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Has this patient a cancer? The assessment of weight loss, anemia and erythrocyte sedimentation rate as diagnostic tests in cancer. A retrospective study based in a secondary care university hospital in Romania.

INTRODUCTION: "Has this patient a cancer?" is a question we frequently ask ourselves in front of some symptoms, signs or laboratory results like weight loss, anemia and high erythrocyte sedimentation rate (ESR). The aim of this study is to assess their value in the diagnosis of cancer. METHODS: A retrospective study of the records of 5500 patients admitted in the Department of Internal Medicine during the 1998 January-September period has been performed, selecting those patients with weight loss, anemia (Hb < 10.5g/dl) and ESR > = 50 mm/h. RESULTS: The three diagnostic tests (anemia, high ESR and weight loss) had a low sensitivity (37, 52 and 46%, respectively), but a good specificity (92, 89 and 94%, respectively). For a 4% prevalence of cancer, as seen in our group, the resulting negative predictive value for the three tests was estimated respectively at 97, 98 and 98%, the post-test probabilities being estimated at 3, 2.2% in the case of negative tests. For a parallel utilisation of the tests, the sensitivity was 87%, the specificity 79%, the positive predictive value 15% and the negative predictive value 99%, the post-test probability in the case of a negative test being 1% [LR(-) = 0.17]; for serial utilisation, the specificity grew at 99.6% (CI: 99-100%), the positive predictive value (as the post-test probability in the case of a positive test) being 51% (CI: 50-53%) [LR(+) = 24.62]. INTERPRETATION: Any patient admitted in our department of Internal medicine has a 4% probability of having a cancer. Among those with weight loss, anemia and high ESR, one patient out of two has a cancer; among those with weight loss and anemia, 44% have a cancer; and among those with weight loss and high ESR, one out of three has a cancer.

Anemia↗

The role of imaging in prostate cancer.

For patients with prostate cancer, diagnostic imaging can play three roles: screening, staging, and monitoring. Bayesian analysis dictates that if the prior probability of cancer is relatively low or if the consequences of a false-positive result are unacceptable, the test must be optimally specific. If the prior probability of cancer is high or if the consequences of missing it are unacceptable, the test must be optimally sensitive. For screening, the consequences of a miss are slight, and the consequences of labeling an insignificant cancer significant are serious. Thus, a very specific test is required. No current imaging modality fulfills this criterion. For staging, the prior probability of significant disease is relatively high, and the consequences of a miss serious, so a very sensitive test is required. Transrectal sonography, plus biopsy under sonographic control, fulfills this criterion for local disease, as does a bone scan for bone metastases. For monitoring, the prior probability is high, and the consequences of a miss serious, so a very sensitive test is needed. The bone scan is sensitive for bone metastases. Although CT is not sensitive for detecting lymph node metastases, it has practical clinical advantages over other imaging modalities for monitoring purposes in that it can detect disease in multiple structures at once. It is the only test that can monitor prostate size, the size of the lymph nodes, and whether hydronephrosis or liver metastases are present all in the scope of one examination.

Diagnostic Imaging↗

Ductal lavage findings in women with known breast cancer undergoing mastectomy.

BACKGROUND: Ductal lavage has the potential to detect cancer by sampling breast epithelium in asymptomatic high-risk women. To assess the utility of ductal lavage as a cancer diagnostic test, we investigated the association between ductal lavage cytologic findings and histologic findings in women with known breast cancer undergoing mastectomy. METHODS: Ductal lavage was performed in the operating room before mastectomy on 44 breasts from 32 women with known cancer and on eight breasts from seven women undergoing prophylactic mastectomy, two with occult malignancy. If the ductal lavage sample from one or more ducts contained enough epithelial cells for a cytologic diagnosis, lavaged ducts were injected with a mixture of colored dye, gelatin, and a radiographic contrast compound after mastectomy, and breast tissue was radiographed and sectioned. Histologic findings in ducts with and without dye were recorded. Associations between cytologic results and histologic results were examined by univariate and multivariable analyses. RESULTS: At least one duct was lavaged in 36 breasts (mean = 1.4 ducts per breast); all histologic and cytologic procedures were completed in 28 breasts and in 39 ducts. Markedly atypical or malignant cytology was found in five cancer-containing breasts. In 39 ducts with complete cytologic and histologic data and when marked atypia or malignant cells defined a positive cytologic test, sensitivity was 43% (95% confidence interval [CI] = 23% to 72%), specificity was 96% (95% CI = 86% to 100%), and accuracy was 77% (95% CI = 63% to 89%). When mild or marked atypia or malignant cells defined a positive cytologic test, sensitivity was 79% (95% CI = 57% to 96%), specificity was 64% (95% CI = 46% to 83%), and accuracy was 69% (95% CI = 55% to 83%). When all 31 cytologically evaluable breasts were analyzed, sensitivity was 17% (95% CI = 7% to 35%), specificity was 100% (95% CI = 5% to 100%), and accuracy was 19% (95% CI = 9% to 38%). CONCLUSION: In breasts with cancer, ductal lavage appears to have low sensitivity and high specificity for cancer detection, possibly because cancer-containing ducts fail to yield fluid or have benign or mildly atypical cytology.

