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Prospective evaluation of lateral biopsies of the peripheral zone for prostate cancer detection.

PURPOSE: We evaluate the usefulness of adding 4 lateral biopsies of the peripheral zone to the routine sextant biopsy regimen for prostate cancer. MATERIALS AND METHODS: A total of 273 consecutive patients referred for abnormal digital rectal examination and/or prostate specific antigen 4 ng./ml. or greater underwent transrectal ultrasound and systematic biopsy. Lateral biopsies of the peripheral zone taken just medial to the lateral border of the prostate were added to the routine lesion directed and systematic sextant biopsy regimen. Comparisons between positive and negative biopsy groups as well as among various biopsy schemes were performed. RESULTS: Of the patients 44% had cancer on biopsy (121 of 273). While routine sextant biopsies detected 82% of cancers, 77% (17 of 22) of missed cancers were detected on lateral biopsies. Overall, lateral biopsies detected 70% of cancers, and tended to be positive in patients with small prostates and high grade tumors. A significant correlation was found between hypoechoic lesions on transrectal ultrasound and positive lateral biopsies (Fisher's exact test p = 0.0005). Cancer was found in 74 of 147 patients with lesions on transrectal ultrasound (50%). Routine sextant biopsies detected 76% of cancers (56 of 74 patients) while lateral biopsies detected 80% (59). Of these patients 15 (20%) had positive lateral and negative sextant biopsies. Routine sextant biopsies detected 91% of cancers in 121 patients without lesions on ultrasound (43 of 47). CONCLUSIONS: The addition of lateral peripheral zone biopsies increases the sensitivity for cancer detection while nearly eliminating the need for lesion directed biopsies.

Aged↗

Breast cancer detection by Michaelis-Menten constants via linear programming.

The Michaelis-Menten constants (K(m) and V(max)) operated by linear programming, were employed for detection of breast cancer. The rate of enzymatic hydrolysis of fluorescein diacetate (FDA) in living peripheral blood mononuclear cells (PBMC), derived from healthy subjects and breast cancer (BC) patients, was assessed by measuring the fluorescence intensity (FI) in individual cells under incubation with either the mitogen phytohemagglutinin (PHA) or with tumor tissue, as compared to control. The suggested model diagnoses three conditions: (1) the subject is diseased, (2) the diagnosis is uncertain, and (3) the subject is not diseased. Out of 50 subjects tested, 44 were diagnosed correctly, in 5 cases the diagnosis was not certain, and 1 subject was diagnosed incorrectly.

Breast Neoplasms↗

Colon cancer detection: an algorithm using endoscopy and barium enema.

A review of findings on flexible sigmoidoscopy (FS), colonoscopy and selected double-contrast barium enema (DCBE) radiographs from a group of 66 patients with rectal bleeding was performed to test the value of an algorithm in the detection of colonic cancers and polyps. In this algorithm the FS findings would direct patients either to colonoscopy or to a modified DCBE which focused attention on the colon proximal to the sigmoid. Only patients with neoplasms diagnosed by FS, or by MDCBE after negative FS, would proceed to colonoscopy. The study population contained four cancers, 11 polyps > 5 mm and 11 polyps < or = 5 mm; FS+MDCBE missed four polyps, all < 5 mm. For polyps > 5 mm and cancer, FS+MDCBE had a sensitivity of 100%, a specificity of 82%, a negative predictive value of 1.0 and a positive predictive value of 0.62. Using the algorithm, 24 patients (36%) would have required colonoscopy. The results suggest that FS+MDCBE is a potentially valuable method for screening patients for colonic neoplasia.

Algorithms↗

Volume-specific cutoffs are necessary for reproducible application of prostate-specific antigen density of the transition zone in prostate cancer detection.

