Chromogranin A: Is It a Useful Marker of Neuroendocrine Tumors?

2007 ◽  
Vol 25 (15) ◽  
pp. 1967-1973 ◽  
Author(s):  
Davide Campana ◽  
Francesca Nori ◽  
Lidya Piscitelli ◽  
Antonio Maria Morselli-Labate ◽  
Raffaele Pezzilli ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Plasma Levels ◽  
Chromogranin A ◽  
Imaging Techniques ◽  
High Specificity ◽  
Endocrine Tumors ◽  
Cell Hyperplasia ◽  
Specificity And Sensitivity ◽  
Ecl Cell ◽  
Number Of Patients

Purpose We evaluated the pattern of chromogranin A (CgA) plasma levels in a large number of patients with neuroendocrine tumors (NETs), in a series of patients with chronic atrophic gastritis (CAG) with and without enterochromaffin-like (ECL) cell hyperplasia, and in healthy participants (HPs). Patients and Methods Two hundred thirty-eight patients with NETs, 42 patients with CAG with or without ECL cell hyperplasia, and 48 HPs were studied. All patients underwent a baseline visit, biochemical routine check-up, imaging techniques, endoscopy, and histologic determination. Results CgA plasma levels were higher in patients with NETs compared with CAG patients or HPs (P < .001). In the NET group, we observed higher CgA levels in patients with diffuse disease compared with patients with local or hepatic disease (P < .001). CgA plasma levels were significantly higher in patients with Zollinger-Ellison syndrome compared with other types of endocrine tumors (P < .001). We found the best cutoff range between HPs and NET patients to be 18 to 19 U/L (sensitivity, 85.3%; specificity, 95.8%). Comparing all participants without neoplasia (HPs, CAG patients, and disease-free patients) and patients with endocrine tumors, the best cutoff range was 31 to 32 U/L (sensitivity, 75.3%; specificity, 84.2%). Setting the specificity at 95%, the cutoff range was 84 to 87 U/L (sensitivity, 55%). Conclusion Our study confirms the high specificity and sensitivity of CgA in diagnosing an endocrine tumor. It is necessary to use a cutoff range of 84 to 87 U/L to obtain a high specificity in diagnosing NETs, with the aim of excluding patients in whom the CgA was elevated as a result of other non-neoplastic diseases.

Diagnostic Accuracy of a New d-Dimer Assay (Sclavo Auto d-Dimer) for Exclusion of Deep Vein Thrombosis in Symptomatic Outpatients

2016 ◽  
Vol 23 (3) ◽  
pp. 221-228 ◽  
Author(s):  
Cristina Legnani ◽  
Michela Cini ◽  
Mirella Frascaro ◽  
Giuseppina Rodorigo ◽  
Michelangelo Sartori ◽  
...  
Keyword(s):  
Deep Vein Thrombosis ◽  
Imaging Techniques ◽  
False Negative ◽  
High Specificity ◽  
Predictive Values ◽  
Cutoff Value ◽  
Vein Thrombosis ◽  
Number Of Patients ◽  
Deep Vein ◽  
D Dimer

In patients presenting non-high clinical pretest probability (PTP), a negative d-dimer can exclude venous thromboembolism without imaging tests. However, each d-dimer assay should be validated in prospective studies. We evaluated an automated d-dimer immunoassay using the Sclavo Auto d-dimer (Sclavo Diagnostics Int, Sovicille, Italy) provided by Dasit Diagnostica (Cornaredo, Milan, Italy). Three hundred two consecutive outpatients suspected of leg deep vein thrombosis (DVT) with non-high PTP were included. The Sclavo Auto d-dimer assay was evaluated on 2 analyzers (Sysmex CA-7000 and Sysmex CS-2100; Sysmex Corporation, Kobe, Japan, provided by Dasit). The cutoff value (200 ng/mL) was established a priori. Prevalence of DVT was 11.9%. Since no false-negative patients were detected, the sensitivity and negative predictive values (NPVs) were 100% (sensitivity = CA-7000: 100% [95% confidence interval, CI: 93.3-100], CS-2100: 100% [95% CI: 93.3-100]; NPV = CA-7000: 100% [95% CI: 97.9-100], CS-2100: 100% [95% CI: 98.0-100]). Specificity was 65.4% (95% CI: 59.4-71.1) and 69.2% (95% CI: 63.3-74.7) for CA-7000 and CS-2100, respectively. Specificity increased when a higher cutoff value (234 ng/mL) was used for patients aged ≥60 years without compromising the safety. Assay reproducibility was satisfactory at concentrations near the cutoff value (total coefficient of variations <10%). In conclusion, the Sclavo Auto d-dimer assay was accurate when used for DVT diagnostic workup in outpatients with non-high PTP. Based on its high sensitivity and NPV, it can be used as a stand-alone test in outpatients with non-high PTP. Given its high specificity, the number of patients in whom further imaging techniques can be avoided increased, improving the yield of the test.

