scholarly journals The Diagnostic Accuracy of Mutant KRAS Detection from Pancreatic Secretions for the Diagnosis of Pancreatic Cancer: A Meta-Analysis

Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2353
Author(s):  
Nikhil Patel ◽  
Tatjana Petrinic ◽  
Michael Silva ◽  
Zahir Soonawalla ◽  
Srikanth Reddy ◽  
...  
Keyword(s):  
Chronic Pancreatitis ◽  
Diagnostic Accuracy ◽  
Kras Mutation ◽  
Meta Analysis ◽  
Ductal Adenocarcinoma ◽  
Healthy Individuals ◽  
Kras Mutations ◽  
Cross Sectional ◽  
Specificity And Sensitivity ◽  
Variable Sensitivity

This meta-analysis aims to identify the diagnostic accuracy of mutations in the Kirsten Rat Sarcoma (KRAS) oncogene in the diagnosis of pancreatic ductal adenocarcinoma (PDAC). The survival of PDAC remains poor often due to the fact that disease is advanced at diagnosis. We analysed 22 studies, with a total of 2156 patients, to identify if the detection of KRAS mutations from pancreatic exocrine secretions yields sufficient specificity and sensitivity to detect patients with PDAC amongst healthy individuals. The majority of the studies were retrospective, samples were obtained endoscopically or surgically, and included comparator populations of patients with chronic pancreatitis and pre-malignant pancreatic lesions (PanIN) as well as healthy controls. We performed several analyses to identify the diagnostic accuracy for PDAC among these patient populations. Our results highlighted that the diagnostic accuracy of KRAS mutation for PDAC was of variable sensitivity and specificity when compared with PanINs and chronic pancreatitis, but had a higher specificity among healthy individuals. The sensitivity of this test must be improved to prevent missing early PDAC or PanINs. This could be achieved with rigorous prospective cohort studies, in which high-risk patients with normal cross-sectional imaging undergo surveillance following KRAS mutation testing.

scholarly journals A Circulating Exosome RNA Signature Is a Potential Diagnostic Marker for Pancreatic Cancer, a Systematic Study

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2565
Author(s):  
Yixing Wu ◽  
Hongmei Zeng ◽  
Qing Yu ◽  
Huatian Huang ◽  
Beatrice Fervers ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Chronic Pancreatitis ◽  
Early Detection ◽  
Validation Dataset ◽  
Healthy Controls ◽  
Rna Seq ◽  
Healthy Individuals ◽  
Kras Mutations ◽  
Significant Difference ◽  
Rna Signature

Several exosome proteins, miRNAs and KRAS mutations have been investigated in the hope of carrying out the early detection of pancreatic cancer with high sensitivity and specificity, but they have proven to be insufficient. Exosome RNAs, however, have not been extensively evaluated in the diagnosis of pancreatic cancer. The purpose of this study was to investigate the potential of circulating exosome RNAs in pancreatic cancer detection. By retrieving RNA-seq data from publicly accessed databases, differential expression and random-effects meta-analyses were performed. The results showed that pancreatic cancer had a distinct circulating exosome RNA signature in healthy individuals, and that the top 10 candidate exosome RNAs could distinguish patients from healthy individuals with an area under the curve (AUC) of 1.0. Three (HIST2H2AA3, LUZP6 and HLA-DRA) of the 10 genes in exosomes had similar differential patterns to those in tumor tissues based on RNA-seq data. In the validation dataset, the levels of these three genes in exosomes displayed good performance in distinguishing cancer from both chronic pancreatitis (AUC = 0.815) and healthy controls (AUC = 0.8558), whereas a slight difference existed between chronic pancreatitis and healthy controls (AUC = 0.586). Of the three genes, the level of HIST2H2AA3 was positively associated with KRAS status. However, there was no significant difference in the levels of the three genes across the disease stages (stages I–IV). These findings indicate that circulating exosome RNAs have a potential early detection value in pancreatic cancer, and that a distinct exosome RNA signature exists in distinguishing pancreatic cancer from healthy individuals.

