was observed in 95% of mice by the co-feeding method, in 92% of mice by xenodiagnosis, in 69% and in 68% of mice by cultivation of ear and back skin biopsies, respectively. Our results demonstrate that the co-feeding method is a very sensitive method which can be used to detect very early infection in mice infected by tick bites.

Animals↗

First results on mortality reduction in the UK Trial of Early Detection of Breast Cancer. UK Trial of Early Detection of Breast Cancer Group.

Between 1979 and 1981 the UK Trial of Early Detection of Breast Cancer enrolled women aged 45-64 living in eight locations in the United Kingdom. Annual screening by clinical examination of the breast, with mammography in alternate years, was provided over 7 years for 45,841 women; 63,636 were offered teaching in breast self-examination and were provided with a self-referral clinic; and 127,117, for whom no extra services were provided, form a comparison population. Over the 7 years from the start of the trial a reduction in the risk of dying from breast cancer in women offered screening relative to that in the comparison population was observed. The reduction was 14% (RR 0.86, 95% CI 0.69-1.08) when no allowance was made for underlying differences in breast cancer mortality between the populations, but rose to 20% (RR 0.80, 95% CI 0.64-1.01) when adjusted for differences in pretrial mortality rates. These differences fall short of statistical significance. No reduction in mortality was observed during the first 5 years but thereafter the gap widens. These results, though in themselves inconclusive, are consistent with the hypothesis that screening can achieve a worthwhile mortality reduction. No difference in mortality has so far been observed between women offered teaching in breast self-examination and the comparison population.

Breast Neoplasms↗

Characteristics of prostate cancers detected in a multimodality early detection program. The Investigators of the American Cancer Society-National Prostate Cancer Detection Project.

BACKGROUND: Few data are available to describe the clinical and pathologic characteristics of prostate cancers detected through early detection programs. The American Cancer Society National Prostate Cancer Detection Project (ACS-NPCDP) is a multimodality, multicenter study of the feasibility of early prostate cancer detection using digital rectal examination (DRE), transrectal ultrasound (TRUS), and prostate specific antigen (PSA). One hundred fifty-six prostate cancers are available from this project for analysis. METHODS: The ACS-NPCDP is a prospective, comparative study of a cohort of 2,999 men between 55 and 70 years of age not suspected of having prostate cancer. DRE, TRUS, and PSA are performed for each subject on an annual basis for as long as 5 years. Biopsies are performed on the basis of recommendations from DRE or TRUS results. Although elevated PSA alone was not typically a basis for biopsy, in some instances biopsies were recommended because of the degree of elevation in PSA. Diagnoses are confirmed by participating pathologists and by pathologic analysis. RESULTS: A small proportion of cancers detected were advanced in terms of the clinical stage at time of diagnosis. A total of only six cancers were stage C1 to D1, and five of these were preexisting cancers detected at the first examination. Cancers detected by DRE tended to be more advanced than those found on the basis of only TRUS or PSA. A large proportion of patients received curative therapy, involving radical prostatectomy for 67.9% and radiation therapy for 17.9%. Of 100 men presumed to have organ confined disease and treated by prostatectomy, 64 actually proved to have localized cancer, a rate of upstaging of 36.0%. PSA level and PSA density were associated with the detection of organ confined cancer, but several advanced cancers had PSA levels in the normal range, limiting the usefulness of these measures for staging. CONCLUSIONS: The cancers resulting from this multimodality detection effort represented a spectrum of pathologic findings. These data, however, suggest that early detection interventions in men not suspected to have prostate cancer will yield tumors with a favorable stage distribution that are likely to benefit from treatment. Further follow-up evaluation is needed to determine whether these benefits are reflected in long-term mortality and survival experience.

Aged↗

Early detection of ovarian cancer: background, rationale, and structure of the Yale Early Detection Program.

