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Factors associated with accurate cancer detection during a clinical breast examination.

PURPOSE: Although most US women who undergo mammography screening also receive a Clinical Breast Examination (CBE), factors that predict cancer detection during a CBE have not been well studied to date.METHODS: We analyzed 752,081 National Breast and Cervical Cancer Early Detection Program (NBCCEDP) screening records for CBEs performed from July 1, 1995 thru June 30, 1998 on low income women across the US. CBE results are reported as "normal" or "abnormal, suspicious for cancer." Other variables include CBE date, age, race, ethnicity, presence of breast symptoms at screening, and whether the woman had received a prior NBCCEDP-funded CBE. Most (74%) records include mammography dates and results. Tumor stage and size are reported for invasive cancers whether detected by CBE or mammography.RESULTS: Breast cancer was reported on 3,780 records. On 2,224 records, the CBE was suspicious for cancer. On 1,556 records, the CBE was normal. Most (93%) cancer records with a normal CBE had abnormal mammography results. Bivariate comparisons between normal and abnormal CBE records with a cancer diagnosis found significant differences (p <.001) in age, race/ethnicity, presence of breast symptoms, history of a prior NBCCEDP CBE, and tumor stage and size. In a logistic model controlling for these variables, women with breast symptoms were more likely to have their cancer detected during CBE (OR = 7.0, 95% CI = 5.9-8.5), while women with a prior NBCCEDP CBE were less likely to have their cancer detected (OR = 0.7, 95% CI = 0.6-0.8). Compared to women aged 50-59 years, women <40 were more likely to have their cancer detected by CBE (OR = 3.2, 95% CI = 1.9-5.4) but women >/=70 were less likely (OR = 0.7, 95% CI = 0.5-0.9). Larger cancers and those at more advanced stages were much more likely to be detected during CBE.CONCLUSIONS: Among low-income women whose cancers were detected through the NBCCEDP, older women and those who had been screened previously in the program were less likely to have their cancer detected during a CBE, even after controlling for tumor size and stage.

Journal Article↗

Impact of added biopsy areas on prostate cancer detection: preliminary analysis.

OBJECTIVE: To evaluate variations in prostate cancer detection relevant to the number and areas of biopsy cores. METHODS: Ninety patients with elevated prostate-specific antigen levels, abnormal physical examination findings, or both had ultrasound examinations plus biopsies. Forty-nine patients had 11 biopsies, and 41 patients had 6 biopsies. The numbers of cancers detected were compared on a patient-by-patient basis and by all biopsy sites grouped together. An analysis of the relationship between a positive gray scale sonographic finding and the presence of adenocarcinoma was done. RESULTS: On a patient-by-patient basis, 43% of patients who had 11 biopsies had adenocarcinoma. In patients who had 6 biopsies, 32% had adenocarcinoma. Thirty-eight percent of the additional cancers found in the 11-biopsy group were in 5 additional areas not sampled in the 6-biopsy group. Of the total of 539 biopsy specimens obtained in the 11-biopsy group, 56 (10%) had adenocarcinoma; 43% of these 56 were positive in the 5 additional areas not sampled in the 6-biopsy group. No statistical differences (P > .05) were found for mean age, mean prostate-specific antigen level, and mean volume in the groups with 11 and 6 biopsies. This indicated that the observed difference was not related to any of these factors. Similar pathologic data were found for patients with prostatic intraepithelial neoplasia. CONCLUSIONS: Our data indicate the added value of additional biopsy sites over the usual 6 biopsies to increase the yield of adenocarcinoma and prostatic intraepithelial neoplasia detected. The added biopsy sites of the central and midperipheral glands were areas where additional specimens positive for adenocarcinoma and prostatic intraepithelial neoplasia were obtained.

Adenocarcinoma↗

Comparative efficiency of prostate-specific antigen screening strategies for prostate cancer detection.