Diagnostic accuracy of centralised assays for TB detection and detection of resistance to rifampicin and isoniazid: a systematic review and meta-analysis

2020 ◽  
Vol 57 (2) ◽  
pp. 2000747
Author(s):  
Mikashmi Kohli ◽  
Emily MacLean ◽  
Madhukar Pai ◽  
Samuel G. Schumacher ◽  
Claudia M. Denkinger
Keyword(s):  
Systematic Review ◽  
Diagnostic Accuracy ◽  
Meta Analysis ◽  
Tracheal Aspirate ◽  
Rifampicin Resistance ◽  
Isoniazid Resistance ◽  
Cross Sectional ◽  
Molecular Assays ◽  
Index Tests ◽  
Resistance Detection

Various diagnostic companies have developed high throughput molecular assays for tuberculosis (TB) and resistance detection for rifampicin and isoniazid. We performed a systematic review and meta-analyses to assess the diagnostic accuracy of five of these tests for pulmonary specimens. The tests included were Abbott RealTime MTB, Abbott RealTime RIF/INH, FluoroType MTB, FluoroType MTDBR and BD Max MDR-TB assay.A comprehensive search of six databases for relevant citations was performed. Cross-sectional, case-control, cohort studies, and randomised controlled trials of any of the index tests were included. Respiratory specimens (such as sputum, bronchoalveolar lavage, tracheal aspirate, etc.) or their culture isolates.A total of 21 included studies contributed 26 datasets. We could only meta-analyse data for three of the five assays identified, as data were limited for the remaining two. For TB detection, the included assays had a sensitivity of 91% or more and the specificity ranged from 97% to 100%. For rifampicin resistance detection, all the included assays had a sensitivity of more than 92%, with a specificity of 99–100%. Sensitivity for isoniazid resistance detection varied from 70 to 91%, with higher specificity of 99–100% across all index tests. Studies that included head-to-head comparisons of these assays with Xpert MTB/RIF for detection of TB and rifampicin resistance suggested comparable diagnostic accuracy.In people with symptoms of pulmonary TB, the centralised molecular assays demonstrate comparable diagnostic accuracy for detection of TB, rifampicin and isoniazid resistance to Xpert MTB/RIF assay, a WHO recommended molecular test.

scholarly journals Prognostic Implications of Multiplex Detection of KRAS Mutations in Cell-Free DNA from Patients with Pancreatic Ductal Adenocarcinoma

2018 ◽  
Vol 64 (4) ◽  
pp. 726-734 ◽  
Author(s):  
Min Kyeong Kim ◽  
Sang Myung Woo ◽  
Boram Park ◽  
Kyong-Ah Yoon ◽  
Yun-Hee Kim ◽  
...  
Keyword(s):  
Kras Mutation ◽  
Progression Free Survival ◽  
Ductal Adenocarcinoma ◽  
Multiplex Detection ◽  
Kras Mutations ◽  
Cell Free Dna ◽  
Free Survival ◽  
Free Dna ◽  
Fractional Abundance ◽  
Prognostic Implications

Abstract BACKGROUND Cell-free DNA (cfDNA) is known to provide potential biomarkers for predicting clinical outcome, but its value in pancreatic ductal adenocarcinoma (PDAC) has not been fully evaluated. The aim of this study was to evaluate the clinical applicability of quantitative analysis of multiplex KRAS mutations in cell-free DNA from patients with PDAC. METHODS A total of 106 patients with PDAC were enrolled in this prospective study. The concentration and fraction of KRAS mutations were determined through multiplex detection of KRAS mutations in plasma samples by use of a droplet digital PCR kit (Bio-Rad). RESULTS KRAS mutations were detected in 96.1% of tissue samples. Eighty patients (80.5%) harbored KRAS mutations in cfDNA, with a median KRAS mutation concentration of 0.165 copies/μL and a median fractional abundance of 0.415%. Multivariable analyses demonstrated that the KRAS mutation concentration [hazard ratio (HR), 2.08; 95% CI, 1.20–3.63] and KRAS fraction (HR, 1.73; 95% CI, 1.02–2.95) were significant factors for progression-free survival. KRAS mutation concentration (HR, 1.97; 95% CI, 1.05–3.67) also had prognostic implications for overall survival. Subgroup analyses showed that KRAS mutation concentration and fractional abundance significantly affected progression-free survival in resectable PDAC (P = 0.016). Moreover, when combined with the cancer biomarker CA19-9, the KRAS mutation concentration in cfDNA showed additive benefits for the prediction of overall survival. CONCLUSIONS This study demonstrates that multiplex detection of KRAS mutations in plasma cfDNA is clinically relevant, providing a potential candidate biomarker for prognosis of PDAC.