scholarly journals Radiolabelled Aptamers for Theranostic Treatment of Cancer

2018 ◽  
Vol 12 (1) ◽  
pp. 2 ◽  
Author(s):  
Umair Khalid ◽  
Chris Vi ◽  
Justin Henri ◽  
Joanna Macdonald ◽  
Peter Eu ◽  
...  
Keyword(s):  
Binding Affinity ◽  
High Specificity ◽  
Cancer Diagnostics ◽  
Molecular Biomarker ◽  
Specificity And Sensitivity ◽  
Number Of Patients ◽  
Incidence And Mortality ◽  
High Incidence ◽  
High Binding Affinity ◽  
As Toxicity

Cancer has a high incidence and mortality rate worldwide, which continues to grow as millions of people are diagnosed annually. Metastatic disease caused by cancer is largely responsible for the mortality rates, thus early detection of metastatic tumours can improve prognosis. However, a large number of patients will also present with micrometastasis tumours which are often missed, as conventional medical imaging modalities are unable to detect micrometastases due to the lack of specificity and sensitivity. Recent advances in radiochemistry and the development of nucleic acid based targeting molecules, have led to the development of novel agents for use in cancer diagnostics. Monoclonal antibodies may also be used, however, they have inherent issues, such as toxicity, cost, unspecified binding and their clinical use can be controversial. Aptamers are a class of single-stranded RNA or DNA ligands with high specificity, binding affinity and selectivity for a target, which makes them promising for molecular biomarker imaging. Aptamers are presented as being a superior choice over antibodies because of high binding affinity and pH stability, amongst other factors. A number of aptamers directed to cancer cell markers (breast, lung, colon, glioblastoma, melanoma) have been radiolabelled and characterised to date. Further work is ongoing to develop these for clinical applications.

scholarly journals Fast fluorescence lifetime imaging techniques: A review on challenge and development

2019 ◽  
Vol 12 (05) ◽  
pp. 1930003 ◽  
Author(s):  
Xiongbo Liu ◽  
Danying Lin ◽  
Wolfgang Becker ◽  
Jingjing Niu ◽  
Bin Yu ◽  
...  
Keyword(s):  
Fluorescence Lifetime ◽  
Imaging Techniques ◽  
Complex Function ◽  
High Specificity ◽  
Acquisition Time ◽  
Maximum Speed ◽  
Fluorescence Lifetime Imaging ◽  
Lifetime Imaging ◽  
Specificity And Sensitivity ◽  
Cellular Microenvironments

Fluorescence lifetime imaging microscopy (FLIM) is increasingly used in biomedicine, material science, chemistry, and other related research fields, because of its advantages of high specificity and sensitivity in monitoring cellular microenvironments, studying interaction between proteins, metabolic state, screening drugs and analyzing their efficacy, characterizing novel materials, and diagnosing early cancers. Understandably, there is a large interest in obtaining FLIM data within an acquisition time as short as possible. Consequently, there is currently a technology that advances towards faster and faster FLIM recording. However, the maximum speed of a recording technique is only part of the problem. The acquisition time of a FLIM image is a complex function of many factors. These include the photon rate that can be obtained from the sample, the amount of information a technique extracts from the decay functions, the efficiency at which it determines fluorescence decay parameters from the recorded photons, the demands for the accuracy of these parameters, the number of pixels, and the lateral and axial resolutions that are obtained in biological materials. Starting from a discussion of the parameters which determine the acquisition time, this review will describe existing and emerging FLIM techniques and data analysis algorithms, and analyze their performance and recording speed in biological and biomedical applications.

scholarly journals Plasma chromogranin A in patients with autoimmune chronic atrophic gastritis, enterochromaffin-like cell lesions and gastric carcinoids

2005 ◽  
Vol 152 (3) ◽  
pp. 443-448 ◽  
Author(s):  
M Peracchi ◽  
C Gebbia ◽  
G Basilisco ◽  
M Quatrini ◽  
C Tarantino ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Healthy Subjects ◽  
Chromogranin A ◽  
Neuroendocrine Tumours ◽  
Chronic Atrophic Gastritis ◽  
Cell Hyperplasia ◽  
Gastric Carcinoids ◽  
Ecl Cell ◽  
Design And Methods