Ovarian cancer has received national attention as a highly virulent disease. Its lack of early warning symptoms and the failure to develop highly sensitive screening tests have led some physicians to recommend prophylactic oophorectomies to women with relatives who have had ovarian cancer. Others have recommended routine screening of otherwise normal women for CA 125, a circulating tumor marker, and ultrasound examinations. Each of these techniques is associated with substantial false-positive rates that could lead to unnecessary surgery. A review of epidemiologic data suggests that familial ovarian cancer kindreds are rare, but women with first-degree relatives who have had ovarian cancer have a significant risk themselves for developing ovarian cancer. In addition, women with a great number of ovulatory cycles are at an increased risk for the disease. Circulating tumor markers are frequently elevated in women with advanced ovarian cancer, but their value in early detection of ovarian cancer has yet to be established. Advances in endovaginal ultrasound and color Doppler flow technology have significantly improved our ability to assess pelvic organs. This article presents the background, rationale, and structure of the Yale Early Detection Program for ovarian cancer, whose goals are to identify the best techniques for diagnosing ovarian cancer in an early stage, to determine the frequency with which such tests should be employed, to assess false-positive results, and to identify women who might benefit from prophylactic oophorectomies.

Biomarkers, Tumor↗

[Early detection of prostatic carcinoma in urologic practice with digital rectal examination and prostate-specific antigen. Early Detection Project Group].

For the early detection of prostate cancer, a patient should undergo digital rectal examination (DRE) and PSA investigation. Follow-up of increased PSA levels detects nearly 80% of cancers. Positive predictive value of suspicious DRE and PSA is about 50%. Whereas in the first evaluation of this case-finding trial about 70% of the patients had organ-confined cancers, nearly all of the detected cancers in the follow-up investigation were organ confined. The increased number of organ-confined cancers detected in early periodical examinations can lead to a reduction of mortality and morbidity from prostate cancer.

Adult↗

Early detection of cutaneous malignant melanoma by three-dimensional nevoscopy.

Malignant melanoma is the most lethal form of skin cancer, and often develops from a pre-existing mole (nevus) or the pigment cells of the upper layer of the skin. The incidence of, as well as the mortality rate due to malignant melanoma is increasing relentlessly all over the world. The survival rate may be improved and nearly all patients may be saved if their melanomas are detected early and removed surgically. We have developed a new non-invasive method of imaging nevi and other skin lesions for the detection of three-dimensional changes in the shape and size of such lesions which uses the principles of computed tomography (CT). The skin lesion is transilluminated using fibre optics directed into the skin and images of the transilluminated lesion are obtained at different angles by an optical instrument called a 'nevoscope'. The three-dimensional reconstruction of the lesion is then obtained using new limited-view CT algorithms. A quantitative analysis of consecutive three-dimensional reconstructions demonstrates any changes in thickness, size, color, and structure of the lesion which may indicate the development of a malignant melanoma.

Biometry↗

Early detection of P-VEP and PERG changes in ophthalmic Graves' disease.

BACKGROUND: In Graves' disease the optic neuropathy (ON) is due to direct compression of the nerve and/or of its blood supply. The aim of the present study was to detect early changes in the visual functions of patients affected by ophthalmic Graves' disease (OGD) by using electrophysiological tests (P-VEP and PERG). METHODS: We studied 50 OGD patients who were in a range between class 2 and class 5 according to the Donaldson-American Thyroid Association classification, i.e. had no evident ON and normal visual acuity. We recorded transient reversal PERG and P-VEP in response to the stimulation of one eye at three spatial frequencies (2.2, 1.1 and 0.5 c/d). RESULTS: Our results showed a statistically significant reduction in PERG amplitude in class 5, while the P-VEP amplitude was already reduced in class 2. CONCLUSION: The electrofunctional tests were useful to detect small changes in the visual function of patients affected by initial stages of OGD. Therefore, P-VEP and PERG recordings appear to be a useful tool for early diagnosis of the optic nerve involvement in Graves' disease.

Adult↗

[Early detection and diagnosis of breast cancer].