scholarly journals Frequency of K-ras Mutations in Pancreatic Intraductal Neoplasias Associated with Pancreatic Ductal Adenocarcinoma and Chronic Pancreatitis: A Meta-Analysis

Neoplasia ◽  
2005 ◽  
Vol 7 (1) ◽  
pp. 17-23 ◽  
Author(s):  
Matthias Löhr ◽  
Gunter Klöppel ◽  
Patrick Maisonneuve ◽  
Albert B. Lowenfels ◽  
Jutta Lüttges
Keyword(s):  
Chronic Pancreatitis ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Meta Analysis ◽  
Ductal Adenocarcinoma ◽  
Ras Mutations

scholarly journals Diagnostic Accuracy of COVID-19 Antibody Tests Authorized by FDA Philippines: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 3 (4) ◽  
pp. 283-301
Author(s):  
Carmel Reina R. Chua ◽  
Esther Delle E. De los Santos ◽  
Karla Veronica H. Escasa ◽  
Richmond Louis G. Estolas ◽  
Junnealyn Feliciano ◽  
...  
Keyword(s):  
Systematic Review ◽  
Diagnostic Accuracy ◽  
Random Effects ◽  
Meta Analysis ◽  
Characteristic Curve ◽  
Enzyme Linked Immunosorbent Assay ◽  
Serological Tests ◽  
Random Effects Models ◽  
Specificity And Sensitivity ◽  
Antibody Tests

Introduction: Coronavirus Disease (COVID-19) is a highly infectious disease caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) which has infected many people all over the world. One of the best ways to lessen its spread is through early detection and diagnosis. Various serological tests are now being used as a surveillance tool in the detection of antibodies as a response to SARS-CoV-2. The aim of this study is to evaluate the diagnostic accuracy and performance of the available COVID-19 antibody tests authorized by the Food and Drug Administration (FDA) Philippines that make use of Enzyme-Linked Immunosorbent Assay (ELISA), Chemiluminescence Immunoassay (CLIA) and Lateral Flow Immunoassay (LFIA). Method: Complete published journal articles relevant to the diagnostic accuracy of the three antibody tests were collected using trusted medical journal search engines. The quality of journals was assessed using QUADAS-2 to determine the risk of bias and assess the applicability judgments of diagnostic accuracy studies. Forest plots were used to summarize the performance of LFIA, ELISA and CLIA according to their specificity and sensitivity in detecting various antibodies. Pooled sensitivity and specificity were also done using bivariate random-effects models with its log-likelihood, a corresponding chi-square test statistic, and area under the summary Receiver-Operating Characteristic curve to see the potential heterogeneity in the data and to assess the diagnostic accuracy of the COVID-19 antibody tests. Results: Bivariate random-effects model and areas under the sROC curve were used to evaluate the diagnostic accuracy of COVID-19 antibody tests. The pooled sensitivity in detecting IgG based on CLIA, ELISA, and LFIA were 81.7%, 58.7%, and 74.3% respectively, with an overall of 72.0%. For IgM detection, LFIA has a higher pooled sensitivity of 69.6% than CLIA with 61.0%. Overall, the pooled sensitivity is 68.5%. In IgA detection, only ELISA based test was included with a pooled sensitivity of 84.8%. Lastly, pooled sensitivities for combined antibodies based on ELISA and LFIA were 89.0% and 81.6% respectively, with an overall of 82.5%. On the other hand, all tests excluding ELISA-IgA displayed high pooled specificities with a range of 94.0% to 100.0%. Diagnostic accuracies of the test in detecting IgG, IgM, and combined antibodies were found out to be almost perfect based on the computed area under the sROC with values of 0.973, 0.953, and 0.966, respectively. Conclusion: In this systematic review and meta-analysis, existing evidence on the diagnostic accuracy of antibody tests for COVID-19 were found to be characterized by high risks of bias, consistency in the heterogeneity of sensitivities, and consistency in the homogeneity of high specificities except in IgA detection using ELISA. The bivariate random-effects models showed that there are no significant differences in terms of sensitivity among CLIA, ELISA and LFIA in detecting IgG, IgM, and combined antibodies at a 95% confidence interval. Nonetheless, CLIA, ELISA and LFIA were found to have excellent diagnostic accuracies in the detection of IgG, IgM and combined antibodies as reflected by their AUC values. Doi: 10.28991/SciMedJ-2021-0304-1 Full Text: PDF