OBJECTIVES: To determine the effect of prostate volume on the specificity of prostate-specific antigen density (PSAD) and PSAD of the transition zone (PSA-TZ) in the detection of prostate cancer. METHODS: Between February 1994 and April 1998, transrectal ultrasound-guided prostate needle biopsies were performed in 235 men with serum prostate-specific antigen (PSA) levels between 4.0 and 10.0 ng/mL. The PSAD and PSA-TZ specificities were calculated at 95% sensitivity cutoff levels generated from the whole group, as well as from cohorts stratified by transition zone index or prostate volume. RESULTS: Statistical significance was noted between the benign (n = 176) and prostate cancer (n = 59) groups for all tested PSA parameters. At 95% sensitivity, PSA-TZ carried a specificity of 37.5% compared with 29.6% for PSAD. When applying a single 95% sensitivity cutoff derived from the entire group to individual volume-stratified cohorts, the specificity decreased to 0% in glands less than 30 g in size. A 95% sensitivity PSA-TZ cutoff generated individually for volume-stratified cohorts of glands less than 30, 30 to 40, and 40 to 60 g resulted in more consistent specificity of 28.2%, 35.2%, and 45.7% for each cohort, respectively. CONCLUSIONS: Unlike whole group-derived cutoffs, the use of volume-specific PSA-TZ cutoffs allows consistently high specificity in all volume-stratified cohorts. The discrepancies in the PSA-TZ and PSAD specificities in published reports are likely due to the application of published cutoffs to populations of differing prostate volumes. The use of volume-specific cutoffs results in reproducible specificity in populations with differing prostate volume distribution, and thereby definitively resolves the differences in PSA-TZ specificity reported in published reports.

Biomarkers, Tumor↗

Early prostate cancer detected using expression of non-functional cytolytic P2X7 receptors.

AIMS: To detect early prostate cancer reliably by monitoring the expression of non-functional P2X(7) cytolytic purinergic receptors. METHODS AND RESULTS: P2X(7) receptors were absent from normal prostate epithelium obtained from post mortem tissue and tissue from cases of transurethral resection collected from young men (n = 23) who were confirmed to be free of cancer at later procedures 5-10 years after collection of the original samples. However, P2X(7) was present in every case of 116 confirmed prostate cancers regardless of Gleason grade or patient age. P2X(7) was present in apparently normal epithelial cells in acini well outside the tumour margins, but appeared in a distinct stage-specific manner commencing with the nucleus, progressing to the cytoplasm and collecting finally on the apical membrane of the epithelial cells in morphologically distinct cancer. The pattern of P2X(7) receptor localization in the epithelial cells was recorded in earlier biopsies obtained from the same patient cohort. One hundred and fourteen of 116 prostates stained positively for P2X(7) at the earliest biopsy, though generally with a less advanced pattern of distribution. CONCLUSIONS: The appearance of P2X(7) receptors in normal prostate tissue adjacent to prostate tumours makes direct tumour biopsy less critical for positive cancer diagnosis and enables cancer progression to be monitored.

Aged↗

Preoperative fiber-optic lung cancer detection. A case report.

A case of unexpected detection of bronchial neoplasm in routine general anesthesia is described. On the basis of this case, fiber-optic bronchoscopy in all patients undergoing general anesthesia as a means of early detection of lung cancer is discussed.

Anesthesia, Endotracheal↗

Prostate cancer detection with office based saturation biopsy in a repeat biopsy population.

PURPOSE: Patients at increased risk for prostate cancer with previously negative biopsies pose a diagnostic challenge. We have previously demonstrated that extensive saturation biopsy can be performed in an office setting. We now report the diagnostic yield of office saturation biopsy in patients at increased risk for prostate cancer and at least 1 negative prior biopsy. MATERIALS AND METHODS: We performed saturation prostate biopsy with local anesthesia in the office in 116 patients with at least 1 prior negative biopsy and with certain risk factors, namely persistently elevated prostate specific antigen, abnormal digital rectal examination, or prior atypia or PIN on prior biopsy. RESULTS: A total of 34 cancers were detected for an overall diagnostic yield of 29%. A 64% detection rate was noted when a patient had undergone a single prior sextant biopsy. Subgroup analysis revealed a cancer detection rate of 41% when only prior sextant biopsies were performed, and a 24% detection rate when 10 or more cores were taken on prior biopsy. The detection rate was 33% when only 1 prior biopsy was taken and it was 24% when 2 or more prior biopsies were performed. CONCLUSIONS: Saturation biopsy can be performed safely and effectively in the office with a significant diagnostic yield even in patients with previous extended biopsy schemes. We believe that it should be the next diagnostic step after an initial negative biopsy in patients in whom the diagnosis of prostate cancer is strongly suspected.