CONTEXT: Despite widespread use of serum prostate-specific antigen (PSA) testing to detect prostate cancer, the relative effectiveness of different PSA screening strategies is unknown. OBJECTIVE: To compare prostate cancer mortality, PSA testing rates, and biopsy rates using various PSA screening strategies, including the standard strategy of annually testing men aged 50 through 75 years. DESIGN AND SETTING: A Monte-Carlo simulation based on a Markov model was used to simulate the natural history of prostate cancer using different starting ages, testing intervals, and PSA thresholds for prostate biopsy. Age-specific PSA levels and prostate biopsy detection probabilities were determined from population data and surgical series. MAIN OUTCOME MEASURES: Numbers of prevented prostate cancer deaths, PSA tests, and prostate biopsies per 1000 men aged 40 through 80 years, compared among 7 different strategies vs no screening. RESULTS: Compared with annual PSA testing beginning at age 50 years, the strategy of PSA testing at ages 40 and 45 years followed by biennial testing beginning at age 50 years was estimated to simultaneously reduce prostate cancer mortality and number of PSA tests and biopsies performed per 1000 men. Specifically, compared with no screening, the standard strategy prevents 3.2 deaths, with an additional 10,500 PSA tests and 600 prostate biopsies, while the earlier but less frequent strategy prevents 3.3 deaths, with an additional 7500 PSA tests and 450 prostate biopsies. Strategies that lowered the PSA threshold for prostate biopsy to below 4.0 ng/mL or strategies that used age-specific PSA levels were not more efficient than use of a PSA threshold of 4.0 ng/mL. These 2 findings remained true under all sensitivity analyses performed to test assumptions of the model. CONCLUSION: Recognizing that the efficacy of PSA screening is unproved, the standard strategy of annual PSA screening beginning at age 50 years appears to be less effective and more resource intensive compared with a strategy that begins earlier but screens biennially instead of annually. JAMA. 2000;284:1399-1405.

Adult↗

Novel serum small extracellular vesicle miRNAs with multi-target RCA-CRISPR sensor for liver cancer detection.

BACKGROUND: Detecting liver cancer (LC) remains a significant challenge in clinical practice. Small extracellular vesicle (sEV) miRNAs show promise as non-invasive biomarkers for LC detection, yet their diagnostic potential remains largely unexplored. This study aimed to identify specific sEV miRNA signatures for LC detection and develop a novel synchronized multi-miRNA detection platform to enhance diagnostic efficiency and sensitivity. METHODS: High-throughput sequencing was conducted across four distinct cohorts: normal controls (NC), hepatitis B virus (HBV) patients, liver cirrhosis patients, and LC patients. This sequencing process identified miRNAs with differential expression, followed by RT-qPCR validation in serum sEV miRNAs from LC patients and NC. An innovative detection method, RCA-CRISPR, was introduced, combining rolling circle amplification (RCA) with CRISPR/Cas12a (RCA-CRISPR) for quick and sensitive miRNAs detection. RESULTS: Sequencing results showed a consistent elevation of hsa-miR-203b-5p, hsa-miR-4661-5p, and hsa-miR-219a-2-3p across all cohorts. RT-qPCR validations confirmed significant upregulation of these miRNAs in serum sEVs from LC patients, and the combined three-miRNA panel exhibited high diagnostic accuracy (p&#x2009;=&#x2009;0.0003; AUC&#x2009;=&#x2009;0.81). The RCA-CRISPR method demonstrated a detection limit of 3.12 pM for simultaneous multi-target miRNA detection, highlighting its exceptional sensitivity. CONCLUSIONS: Our study identifies hsa-miR-203b-5p, hsa-miR-4661-5p, and hsa-miR-219a-2-3p as promising sEV miRNA biomarkers for LC detection. The developed RCA-CRISPR sensor provides a robust tool for multi-miRNA analysis, potentially advancing non-invasive LC diagnostics. Future validation in larger, prospectively collected cohorts is essential to establish the clinical utility and performance of this biomarker panel and RCA-CRISPR sensor.

MicroRNAs↗

Survival advantage differences by age. Evaluation of the extended follow-up of the Breast Cancer Detection Demonstration Project.