Various kinds of modalities have been used to detect and diagnose breast cancer. In order to detect early breast cancer, mass screening has been widely performed with physical examinations in Japan and mammography in the U. S and European countries. After detecting some abnormalities within the breast under basic screening, further examinations are required for a precise diagnosis. For this purpose, ultrasonography and/or thermography are used as a noninvasive image examination, and aspiration biopsy cytology and/or surgical biopsy are employed for the final diagnosis. Mammography with highly qualified equipment and its adequate performance is thought to be the most useful modality in basic screening for detecting nonpalpable breast cancer. Ultrasonography is valuable for differentiating whether the lesions detected on screening are malignant or benign. Thermography seems better in analysing the malignant potential of the lesions detected by other examinations. Aspiration biopsy cytology (ABC) is employed for final diagnosis. Fine needle ABC has the highest sensitivity (90.8%) compared to other modalities in this department of Fukushima Medical College Hospital. Positive diagnosis on ABC is not needed for surgical biopsy. However, suspected or negative findings on ABC are required for two-step surgical biopsy which should be performed at the outpatient clinic to obtain detailed information about the biological characteristics as well as pathological diagnosis.

Biopsy, Needle↗

Early detection of schizophrenia by diffusion weighted imaging.

A novel magnetic resonance imaging method was used to determine whether it is feasible to detect early signs of cortical atrophy among individuals who are at high risk for developing schizophrenia. Fifteen individuals at high-risk for schizophrenia and 15 of their first degree relatives diagnosed with schizophrenia were compared with controls (n=25) who did not have a family history of psychiatric illness or psychiatric hospitalizations. On the basis of a voxelwise analysis of apparent diffusion coefficient (ADC) maps derived from diffusion weighted magnetic resonance imaging, these individuals showed evidence of deficits in four separate regions of the brain, all on the left side only: parahippocampal gyrus, lingual gyrus, superior frontal gyrus, and middle frontal gyrus. However, conventional volumetric quantification of ventricular space to detect atrophy failed to reveal differences between high-risk subjects and controls. It is concluded that ADC may be a more sensitive measure than ventricular volume assessments for use in future studies of early prediction of schizophrenia.

Adolescent↗

The use of electro-acoustic impedance measurements in detecting early clinical otosclerosis.

The first evidence that sodium fluoride (NaFl) can stop the otosclerotic process was recently presented. This development has placed new emphasis on the early detection of clinical otosclerosis. Electro-acoustic impedance measurements often detect minute changes in absolute impedance and compliance of the ossicular chain. The most valuable diagnostic information, however, is a negative on-off (biphasic) type of acoustic reflex. These results are often evident prior to the detection of positive clinical signs of otosclerosis. The negative on-off acoustic reflex is reviewed in this paper along with case discussions involving medical/surgical management of early otosclerosis.

Acoustic Impedance Tests↗

[Screening for prevention and early detection of cervical cancer in the German Democratic Republic-- an analysis (author's transl)].

The cytological mass screening to prevent invasive carcinomas by detection and therapy of intraepithelial neoplasia and to detect early stages of invasive carcinomas is the most important basis for cervical cancer control. An analysis of epidemiological effects caused by mass screening programs in two districts (Berlin, capital of the GDR; Rostock) demonstrates during the last 7 years a marked increase of detected ca in situ followed by a clear decrease, a decrease of morbidity of cervical cancer (49.4/100,000 :36.1/100,000 women) and an increase of earlier stages, especially stage Ia. The highest decrease of morbidity could be observed in women aged 40--49 years (111.6 : 61.0) followed by those aged 50--59 years (91.1 : 76.1). Preliminary results demonstrate the benefit of screening program and the practicability of organization form used in the capital Berlin. A further analysis demonstrates screening activities in the whole country. a continuous increase of cytological capacities in many districts is the remarkable result of the activities and gives the assurance for further success of the cytological screening program decided for the German Democratic Republic.

Adult↗