Aged↗

Correlation coefficient mapping in fluorescence spectroscopy: tissue classification for cancer detection.

Correlation coefficient mapping has been applied to intrinsic fluorescence spectra of colonic tissue for the purpose of cancer diagnosis. Fluorescence emission spectra were collected of 57 colonic tissue sites in a range of 4 physiological conditions: normal (29), hyperplastic (2), adenomatous (5), and cancerous tissues (21). The sample-sample correlation was used to examine the ability of correlation coefficient mapping to determine tissue disease state. The correlation coefficient map indicates two main categories of samples. These categories were found to relate to disease states of the tissue. Sensitivity, selectivity, predictive value positive, and predictive value negative for differentiation between normal tissue and all other categories were all above 92%. This was found to be similar to, or higher than, tissue classification using existing methods of data reduction. Wavelength-wavelength correlation among the samples highlights areas of importance for tissue classification. The two-dimensional correlation map reveals absorption by NADH and hemoglobin in the samples as negative correlation, an effect not obvious from the one-dimensional fluorescence spectra alone. The integrity of tissue was examined in a time series of spectra of a single tissue sample taken after tissue resection. The wavelength-wavelength correlation coefficient map shows the areas of significance for each fluorophore and their relation to each other. NADH displays negative correlation to collagen and FAD, from the absorption of emission or fluorescence resonance energy transfer. The wavelength-wavelength correlation map for the decay set also clearly shows that there are only three fluorophores of importance in the samples, by the well-defined pattern of the map. The sample-sample correlation coefficient map reveals the changes over time and their impact on tissue classification. Correlation coefficient mapping proves to be an effective method for sample classification and cancer detection.

Adenomatous Polyposis Coli↗

Colorectal cancer detection in the practice setting. Impact of fecal blood testing.

To assess the contribution of fecal blood testing to cancer detection in a clinical practice setting, we studied records from 160 patients with both a new tissue diagnosis of colorectal adenocarcinoma and a preceding stool blood test (HemoQuant, Mayo Medical Laboratories, Rochester, Minn) determination. In this group, 71% had suggestive colorectal symptoms (particularly stool changes, overt bleeding, and abdominal pain) or anemia at presentation, and 29% were asymptomatic. Fecal blood levels remained normal in more than 40% of both symptomatic and asymptomatic patients. In only 26 patients (16% overall) was an abnormal fecal blood level the sole heralding feature, but this subset of patients had a more favorable stage. Fecal blood levels were higher with advanced, larger, and more proximal tumors and with stools collected before purgation. We conclude that, in the practice setting, fecal blood level elevation alone is an uncommon but important manner of colorectal cancer presentation, most cancers present with symptoms, and fecal blood levels are often normal in both symptomatic and asymptomatic patients.

Abdominal Pain↗

Correlation of prostate-specific antigen before prostate cancer detection and clinicopathologic features: evaluation of mass screening populations.