Objective: In atrophic body gastritis (ABG) chronic hypergastrinaemia stimulates enterochromaffin-like (ECL) cell proliferation with development of cell hyperplasia, dysplasia and possibly type-1 gastric carcinoids. As circulating chromogranin A (CgA) levels are a marker of neuroendocrine tumours, we evaluated the clinical usefulness of CgA assay in ABG patients to detect those with carcinoids. Design and methods: Plasma CgA levels were measured using a commercial ELISA in 45 healthy volunteers, nine patients with type-1 gastric carcinoids and 43 consecutive ABG patients (21 without and 22 with ECL cell hyperplasia/dysplasia). Results: CgA levels were significantly higher in ABG patients with and without gastric carcinoids than in healthy subjects (P < 0.001). The highest values occurred in patients with carcinoids (median (interquartile range): 58.1 (44.5–65.3) U/l) and with ECL cell hyperplasia/dysplasia (35.5 (31.8–48.65) U/l) but there were no significant differences in CgA among the various subgroups of ABG patients classified according to ECL cell status. Nevertheless, in ABG patients without carcinoids CgA values correlated with the presence and severity of ECL cell lesions (r s = 0.428, P < 0.01). The sensitivity and specificity of the CgA assay in identifying patients with carcinoids were 100 and 23% respectively. Conclusions: CgA plasma levels reflect the histological degree of ECL cell lesions in patients with ABG but the assay specificity is too low to detect among these patients those with gastric carcinoids.

Accuracy and Clinical Correlates of Two Different Methods for Chromogranin A Assay in Neuroendocrine Tumors

2004 ◽  
Vol 19 (4) ◽  
pp. 295-304 ◽  
Author(s):  
L. Ferrari ◽  
E. Seregni ◽  
G. Lucignani ◽  
E. Bajetta ◽  
A. Martinetti ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Chromogranin A ◽  
Enzyme Linked Immunosorbent Assay ◽  
Roc Curve Analysis ◽  
Pancreatic Islet Cell ◽  
Tumor Histology ◽  
Specificity And Sensitivity ◽  
Clinical Accuracy ◽  
Pancreatic Islet Cell Tumors ◽  
Rapid Hydrolysis

Measurement of chromogranin A (CgA) plays a major role in the management of neuroendocrine tumors (NET); however, reliable assaying of CgA is made difficult by the rapid hydrolysis following its release into the bloodstream. This study was aimed at the assessment of two assays for CgA in NET patients. CgA was measured in 93 patients by means of an enzyme-linked immunosorbent assay (ELISA) and an immunoradiometric assay (IRMA). The specificity and sensitivity of CgA were evaluated in relation to tumor histology. The clinical accuracy of the two assays was evaluated by receiver-operating characteristic (ROC) curve analysis. Regression analysis demonstrated different immunoreactivity for CgA of the antibodies used in the two kits (r=0.61). The two assays had different accuracy also in classifying patients according to their clinical condition (91% vs 64% specificity and 79% vs 79% sensitivity for the ELISA and IRMA assay, respectively) and tumor histology (81% vs 85% sensitivity for the ELISA and IRMA assays, respectively, in carcinoids; 92% vs 67% sensitivity for the ELISA and IRMA assays, respectively, in pancreatic islet cell tumors). The different clinical accuracy of the two assays was confirmed by the ROC analysis (AUC=0.90 vs AUC=0.87 for the ELISA and IRMA assays, respectively). In conclusion, because of the poor standardization of the commercially available measurement tools the clinical accuracy of CgA measurement depends on the assay used. This makes it difficult to compare CgA values measured with different kits and affects the clinical accuracy of the different assays for CgA.

scholarly journals Melanoma Biomarkers and Their Potential Application for In Vivo Diagnostic Imaging Modalities

2020 ◽  
Vol 21 (24) ◽  
pp. 9583
Author(s):  
Monica Hessler ◽  
Elmira Jalilian ◽  
Qiuyun Xu ◽  
Shriya Reddy ◽  
Luke Horton ◽  
...  
Keyword(s):  
Imaging Modality ◽  
Imaging Techniques ◽  
High Specificity ◽  
Diagnostic Challenge ◽  
Skin Imaging ◽  
Non Invasive ◽  
Dermatology Clinic ◽  
Melanoma Diagnosis ◽  
Specificity And Sensitivity

Melanoma is the deadliest form of skin cancer and remains a diagnostic challenge in the dermatology clinic. Several non-invasive imaging techniques have been developed to identify melanoma. The signal source in each of these modalities is based on the alteration of physical characteristics of the tissue from healthy/benign to melanoma. However, as these characteristics are not always sufficiently specific, the current imaging techniques are not adequate for use in the clinical setting. A more robust way of melanoma diagnosis is to “stain” or selectively target the suspect tissue with a melanoma biomarker attached to a contrast enhancer of one imaging modality. Here, we categorize and review known melanoma diagnostic biomarkers with the goal of guiding skin imaging experts to design an appropriate diagnostic tool for differentiating between melanoma and benign lesions with a high specificity and sensitivity.