scholarly journals Diagnostic accuracy of D-dimer to detect left atrial thrombus in patients with atrial fibrillation: a systematic review and meta-analysis

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
C Diaz-Arocutipa ◽  
A.C Gonzales-Luna ◽  
A Branez-Condorena ◽  
A.V Hernandez
Keyword(s):  
Atrial Fibrillation ◽  
Diagnostic Accuracy ◽  
Left Atrial ◽  
Meta Analysis ◽  
Characteristic Curve ◽  
Left Atrial Thrombus ◽  
Summary Receiver Operating Characteristic ◽  
Atrial Thrombus ◽  
Cross Sectional ◽  
D Dimer

Abstract Background There is limited evidence on the use of biomarkers to diagnose left atrial thrombus in atrial fibrillation. Purpose We evaluated the diagnostic accuracy of D-dimer to detect left atrial thrombus in patients with atrial fibrillation. Methods We searched four electronic databases from inception to December 16, 2020 for observational studies evaluating diagnostic accuracy of D-dimer. Reference standard was left atrial thrombus detected by transesophageal echocardiography. Study quality was assessed with the QUADAS-2 tool. We performed a bivariate random-effects meta-analysis to calculate the pooled sensitivity and specificity with their 95% confidence intervals (95% CI). In addition, a summary receiver operating characteristic curve and optimal cut-off were estimated. Results Eleven cross-sectional studies involving 4380 patients were included. The mean age ranged from 49.8 to 74.1 years and 70% of patients were men. Left atrial thrombus was present in 7% of cases. In seven studies, the pooled sensitivity of D-dimer at 500 ng/mL was 53% (95% CI, 26–79%) and the pooled specificity was 92% (95% CI, 80–97%). The pooled sensitivity of age-adjusted D-dimer was 35% (95% CI, 18–57%) and the pooled specificity was 100% (95% CI, 100–100%) in two studies. The optimal cut-off was 390 ng/mL in 10 studies with a pooled sensitivity of 68% (95% CI, 44–85%) and a pooled specificity of 73% (95% CI, 54–86%). The risk of bias was low or unclear for all domains. Concerns regarding applicability were generally low for almost all studies Conclusion Our meta-analysis suggests that D-dimer has the potential to be useful to the detection of left atrial thrombus in patients with atrial fibrillation. FUNDunding Acknowledgement Type of funding sources: None.

scholarly journals Diagnostic Accuracy of Hysterosonography in Diagnosis of Uterine Lesions by Taking Hysteroscopy as Gold Standard

2021 ◽  
Vol 15 (7) ◽  
pp. 1902-1905
Author(s):  
Farah Naz ◽  
Adnan Ahmed ◽  
Samina Shaikh ◽  
Hafeez ur Rehman ◽  
Tahir Baig ◽  
...  
Keyword(s):  
Diagnostic Accuracy ◽  
Gold Standard ◽  
Pregnancy Loss ◽  
Recurrent Pregnancy Loss ◽  
Diagnostic Technique ◽  
Reproductive Age ◽  
Transvaginal Sonography ◽  
Cross Sectional ◽  
Reproductive Age Women ◽  
Specificity And Sensitivity