OBJECTIVES: Although prostate-specific antigen (PSA) has become the reference standard for prostate cancer diagnosis, few reports have examined the long-term changes in PSA values before the diagnosis of prostate cancer in a large number of subjects. We investigated serial PSA levels and related values before prostate cancer diagnosis in a mass screening population and analyzed the values in an attempt to discover some values useful in clinical diagnostic science. METHODS: We performed mass screening for prostate cancer in 9671 subjects from 1986 to 1998. The initial screening method was measurement of prostatic acid phosphatase from 1986 to 1991 and measurement of PSA from 1992 to 1998. As a result, 303 cases of prostate cancer were diagnosed. For all the cases diagnosed before 1991, we measured the serum PSA value in preserved frozen serum. RESULTS: The prostate cancer detection rate was 3.1% among all subjects observed during the 13-year period. By measurement of the PSA level using frozen serum during the pre-PSA era, we found that 62% of patients demonstrated a PSA abnormality for more than 1 year (average 2.8) before prostate cancer diagnosis. Prostate cancer that was diagnosed within 1 year after a PSA value became abnormal was not associated with bone metastasis. Concerning the relationship between PSA velocity (PSAV) and clinical stage, the proportion of Stage B cancer was 86% in the subjects whose PSAV level before diagnosis was 0.18 ng/mL/yr or less and it was only 29% in those with PSAV levels of 4.5 ng/mL/yr or more. Only 3 (3.5%) of 86 patients with prostate cancer with PSAV levels of 4.4 ng/mL/yr or less had bone metastasis, and 2 of those 3 patients had poorly differentiated adenocarcinoma. CONCLUSIONS: Although a total of 62% of patients had an abnormal PSA level more than 1 year before prostate cancer diagnosis, no patients with prostate cancer who were diagnosed within 1 year after the PSA level became abnormal had bone metastasis. Among patients who have undergone mass screening twice or more, a clinically useful indicator of the lack of bone metastasis would be a period between the detection of PSA levels of 4.1 ng/mL or more but not more than 10 ng/mL and prostate cancer diagnosis of less than 1 year and a diagnosis of well or moderately differentiated adenocarcinoma or a PSAV of 4.4 ng/mL/yr or less and a cancer diagnosis of well or moderately differentiated adenocarcinoma.

Adult↗

Reasons for failure of physical examination in breast cancer detection (analysis of 232 false-negative cases).

The diagnostic role of physical examination (PE) is evaluated in 1450 cases of breast cancer detected in 34,677 women controlled at the Centro per lo Studio e la Prevenzione Oncologica in the period 1974-1981. In 47 cancer cases, PE findings were normal since the neoplasm was not clinically palpable because of its size and site, and in another 185 cases the clinical diagnosis was benignancy without evidence of suspect signs. Therefore, the overall sensitivity of PE was 84%. PE errors did not involve a therapeutic delay for the patient in 75% of cases in which a biopsy was recommended for clinical benignancy or for suspicion on the basis of other diagnostic methods. The present study confirms that PE has a good diagnostic sensitivity when the examined population is represented by self-referred women, who for the most part are symptomatic, whereas it cannot be considered as the only diagnostic test for early diagnosis in mass screening, since in asymptomatic women a large number of cancers are not clinically palpable. Moreover, PE shows lower sensitivity for small lesions and in younger women. Extensive use of fine needle aspiration cytology and other diagnostic methods in association with PE is therefore recommended to reduce the possibility of errors.

Adult↗

New Swedish breast cancer detection results for women aged 40-49.

The issue of whether to screen women aged 40-49 for breast cancer is debated usually in terms of the potential mortality reduction achievable by the application of screening in this age group. Theories regarding why a significant reduction in mortality has not been observed in trials relate to the biologic behavior of tumors in this age group and the screening process itself. Survival curves with respect to node status, size, and grade of the tumor were compared among age groups in the Swedish two-county trial. In the Kopparberg part of this trial, for the 40-49 age group, predicted survival was calculated from the size, node status, and grade of cancers detected during the trial in comparison with those found in two later series of tumors, one from the 1989-1992, Kopparberg screening program, the other from the British Columbia screening program, the other from the British Columbia screening program that began in 1988. The Kopparberg arm of the Swedish two-county study used single-view mammography with extended processing but without grid; the two more recent programs used two-view mammography with extended processing and the grid. Both the Kopparberg programs used a 2-year interval. The effects of grade, node status, and size on survival in the 40-49 age group were very similar to their effects in older age groups. Predicted survival from the latter Kopparberg series was essentially the same as that for the earlier. The mortality reduction in this age group in the Kopparberg part of the Swedish two-county trial was 26%. The survival results indicate no biologic reason why screening should not be able, theoretically, to reduce mortality. Nonsignificant reductions in mortality have been observed in the Kopparberg part of the two-county trial and in the overview of Swedish trials. The similar predictive results for the two-view and one-view trials suggest that the most likely way to achieve further reductions in mortality is to reduce the interval between screens, possibly to 1 year.