BACKGROUND: This study considers breast cancer survival patterns by age group among women diagnosed in the Breast Cancer Detection Demonstration Project (BCDDP) to provide insight into the nature of breast cancer and suggest a possible explanation as to why the results of the randomized clinical trials differ for women younger than 50 and those 50 or older. Based on the findings of several randomized clinical trials, there is a general consensus that breast cancer screening provides a significant benefit for women aged 50-69. From these trials, there is little evidence of a short term benefit and uncertainty regarding any long term benefit of mammographic screening for women aged 40-49. METHODS: The BCDDP was not a randomized trial, but a nationwide breast cancer screening program conducted between 1973-1980, in which all participants received annual physical and mammographic examinations. Using the BCDDP data, this study calculated 14-year breast cancer survival among 4051 women diagnosed with breast cancer between 1973 and 1980 and followed through 1988 and 1989. RESULTS: In all, 598 women died of breast cancer, resulting in an overall 14-year breast cancer survival of 83.4% (standard error = 0.007). Breast cancer survival varied by tumor type, lymph node status, tumor size, and stage at diagnosis. For most of the cases, however, both the distribution and breast cancer survival rates were similar for women aged 40-49, 50-59, and 60-69 across all prognostic indicators. Only breast cancer survival among women with invasive breast cancer who had a primary tumor 5 cm or larger or with positive lymph nodes differed by age, with women aged 60-69 at diagnosis having poorer survival. Analyses by modality of detection conducted in a subset of 2739 cases indicated that the 34.6% of the cases detected by mammography alone had the highest overall breast cancer survival rates (90.9%), while the 32.2% of the cases detectable by both physical examination and mammography had the lowest breast cancer survival (79.0%). Overall, women diagnosed with breast cancer in the BCDDP had a survival advantage if diagnosed with either a smaller tumor or no positive lymph nodes, or if their breast cancer was detected by mammography alone. For women with large tumors (> or = 5 cm), the survival was 80.8% for ages 40-49, 72.1% for ages 50-59, and 61.7% for ages 60-69. DISCUSSION: Due to the higher breast cancer survival rates among women aged 40-49 with poorer prognostic characteristics, the breast cancer survival advantage for having a smaller tumor, no positive lymph nodes, or breast cancer detected by mammography alone was lower for women aged 40-49 than women aged 50 or older at diagnosis. These differences in survival advantage may help to account for the differences in mortality by age in the randomized clinical trials.

Adult↗

Prostate cancer detection among men with prostate specific antigen levels of 2.5 to 4.0 ng/ml in a Japanese urological referral population.

PURPOSE: Prostate cancer detection at levels of 2.5 to 4.0 ng/ml in a Japanese urological referral population has not been elucidated. The purpose of this study is to investigate the cancer detection rate and clinical relevance of prostate cancer in this PSA range. MATERIALS AND METHODS: All urological patients 70 years or younger tested for prostate cancer were studied. There were 550, 97, 112 and 52 patients with a PSA of less than 2.5, 2.5 to 4.0, 4.1 to 10.0 and more than 10.0 ng/ml, respectively. Transrectal 10-core prostate biopsy was performed in 80 (82%) of the 97 patients with a PSA of 2.5 to 4.0 ng/ml and 102 (91%) of the 112 patients with a PSA of 4.1 to 10.0 ng/ml. RESULTS: Cancer detection rates in patients who underwent biopsy were 26.3% and 34.3% at PSA levels 2.5 to 4.0 and 4.1 to 10.0 ng/ml, respectively. High grade cancers with Gleason score 7 or more were found in 19.0% and 22.9% of patients with cancer with PSA 2.5 to 4.0 and 4.1 to 10.0 ng/ml, respectively. No significant difference was found between the 2 groups in pathological findings on biopsy, including percent positive cores (16.7% vs 20.0%, p = 0.10), maximum cancer length (25.0% vs 30.0%, p = 0.28) and maximum percent cancer length (2.0 vs 3.0 mm, p = 0.17). CONCLUSIONS: Japanese urological referral patients develop prostate cancer quite commonly even if their serum PSA levels are 2.5 to 4.0 ng/ml. Since these cancer cases include high grade, clinically significant cancer, prostate biopsy might be considered at least for selected cases in this PSA range.

Aged↗

Mammography and breast cancer detection by race and Hispanic ethnicity: results from a national program (United States).