Adult↗

[Tumor markers of breast cancer].

The most frequent cancer amongst women is that of the breast. Tumor markers may be helpful in the early diagnosis of breast cancer and the initial assessment of the extent of disease, as well as in monitoring tumor growth or volume reduction, and a recurrence of cancer. They have also been used for monitoring the clinical course of chemotherapy and radiotherapy. In this paper we focus on the role of tumor markers such as CA 15-3, CEA, and TPS in breast cancer diagnostics, including cytokines and molecular markers of carcinogenesis. We also show the prognostic significance of markers tested in breast cancer biopsies.

Biomarkers, Tumor↗

Cryptosporidiosis in children in a north Jordanian paediatric hospital.

We investigated the rate of infection by Cryptosporidium parvum among children from birth to 12 years attending Princess Rahma Teaching Hospital in Irbid, Jordan and evaluated various diagnostic methods. We collected single stool specimens from 300 children; 7 specimens were from children undergoing chemotherapy treatment for cancer. Diagnostic methods used for detection of infection were direct wet mount preparation, flotation concentration, cold Kinyoun Ziehl-Neelsen stain and direct immunofluorescence. We detected C. parvum oocysts in 112 samples (37.3%) using direct immunofluorescence, which showed the highest sensitivity. Source of drinking water appeared to be an important risk factor for transmission of infection. A higher incidence of infection was recorded during January-May, the rainy season.

Animals↗

Assessing oral cancer knowledge among dental students in South Carolina.

BACKGROUND: Because South Carolina has the fourth highest mortality rate for oral cancer among the 50 states, dental students in the state must be knowledgeable about prevention and early detection of the disease. METHODS: In 2002, the authors surveyed 163 students using a written questionnaire (response rate, 79.1 percent). The questionnaire included questions about oral cancer risk and nonrisk factors as well as oral cancer diagnostic signs, symptoms and examination procedures. The authors performed univariate and bivariate analyses (alpha < or = .025). RESULTS: At least 93 percent of the students replied that tobacco, alcohol and previous oral cancer lesions were risk factors. One hundred six students (65 percent) knew that the most likely site for oral cancer is the ventrolateral border of the tongue. Students differed in their overall knowledge of risk factors (P = .002), nonrisk factors (P < .001) and diagnostic procedures (P < .001). CONCLUSION: Although students' level of knowledge increased with academic year, educators and policy-makers need to place greater emphasis on oral cancer education and training in dental schools. PRACTICE IMPLICATIONS: Morbidity and mortality are likely to be reduced if dentists know how to prevent and detect oral cancer.

Adult↗

The diagnostic accuracy of Danish GPs in the diagnosis of pigmented skin lesions.

BACKGROUND: The GP often has a primary function in assessing pigmented skin lesions in Denmark. No data are available on the diagnostic accuracy of this process. OBJECTIVE: We aimed to study the sensitivity, specificity and positive prognostic value of the diagnosis made by 27 trained or trainee GPs. METHOD: We tested the diagnostic accuracy of the viewing of colour slides of pigmented skin lesions under standardized conditions at a seminar on skin cancer. Diagnostic accuracy was determined only for the clinically relevant diagnosis of benign or malignant. RESULTS: The median diagnostic accuracy (sensitivity) for the group as a whole was 0.75 (95% CI 0.65-0.80), the specificity was 0.70 (95% CI 0.68-0.79) and the positive predictive value 0.70 (95% CI 0.62-0.77). CONCLUSION: These values are comparable with previously published figures for trainee dermatologists, and it is therefore concluded that ongoing interest rather than basic training is the major determinant for clinical acumen.