Adult↗

The T-SCAN technology: electrical impedance as a diagnostic tool for breast cancer detection.

In this paper we present the T-SCAN technology and its use as a diagnostic tool for breast cancer detection. We show, using theoretical models with simplified geometries, that displaying planar two-dimensional maps of the currents detected at the breast's surface relate to the electric field distribution within the breast. This distribution is a manifestation of the bulk spatial inhomogeneities in the complex dielectric constant that represent the various tissue types. These differences may be used to discriminate between various pathological states. We furthermore illustrate a useful classifier, based on admittance data measured up to 2 kHz, and we argue that low frequency impedance measurements can be used successfully in breast cancer diagnosis.

Breast Neoplasms↗

Early colon cancers detected by FDG-pet: a report of two cases with immunohistochemical investigation.

Increased glucose uptake is one of the metabolic characteristics of tumor cells. 18F-fluorodeoxyglucose (FDG)-positron emission tomography (FDG-PET), a technique that is used widely to study this altered glucose metabolism in tumors, allows the detection of various types of malignancy. We present herein two cases of early colon cancers detected incidentally by FDG-PET. The technique was used as part of the screening examinations for preoperative staging, and for postoperative follow-up. In both cases, the lesions were removed by colonoscopic polypectomy, with no complications. Moreover, we confirmed the existence of altered glucose metabolism in the resected specimen by immunohistochemical staining using an antibody raised against Glut1. Immunohistochemically, Glut1 was expressed in vitro in both of the lesions, supporting the positive FDG-PET result obtained in vivo. To our knowledge, this is the first report to describe in vitro Glut1 expression and in vivo tumor detection using FDG-PET in colorectal carcinoma.

Adenocarcinoma↗

Enhancing the sensitivity of non-invasive cervical cancer detection using CpG methylation haplotype profiling.

DNA methylation is a critical epigenetic modification that regulates gene expression and plays a significant role in cancer development. This methylation signature can be detected in cancer-derived DNA from non-invasive samples, such as plasma, urine or Pap smears. However, in early-stage cancers-when detection is most critical-the concentration of cancer DNA is often low, limiting the sensitivity of current detection methods. Traditional DNA methylation detection techniques, which rely on methylation ratio-based measurements, may obscure subtle variations in methylation patterns, further reducing detection sensitivity. In this study, we analyzed cervical scraping specimens and examined whether detecting cancer-specific methylation patterns in cervical cancer could be enhanced using a Highly Methylated Haplotype (HMH) approach. This novel approach captures highly methylated haplotypes at single-molecule resolution using next-generation sequencing, providing greater detail than conventional methods. HMHs in specific DNA regions are a hallmark of cancer and stand out in contrast to sporadic methylation commonly observed in non-cancerous tissues. We applied HMH profiling to a gene panel of four biomarkers (CA10, DPP10, FMN2, and HAS1) previously validated in cervical cancer studies. At pre-specified cutoffs (99th percentile of normals), haplotype-based scoring achieved 89.9% sensitivity for invasive cancer at high specificity (~&#x2009;94-98%), outperforming median (78.0%) and single-CpG (71.6%) methods. For clinically relevant endpoints, the combined panel detected 51-52% of CIN2&#x2009;+&#x2009;and 66-67% of CIN3&#x2009;+&#x2009;cases, again exceeding the performance of median- and single-CpG-based scoring methods.These findings demonstrate the potential of HMH to substantially enhance sensitivity in cervical cancer detection, offering a promising approach for non-invasive diagnostics.