OBJECTIVE: Some of the racial and ethnic variation in breast cancer incidence rates may reflect differential use of mammography. We report breast cancer rates using mammography and diagnostic data from five race/ethnicity groups. METHODS: Mammography data were analyzed for 573,751 women who received breast cancer screening between July 1991 and March 1998 from the National Breast and Cervical Cancer Early Detection Program (NBCCEDP). Abnormal mammography rates, breast cancer detection rates, and cancer stage distribution data are presented by race/ethnicity and screening round (first or subsequent). RESULTS: For the first screening round, percentages of abnormal mammographies ranged from 7.3% among black women to 9.3% among Asian/Pacific Islander women. Cancer detection rates ranged from 4.9 cancers per 1000 mammograms for Hispanic and American Indian/Alaska Native (AI/AN) women to 7.7 per 1000 for white women. Subsequent round rates were lower but varied similarly. AI/AN women had the highest percentage (68%) of first-round cancers detected in the early stage (range for the other groups: 52-63%). CONCLUSIONS: Breast cancer detection rates for racial and ethnic groups in this program varied less than published population-based incidence rates. Differential use of mammography among these groups may account for some of the variation reported for breast cancer incidence.

Adult↗

Clinical performance of the AMDL DR-70 immunoassay kit for cancer detection.

A clinical study using DR-70 immunoassay for the detection of 13 different cancers have been conducted with 277 healthy subjects and 136 cancer patients. The test results showed that the DR-70 immunoassay kit was capable of detecting cancers with high degree of specificity and sensitivity. At 95% specificity level, the sensitivity of the assay was 87.8%, 92.6%, 65.2% and 66.7%, respectively for lung, stomach, breast and rectum cancers. Furthermore the test kits were shown to be stable and performed reproducibly.

Adolescent↗

Encouraging screening mammograms. Results of the 1988 Connecticut Breast Cancer Detection Awareness Campaign.

Connecticut's first Breast Cancer Detection Awareness Campaign during April 1988 offered low-cost screening mammograms ($50) to women over age 34 who had not been previously examined. Following a brief mass media campaign, some 2,500 inquiries about the program were received over a seven-day period, resulting in 1,243 examinations of the detection of eight breast cancers. Program participants cited an enhanced awareness that a baseline examination was due, and knowledge about the availability of low-cost services as reasons for obtaining a screening mammogram. Their reasons for not having been previously screened included not having been advised by physicians to have such an examination (28%); high cost (37%); and failure to recognize the importance of periodic screening (21%). By contrast, relatively few women expressed concern about the test procedure (12%), or fear of finding cancer (9%) as reasons for not being screened previously. These findings underscore the benefit of cancer control efforts to reduce access and information barriers to regular use of mammography by women.

Adult↗

Incident screening cancers detected with a second mammographic view: pathological and radiological features.

Previous studies and epidemiological data from the UK National Health Service Breast Screening Programme (NHSBSP) have indicated significantly increased sensitivity for cancer detection with two-view rather than one-view mammographic screening. The radiological and pathological features of these extra cancers have not been previously reported in detail. We have studied all screen-detected cancers found as incident cases in the South West London Breast Screening Service between 1994-1997 on the second round of screening. To assess the effect of two-view versus one-view mammography on cancer detection, these cases were mixed with controls in a 1:2 ratio in nine test sets and each set read independently by three film readers. They initially read the oblique view, then the craniocaudal views, and recorded abnormalities on the films and likelihood of recall. Radiological and histological data were recorded for each case. Using two views, 8.9% (P < 0.05) more invasive cancers were detected. The sensitivity increase was highest for invasive cancers less than 10 mm (11%) and cancers of low grade (11.9%). These sensitivity increases may underestimate the increase in 'real life' because of over-recalling of normal mammograms, particularly with one view, under study conditions. The most significant radiological feature of invasive cancers was an irregular mass, which, seen on one view had a positive predictive value of 82.2% and 89.9% with two views. The craniocaudal view was helpful, firstly, because some cancers were not visible on the oblique view only. Secondly, benign appearing round masses and asymmetric densities seen with the oblique view only were resolved as more suspicious irregular masses with both views, leading to recall. In conclusion, there are cancers that cannot be adequately visualized on the oblique view alone. These are most commonly the small invasive cancers, which are of the greatest prognostic significance in breast cancer screening.

Breast Neoplasms↗

Emerging technologies in breast cancer detection.