Adult↗

Tiptoeing to chromosome tips: facts, promises and perils of today's human telomere biology.

The past decade has witnessed an explosion of knowledge concerning the structure and function of chromosome terminal structures-telomeres. Today's telomere research has advanced from a pure descriptive approach of DNA and protein components to an elementary understanding of telomere metabolism, and now to promising applications in medicine. These applications include 'passive' ones, among which the use of analysis of telomeres and telomerase (a cellular reverse transcriptase that synthesizes telomeres) for cancer diagnostics is the best known. The 'active' applications involve targeted downregulation or upregulation of telomere synthesis, either to mortalize immortal cancer cells, or to rejuvenate mortal somatic cells and tissues for cellular transplantations, respectively. This article reviews the basic data on structure and function of human telomeres and telomerase, as well as both passive and active applications of human telomere biology.

Aging↗

Cancer and older people.

This article considers some causes of cancer, diagnostic assessments and treatment options, as well as some of the myths surrounding the appropriate care of older people with cancer. It stresses the importance of employing the specialist knowledge of gerontological and cancer professionals in caring for the older person with cancer, and emphasises the central role of the nurse in delivering effective care.

Age Factors↗

Trends in colorectal cancer incidence and mortality in New South Wales, 1973-1992.

OBJECTIVE: To assess changes in incidence and mortality rates of colorectal cancer in different age groups in New South Wales (NSW) between 1973 and 1992. DESIGN: Descriptive analysis of data on incidence and mortality from the population-based NSW Central Cancer Registry and on colorectal cancer diagnostic tests from the Health Insurance Commission. MAIN OUTCOME MEASURES: Age-standardised incidence and mortality rates for colon and rectal cancer (defined by codes 153 and 154 in the International classification of diseases, 9th revision) by sex and age group (15-44, 45-59, 60-74 or > or = 75 years) and incidence by cancer spread at diagnosis; age-standardised rates for faecal occult blood tests, sigmoidoscopy and colonoscopy. RESULTS: From 1973 to 1992, colorectal cancer incidence increased significantly in NSW by an average of 2.0% per year in males (95% confidence interval [CI], 1.8 to 2.3) and 0.9% in females (95% CI, 0.7 to 1.1). Mortality rates remained nearly constant in males, but fell significantly in females by an average of -1.0% per year (95% CI, -1.3 to -0.7). In the youngest age group (15-44 years) both incidence and mortality rates fell significantly, while rates were stable or rose in older age groups, except for a significant fall in mortality in women aged > or = 75 years. Use of colonoscopy (an early detection method) increased, but a corresponding shift to detection of earlier-stage cancers was not seen. CONCLUSIONS: A reduction in risk factors and better treatment leading to longer survival may have contributed to the falls in incidence in younger people and in mortality in females.

Adolescent↗

[Early proteomics in ovarian cancer: myth or reality?].

Literature data summarizing new approaches and importance of early ovary cancer diagnostics have been reviewed. Alpha-feta-protein (AFP) and SA125 were the most reliable markers for determination of early ovary cancer stages. Nevertheless, these markers don't reflect the disease stage, malignance and they don't possess sufficient specificity. New methodical approaches have recently been introduced. They include combination of 2-D electrophoresis with mass-spectrometry. These methods allow to inventory and identify almost all proteins of various tissues. Using these methods for scanning proteins from biopsies of ovary cancer tissues new markers have been discovered.

Biomarkers, Tumor↗

Methyl selenium metabolites decrease prostate-specific antigen expression by inducing protein degradation and suppressing androgen-stimulated transcription.