Humans↗

Meta-analysis of the risk of gastric stump cancer: detection of high risk patient subsets for stomach cancer after remote partial gastrectomy for benign conditions.

Controversy about gastric cancer risk after partial gastrectomy exists, especially in the United States. Therefore, we performed a meta-analysis to determine overall relative risk and weighted mean relative risk for subsets of postgastrectomy patients, define possible high risk patients suitable for surveillance, and assess for publication bias which would overestimate risk. If 2 studies were excluded because of heterogeneity, overall relative risk (RR) for gastric stump cancer in 22 studies analyzed was 1.66 [95% confidence limits (CL), 1.54-1.79]. With these 2 studies included, the RR summarized with a random effects model to account for study heterogeneity was 1.46 (95% CL, 1.18-1.82). No obvious evidence of publication bias was detected. Patients 15 years or more postoperative had a weighted mean RR of 1.48 (95% CL, 1.31-1.67) and patients 5-14 years postoperative had a RR of 0.91 (95% CL, 0.71-1.17) (P = 0.026). Patients operated upon for gastric ulcer had a weighted mean RR of 2.12 (95% CL, 1.73-2.59) and patients with duodenal ulcers had a RR of 0.84 (95% CL, 0.66-1.05) (P = 0.001). The weighted mean RR for females was 1.79 (95% CL, 1.39-2.29) and for males 1.43 (95% CL, 1.27-1.62) (P = 0.074). For Billroth II gastrectomy the weighted mean RR was 1.60 (95% CL, 1.15-2.18) and for Billroth I gastrectomy 1.20 (95% CL, 1.01-1.42) (P = 0.220). Although differences in risk between subsets of postagastrectomy patients seen to exist, recommendations concerning endoscopic surveillance await further studies of cost-benefit analysis.

Female↗

Prospective evaluation of prostate cancer detection by prostate-specific antigen-related parameters.

BACKGROUND: The diagnostic value of prostate-specific antigen (PSA) for differentiating prostate cancer from benign prostatic conditions is limited by its lack of specificity. Several PSA-related parameters have been suggested as enhancing the discriminatory power of total PSA values, but their clinical utility should be considered preliminary until established in a prospectively evaluated cohort. METHODS: In a prospective cohort study, results of ultrasound-guided biopsy and/or transurethral resection of the prostate gland were assessed in 706 consecutive Japanese men. The clinical usefulness of total PSA, free PSA, percentage of free PSA, PSA density (PSAD), PSA density for transition zone (PSADT) and gland volume for predicting prostate cancer was investigated using receiver operating characteristic (ROC) curve analysis in 16 different patient subgroups. RESULTS: Overall, 150 of the 706 patients (21.2%) had prostate carcinoma. The ROC curve analysis showed that PSAD and PSADT were more powerful predictors of prostate cancer than total PSA in most of the 16 patient subgroups tested. The improvement in performance was modest, however. No substantial difference was noted between PSAD and PSADT. Total gland volume did not significantly affect the performance of these parameters. The use of a PSAD threshold value of 0.11-10.15 ng/mL per cm3 (or a PSADT value of 0.23-0.27 ng/mL per cm3) would have avoided 24-48% (or, for PSADT, 34-40%) of unnecessary biopsies at the cost of missing 5-10% of detectable cancers in a patient subgroup with intermediate total PSA levels. The performance of free PSA and percentage of free PSA was worse than that of any other test in this study. This may be due to inappropriate handling of sera prior to measurement. CONCLUSIONS: The discriminatory potential of total PSA for predicting prostate cancer was modestly improved by the use of PSAD and PSADT. No substantial advantage of PSADT over PSAD could be demonstrated. Stringent and standardized storage conditions should always be maintained when applying free PSA-related parameters.

Aged↗