While screening mammography is recognized as the most effective method for early detection of breast cancer, this modality has limitations that are the driving force behind efforts to refine existing mammography technologies and develop new ones offering improved detection of breast cancer. Full-field digital mammography (FFDM) systems use digital detectors to convert x-ray photons to digital signals for display on high-resolution monitors. These systems offer capabilities not provided by conventional film-screen mammography. Contrast-enhanced mammography utilizes the basic biological principle that aggressive cancers are associated with increased vascularity. Iodinated contrast agents--the same used in computed tomography (CT) examinations--are administered through an injection in a vein usually in the arm. They distribute throughout the blood system, and x-ray imaging shows increased contrast in areas where they concentrate. Tomosynthesis acquisition involves acquiring multiple images of a stationary compressed breast at different angles during a short scan. The individual images are then reconstructed into a 3D series of thin high-resolution slices. The slices can be displayed individually or in a dynamic ciné mode. The individual slices reduce tissue overlap and structure noise relative to standard 2D projection mammography, with a total dose comparable to that required for standard screening mammography. Initial efforts are underway to develop prototype systems to achieve high-resolution, whole-breast 3D ultrasound images that are co-registered with digital mammograms. This technology has the potential to improve specificity in breast imaging studies, particularly in dense breasts. Computer-aided detection (CAD) programs are intended to help radiologists identify suspicious lesions that may otherwise be overlooked. CAD software works similarly to a spellchecker and has the potential to increase the detection of cancer Magnetic resonanace imaging (MRI) is a generally accepted diagnostic procedure for a number of breast related indications. Its greatest strength is that it is very sensitive to tumors. If a suspected area does not exhibit contrast agent uptake, the probability that it is malignant is very small. Conversely, its specificity is poorer. If the area does show enhancement, it may or may not be a tumor. Further imaging or biopsy may be needed to resolve the question. Ultrasound holds promise as a method for detection of cancers in women with dense breast tissue, which is often problematic with conventional film-screen mammography. Ultrasound has also assumed an important role in breast imaging, as an adjunct to diagnostic mammography for biopsy guidance, palpable mass evaluation, and serial evaluation of benign masses.

Breast Neoplasms↗

Screening for breast cancer detects tumours at an earlier biological stage.

Between August 1988 and July 1990, 17,678 women in the Gateshead, Sunderland, South Tyneside and Durham districts attended the national breast screening programme. A total of 131 cancers were detected. The morphology of cancers detected by screening was compared with that of tumours in 71 patients presenting clinically in the same period. Screen-detected cancers included a higher proportion of tumours of more favourable histological grade and type, were smaller in size and had less axillary lymph node involvement than those detected clinically. Survival was predicted from the Nottingham Prognostic Index. Patients with screen-detected cancer had an expected survival advantage (95 per cent confidence interval) of 26.5 (12.3-40.6) per cent at 5 years, 26.5 (11.8-41.2) per cent at 10 years and 29.1 (14.5-43.7) per cent at 15 years. This survival advantage in screened patients expected at 5, 10 and 15 years is consistent with the 30 per cent reduction in mortality rate demonstrated in the Health Insurance Plan study and the Swedish two counties trial.

Breast Neoplasms↗

Invasive colorectal cancer detected up to 3 years after a colonoscopy negative for cancer.

BACKGROUND AND STUDY AIMS: Colonoscopy has replaced barium enema as the primary method for direct diagnosis of colorectal cancer, but detection may fail, and the reasons for this are not completely understood. PATIENTS AND METHODS: In order to analyze the accuracy of colonoscopy for detecting invasive colorectal cancer, 7365 colonoscopic examinations were matched with the most accurate local government population-based cancer registry in Japan. RESULTS: In 15 colonoscopic examinations, patients were not diagnosed as having invasive colorectal cancer, but disease of this type was detected within 3 years of the examinations (false-negative examinations). During the same period, 233 colonoscopies were identified as true-positive examinations. The false-negative rate for detecting invasive colorectal cancer with colonoscopy was 6% at 3 years. The false-negative rate was significantly higher in individuals between 60 and 69 years of age and in invasive cancers located to the right of the splenic flexure. CONCLUSIONS: Colonoscopists should receive adequate training in achieving easy cecal intubation, detecting small or flat lesions, and carrying out adequate biopsies.