Pre-operative Diagnosis of Pancreatic Neuroendocrine Tumors with Endoscopic Ultrasonography and Computed Tomography in a Large Series

2016 ◽  
Vol 25 (3) ◽  
pp. 317-321 ◽  
Author(s):  
Raffaele Manta ◽  
Elisabetta Nardi ◽  
Nico Pagano ◽  
Claudio Ricci ◽  
Mariano Sica ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Neuroendocrine Tumors ◽  
Endoscopic Ultrasonography ◽  
Fine Needle Aspiration ◽  
Chromogranin A ◽  
Needle Aspiration ◽  
Large Series ◽  
Tumor Diameter ◽  
Pancreatic Neuroendocrine Tumors ◽  
Fine Needle

Background & Aims: Diagnosis of pancreatic neuroendocrine tumors (p-NETs) is frequently challenging. We describe a large series of patients with p-NETs in whom both pre-operative Computed Tomography (CT) and Endoscopic Ultrasonography (EUS) were performed. Methods: This was a retrospective analysis of prospectively collected sporadic p-NET cases. All patients underwent both standard multidetector CT study and EUS with fine-needle aspiration (FNA). The final histological diagnosis was achieved on a post-surgical specimen. Chromogranin A (CgA) levels were measured. Results: A total of 80 patients (mean age: 58 ± 14.2 years; males: 42) were enrolled. The diameter of functioning was significantly lower than that of non-functioning p-NETs (11.2 ± 8.5 mm vs 19.8 ± 12.2 mm; P = 0.0004). The CgA levels were more frequently elevated in non-functioning than functioning pNET patients (71.4% vs 46.9%; P = 0.049). Overall, the CT study detected the lesion in 51 (63.7%) cases, being negative in 26 (68.4%) patients with a tumor ≤10 mm, and in a further 3 (15%) cases with a tumor diameter ≤20 mm. CT overlooked the pancreatic lesion more frequently in patients with functioning than non-functioning p-NETs (46.5% vs 24.3%; P = 0.002). EUS allowed a more precise pre-operative tumor measurement, with an overall incorrect dimension in only 9 (11.2%) patients. Of note, the EUS-guided FNA suspected the neuroendocrine nature of tumor in all cases. Conclusions: Data of this large case series would suggest that the EUS should be included in the diagnostic work-up in all patients with a suspected p-NET, even when the CT study was negative for a primary lesion in the pancreas.– . Abbrevations: CgA: chromogranin A; EUS: Endoscopic Ultrasonography; FNA: fine-needle aspiration; p-NETs: pancreatic neuroendocrine tumors.

Prospective Application of Aptamer-based Assays and Therapeutics in Bloodstream Infections

2020 ◽  
Vol 20 (10) ◽  
pp. 831-840
Author(s):  
Weibin Li
Keyword(s):  
Pathogenic Bacteria ◽  
Genetic Diagnosis ◽  
Bloodstream Infections ◽  
High Specificity ◽  
Peptide Sequence ◽  
High Morbidity ◽  
Specificity And Sensitivity ◽  
Prospective Application ◽  
Small Molecule Therapeutics

Sepsis is still a severe health problem worldwide with high morbidity and mortality. Blood bacterial culture remains the gold standard for the detection of pathogenic bacteria in bloodstream infections, but it is time-consuming, and both the sophisticated equipment and well-trained personnel are required. Immunoassays and genetic diagnosis are expensive and limited to specificity and sensitivity. Aptamers are single-stranded deoxyribonucleic acid (ssDNA) and ribonucleic acid (RNA) oligonucleotide or peptide sequence generated in vitro based on the binding affinity of aptamer-target by a process known as Systematic Evolution of Ligands by Exponential Enrichment (SELEX). By taking several advantages over monoclonal antibodies and other conventional small-molecule therapeutics, such as high specificity and affinity, negligible batch-to-batch variation, flexible modification and production, thermal stability, low immunogenicity and lack of toxicity, aptamers are presently becoming promising novel diagnostic and therapeutic agents. This review describes the prospective application of aptamerbased laboratory diagnostic assays and therapeutics for pathogenic bacteria and toxins in bloodstream infections.

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