Prostate-specific antigen (PSA) is widely used clinically for prostate cancer diagnostics and as an indicator of therapeutic efficacy and recurrence. Several human chemoprevention trials are being conducted to validate the prostate cancer prevention efficacy of selenium and PSA is used in these trials as a biomarker of response. A better understanding of the effects of selenium metabolites on the kinetics of PSA turnover and secretion in prostate cancer cells treated with selenium at concentrations which are achievable physiologically will be important for interpreting the results of these trials. This study addresses whether the putative active anticancer selenium metabolite methylselenol or its precursor methylseleninic acid (MSeA) specifically inhibits PSA expression in the androgen-responsive LNCaP prostate cancer cell model. The results show that exposure to sub-apoptotic concentrations of MSeA and methylselenol inhibited PSA protein expression and secretion, whereas sodium selenite and selenomethionine lacked inhibitory effect. The inhibition was detectable at 3 h of exposure and required a threshold level of MSeA to sustain. Turnover experiments showed that MSeA caused rapid PSA degradation, which was partially blocked by lysosomal inhibitors, but not by a proteasomal inhibitor. Furthermore, MSeA treatment reduced PSA mRNA level, down-regulated androgen receptor protein expression, and inhibited androgen-stimulated PSA promoter transcription. In summary, methylselenol or MSeA specifically and rapidly inhibited PSA expression through two mechanisms of action: inducing PSA protein degradation and suppressing androgen-stimulated PSA transcription. These findings may have important mechanistic implications for the prostate specific cancer chemopreventive action of selenium.

Androgens↗

Grading of gastric epithelial dysplasia. An interobserver study and analysis of diagnostic criteria.

One of the fundamental problems in the pathology of gastric epithelium is differentiation of reactive or regenerative proliferations, which are not precancerous from precancerous proliferations (i.e. dysplasia) and cancer. Diagnostic and interpretational difficulties, a need for a close cooperation between pathologists and clinicians and an attempt to more precisely assess gastric epithelial dysplasia prompted us to evaluate the usefulness of the current morphological criteria in the diagnosis and grading of gastric epithelial proliferations. The present study indicates that there are no sufficient grounds for grading of dysplasia, although the current morphological criteria permit establishment of a correct diagnosis. Therefore, the currently used three-grade classification of dysplasia may be successfully replaced with an easier two-grade classification or resigned totally.

Adult↗

Methylation assay for the diagnosis of lung cancer on bronchial aspirates: a cohort study.

PURPOSE: Recent studies have detected aberrant promoter methylation of adenomatous polyposis coli promoter 1 A (APC), cyclin-dependent kinase inhibitor-2A (p16(INK4a)), retinoic acid receptor beta2, and RAS association domain family protein 1 (RASSF1A) in bronchial aspirates and suggested their use as biomarkers for lung cancer diagnostics. The purpose of this study was to validate these candidate marker genes in a retrospective cohort study. EXPERIMENTAL DESIGN: Bronchial aspirates collected from a cohort comprising 247 patients with suspected lung cancer were investigated retrospectively regarding aberrant promoter methylation using a quantitative methylation-specific real-time PCR (QMSP). RESULTS: Eighty-nine patients were diagnosed with primary lung cancer, 102 had benign lung disease, and 56 showed miscellaneous other conditions. A panel consisting of APC, p16(INK4a), and RASSF1A emerged as useful combination. This panel detected aberrant methylation in bronchial aspirates of 22 of 35 (63%) and 21 of 44 (44%) centrally and peripherally located primary lung cancers, respectively. Bronchial aspirates also showed aberrant methylation in 5 of 7 (71%) patients with a recurrent lung cancer and in 8 of 30 (27%) cases without tumor recurrence. In contrast, only 1 of 102 patients with benign lung disease displayed a (false) positive test result. Rarely, aberrant methylation was found in patients with other malignancies (3 of 16). The QMSP assay correctly confirmed lung cancer in 8 of 12 (67%) cases with an ambiguous cytology. Moreover, it disclosed 9 of 26 (35%) of peripheral tumors lacking simultaneous cytologic or histologic diagnosis of malignancy. CONCLUSIONS: Our findings suggest that the QMSP assay could be applied as a reflex test in cases of suspected lung cancer that defy a definite diagnosis by conventional methods. Thus, the assay could be a useful diagnostic adjunct especially regarding peripheral tumors.

Adenomatous Polyposis Coli Protein↗

Purification and characterization of the mammaglobin/lipophilin B complex, a promising diagnostic marker for breast cancer.