Colonoscopy↗

Use of hormone therapy and risk of breast cancer detected at screening and between mammographic screens.

Postmenopausal hormone therapy (HT) is associated with increased risk of breast cancer, but in women undergoing breast cancer screening it is not clear whether use of HT is associated with increased risk of breast cancer detected at screening or between screens (interval cancer). Further, it is unclear whether the use of the HTs that have been common in Scandinavia is associated with higher risk of breast cancer than the HTs used in other countries. Our study was based on data from 296,651 women aged 50-69 years, who participated in the Norwegian Breast Cancer Screening Program during 1995-2004. After a mean enrollment time of 3.8 years, 1,512 women were diagnosed with invasive screen detected breast cancer, and 814 with invasive interval breast cancer. Cox regression models were used to estimate hazard ratios (HRs) of breast cancer associated with HT use, after adjusting for confounders. Ever users of HT had a 58% increased risk of breast cancer, compared to never users. The HRs associated with HT use were 1.45 (95% confidence interval (CI) = 1.29-1.63) for screen detected and 1.89 (95% CI = 1.61-2.23) for interval cancer. The difference between screen detected and interval cancer was statistically significant (p = 0.011). The HR of breast cancer increased with duration of HT use, but significantly more so for interval than for screen detected cancer (use of HT for 5 or more years compared to never use; HR = 2.91, 95% CI = 2.10-4.04 and HR = 1.94, 95% CI = 1.51-2.50, respectively; p = 0.002). The population attributable fraction of breast cancer due to HT use was 19.8% overall. Ever users of HT tended to develop a cancer of lower grade. No other differences in histological tumor characteristics were observed between ever and never users of HT among screen detected or interval cancers. The estimated risks of either breast cancer overall with HT use are higher in Norway than reported in similar studies from the U.S. HT-use is a stronger risk factor for interval cancer than for screen detected cancer. The increased risk of interval cancer, which may partly be due to decreased sensitivity of mammograms in HT users, remains a challenge in breast cancer screening programs.

Aged↗

Comparisons of interval breast cancers with other breast cancers detected through mass screening and in outpatient clinics in Japan.

In a nation-wide collaborative study on mass screening for breast cancer, we collected 152 cases of interval breast cancer diagnosed at 35 hospitals or clinics distributed throughout Japan. The definition of interval breast cancer used in the present study is "breast cancer cases which were diagnosed as having 'no malignant findings' in a previous screening for breast cancer but subsequently diagnosed as 'breast cancer' at a hospital or medical clinic within two years of the previous screening." The clinical stages and prognoses of these interval cancer were analyzed and compared with those of other breast cancers detected through mass screening and in outpatient clinics. In the clinical staging of interval breast cancer, Tis (non infiltrating cancer) accounted for only 2.1%, compared to 8.0% in cases detected through mass screening. At stage I 43.4% were interval breast cancers compared to 32.9% breast cancers detected through mass screening and 25.4% diagnosed in outpatient clinics. The stage differences between interval breast cancers and breast cancers detected through mass screening were not statistically significant. Five-year survival rates were 85.6% for interval breast cancers, 91.7% for breast cancers detected through mass screening and 84.7% for breast cancers diagnosed in outpatient clinics. Ten-year survival rates were 75.9, 80.5 and 78.1%, respectively, suggesting the interval breast cancer cases to show a similar prognosis to that of breast cancer cases diagnosed in outpatient clinics. The differences in five- and 10-year survival rates among the three groups were not statistically significant. From the present study we were not able to confirm the general belief of interval cancer being more aggressive in nature and showing a poorer prognosis than cancer detected through periodic screening. The reasons for this are discussed.

Adult↗

[Prostate cancer detection by prostate biopsy among Japanese with prostate-specific antigen below 4.0 ng/ml].

The cases of prostate cancer diagnosed at our hospital after the introduction of transrectal ultrasound-guided prostate biopsy were analyzed to ascertain the cancer detection rate among individuals with a prostate-specific antigen (PSA) below 4.0 ng/ml and to assess the pathological characteristics of the prostatectomy specimens. During the period from January 1997 to December 2003, 1,167 individuals received prostate biopsies at our hospital. Before March 2003, the PSA cut-off level for biopsy was set at 4.0 ng/ml, but a biopsy was sometimes performed if a rectal examination revealed abnormalities or the patient desired a biopsy with a PSA below 4.0 ng/ml. After April 2003, all individuals with a PSA over 3.1 ng/ml were biopsied. The results of the prostate biopsy and the pathology data on radical prostatectomy specimens were compared between individuals with a PSA below 4.0 ng/ml and those with a PSA of 4.1-10 ng/ml. The prostate cancer detection rate among individuals with a PSA between 3.1 and 4.0 ng/ml was 19.4% (12/62) before March 2003 and 15.6% (7/45) after April 2003. The number of cancer-positive core was significantly lower among individuals with a PSA below 4.0 ng/ml. On prostatectomy specimens the percentage of surgical margin positive cases was significantly higher among individuals with a PSA below 4.0ng/ml (17 cases) than those with a PSA of 4.1-10 ng/ml (67 cases), although there was no significant difference between these two groups in terms of the pathological stage and Gleason score. Our results indicate that the prostate cancer detection rate is also high among Japanese men with a PSA below 4.0 ng/ml. The biopsy results and pathological features for prostate cancer with a PSA below 4.0 ng/ml did not differ markedly from prostate cancer with a PSA in the gray zone (4.1-10.0 ng/ml).

Aged↗

A simple and practical technic for detecting cancer cells in urine and urinary bladder washings by flow cytometry.

DNA measurement by flow cytometry has been demonstrated to be a potentially useful technic in the diagnosis of bladder cancer by detecting neoplastic cells in bladder washings and urine specimens. The authors' goal was to develop a simple and practical method utilizing the new generation of cytofluorographs designed for use in the clinical laboratory. This method combined direct fixation with cell lysis yielding fixed intact nuclei. Following RNase and pepsin digestion, the nuclei were separated from debris and aggregates on a sucrose barrier, stained with ethidium bromide, and analyzed with an argon laser analytic cytofluorograph. Urines and bladder washings from 14 patients with positive urinary cytology and histologically diagnosed bladder cancers were compared with specimens from patients without urothelial malignancies. DNA histograms clearly delineated aneuploid from diploid populations and often identified S, G2M, and G1 phase nuclei. Aneuploid populations have been detected in all tumor specimens with positive cytologies studied to date.

Aged↗

Expression of early lung cancer detection marker p31 in neoplastic and non-neoplastic respiratory epithelium.

In an immunocytochemical study of sputum, two antibodies, including a mouse monoclonal antibody (703D4) to a 31 kDa protein (p31) antigen, have been previously shown to detect lung cancer earlier than routine cytomorphology or chest X-ray. To understand the basis of p31 expression, the distribution of this antigen in the respiratory epithelium of individuals known to have lung cancer was mapped. These individuals are likely to demonstrate extensive changes throughout the epithelium due to field cancerization. p31 immunoreactivity was examined in primary tumors and surrounding non-neoplastic lungs containing both histologically normal and abnormal areas obtained from 28 Stage I non-small cell lung cancer (NSCLC) patients. Distribution and intensity of p31 expression was scored in three lung compartments (bronchi, bronchioli, alveoli). While p31 was present in histologically unremarkable bronchial and bronchiolar epithelium, no expression was detected in bronchi or bronchioli containing histologic abnormalities. Furthermore, in the peripheral lung p31 staining was frequently observed in alveolar type II cells and was most commonly detected in reactive, hyperplastic type II cells. When p31 immunoreactivity was correlated with clinicopathological features, a statistically significant increase in p31 expression was found both in bronchioli and alveoli of older individuals a well as in bronchioli of patients with most extensive smoking exposure. We conclude that p31 expression occurs in both non-neoplastic and neoplastic epithelium of the human respiratory tract. The increased expression of p31 in the peripheral lung may be potentially informative as to what critical cell populations are involved in the development of invasive cancers. Moreover, this study provides a model approach for analysis of the nature of early epithelial changes leading to the development of lung cancer.

Antibodies, Monoclonal↗