Mammaglobin, a promising diagnostic marker for breast cancer, forms a covalent complex with lipophilin B. mRNA levels for each component of the complex were determined for a number of breast tumors and normal tissues, and correlation of message expression was highly significant between mammaglobin and lipophilin B (p < 0.0001). The complex was purified by both standard biochemical techniques and immunoaffinity chromatography. N-Terminal sequencing revealed that mammaglobin and lipophilin B are processed as predicted by cleavage of their signal sequence after amino acids 19 and 21, respectively. Three molecular masses-representing the fully glycosylated form, the complex without one of the carbohydrate chains, and the deglycosylated proteins-are detected by ProteinChip array SELDI-TOF mass spectrometry after partial enzymatic deglycosylation. This is consistent with the two predicted N-linked glycosylation sites in the primary sequence of mammaglobin and each site having an attached sugar of approximately 3500 Da. Reducing agents release lipophilin B from mammaglobin, and the free peptides are seen at their predicted molecular masses in the deglycosylated complex. Molecular modeling, secondary structure prediction, and circular dichroism indicate that the complex is a small alpha-helical globule that has three disulfide bridges and a carbohydrate chain at each pole. LC-ESI-MS shows that mammaglobin and lipophilin B are bonded in a head to tail orientation. This work describes the biochemistry of the mammaglobin/lipophilin B complex and lays the framework for use of this complex as a novel protein-based serological marker for breast cancer.

Adenocarcinoma↗

Cell-mediated immunity in prostatic cancer and its diagnostic relevancy.

Cell-mediated immunity (CMI) in prostatic cancer patients to presumptively identified prostatic tumour-associated antigens (TAA) was further evaluated in this study by tube leukocyte adherence inhibition in 504 patients with and without prostatic cancer. Peripheral blood leukocytes from 210 of 312 (67%) prostatic cancer patients possessed significant reactivity to extracts of malignant prostate. However, significant reactivity to malignant prostate was also observed in 89 of 192 (46%) controls comprised of patients with other than carcinoma of the prostate [including 91 patients with benign prostatic hypertrophy of which 46 (51%) possessed significant reactivity to malignant prostate] and healthy adults. With the exception of a significant difference in the reactivity between stage A vs stage C patients, there was no significant correlation between the level of reactivity to malignant prostate and the stage of disease. Had CMI to presumptively identified prostatic TAA been employed as an adjunctive diagnostic criterion to detect prostatic cancer, 191 (38%) of the 504 patients in this study would have been incorrectly diagnosed. The results of this study emphasize the critical need in attempting to delineate tumour-directed immunity from possible concomitant sensitization to tissue- and species-specific antigens for the identification, isolation and physicochemical characterization of what previously have been referred to as presumptively or putatively identified prostatic TAA.

Adenocarcinoma↗

Clinical proteomics and mass spectrometry profiling for cancer detection.

A key challenge in the clinical proteomics of cancer is the identification of biomarkers that would enable early detection, diagnosis and monitoring of disease progression to improve long-term survival of patients. Recent advances in proteomic instrumentation and computational methodologies offer a unique chance to rapidly identify these new candidate markers or pattern of markers. The combination of retentate affinity chromatography and mass spectrometry is one of the most interesting new approaches for cancer diagnostics using proteomic profiling. This review presents two technologies in this field, surface-enhanced laser desorption/ionization time-of-flight and Clinprot, and aims to summarize the results of studies obtained with the first of them for the early diagnosis of human cancer. Despite promising results, the use of the proteomic profiling as a diagnostic tool brought some controversies and technical problems, and still requires some efforts to be standardized and validated.

Biomarkers, Tumor↗

Methotrexate-modified superparamagnetic nanoparticles and their intracellular uptake into human cancer cells.

A magnetic nanoparticle conjugate was developed that can potentially serve both as a contrast enhancement agent in magnetic resonance imaging and as a drug carrier in controlled drug delivery, targeted at cancer diagnostics and therapeutics. The conjugate is made of iron oxide nanoparticles covalently bound with methotrexate (MTX), a chemotherapeutic drug that can target many cancer cells whose surfaces are overexpressed by folate receptors. The nanoparticles were first surface-modified with (3-aminopropyl)trimethoxysilane to form a self-assembled monolayer and subsequently conjugated with MTX through amidation between the carboxylic acid end groups on MTX and the amine groups on the particle surface. Drug release experiments demonstrated that MTX was cleaved from the nanoparticles under low pH conditions mimicking the intracellular conditions in the lysosome. Cellular viability studies in human breast cancer cells (MCF-7) and human cervical cancer cells (HeLa) further demonstrated the effectiveness of such chemical cleavage of MTX inside the target cells through the action of intracellular enzymes. The intracellular trafficking model proposed was supported through nanoparticle uptake studies which demonstrated that cells expressing the human folate receptor internalized a higher level of nanoparticles than negative control cells.

Animals↗