Background and Aim: Evaluation of uterine abnormalities is infertility core partto be assessed in impaired reproduction cases. Uterine abnormalities can be assessed by various radiological imaging modalities such as transvaginal sonography, hysterosalpingography and hysterosonography. The current study aims to evaluate the diagnostic accuracy of hysterosonography in diagnosis of uterine lesions by taking hysteroscopy as gold standard. Materials and Methods: This observation-based cross-sectional study was carried out on 108 reproductive-age women at the Department of Obstetrics and Gynecology of Liaquat University of Medical and Health Sciences, Jamshoro during the period from January 2020 to June 2020.These women had uterine abnormalities such as recurrent pregnancy loss, abnormal uterine bleeding, infertility, and clinically diagnosed lesions of intrauterine. All individuals underwent hysteroscopy evaluation.Global sensitivity analysis technique was used to calculate the bias-adjusted specificity and sensitivity of hysterosonography. Uterine abnormalities were assessed by hysteroscopy taking it as a gold standard. SPSS version 20 was used for data analysis. Results:The mean age of the women was 27.3 ± 5.63 with age range 20 to 34 years and parity ranged from 0 to 5. Out of 108 patients, 49 (45.4%) had positive findings of abnormal uterine lesions including myomas in 13 (12.3%), polyps 17 (15.7%), uterine septum 7 (6.4%) and intrauterine adhesions 12 (11.1%). Among all, forty-nine (45.4%) women had infertility, previous cesarean section 20 (19.1%), recurrent pregnancy loss 18 (16.6%), and menstrual disorders 21 (19.4%).Diagnostic accuracy of hysterosonography in terms of specificity, sensitivity, and Positive prediction value (PPV) was 94%, 77%, and 74% for uterine lesions respectively while taking hysteroscopy as a gold standard. Conclusion: The present study concluded that uterine lesions among reproductive-age women could be easily assessed with higher accuracy of hysterosonography. Based on the specificity and sensitivity of hysteroscopy as a gold standard for hysterosonography is the most reliable, safe and accurate diagnostic technique for uterine lesions. Keywords:Hysterosonography, Uterine lesions

scholarly journals Meta-Analysis of Circulating Cell-Free DNA’s Role in the Prognosis of Pancreatic Cancer

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3378
Author(s):  
Jelena Milin-Lazovic ◽  
Petar Madzarevic ◽  
Nina Rajovic ◽  
Vladimir Djordjevic ◽  
Nikola Milic ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Meta Analysis ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Ductal Adenocarcinoma ◽  
Cochrane Library ◽  
Molecular Characteristics ◽  
Kras Mutations ◽  
Additional Tool ◽  
Number Of Patients

Introduction: The analysis of cell-free DNA (cfDNA) for genetic abnormalities is a promising new approach for the diagnosis and prognosis of pancreatic cancer patients. Insights into the molecular characteristics of pancreatic cancer may provide valuable information, leading to its earlier detection and the development of targeted therapies. Material and Methods: We conducted a systematic review and a meta-analysis of studies that reported cfDNA in pancreatic ductal adenocarcinoma (PDAC). The studies were considered eligible if they included patients with PDAC, if they had blood tests for cfDNA/ctDNA, and if they analyzed the prognostic value of cfDNA/ctDNA for patients’ survival. The studies published before 22 October 2020 were identified through the PubMED, EMBASE, Web of Science and Cochrane Library databases. The assessed outcomes were the overall (OS) and progression-free survival (PFS), expressed as the log hazard ratio (HR) and standard error (SE). The summary of the HR effect size was estimated by pooling the individual trial results using the Review Manager, version 5.3, Cochrane Collaboration. The heterogeneity was assessed using the Cochran Q test and I2 statistic. Results: In total, 48 studies were included in the qualitative review, while 44 were assessed in the quantitative synthesis, with the total number of patients included being 3524. Overall negative impacts of cfDNA and KRAS mutations on OS and PFS in PDAC (HR = 2.42, 95% CI: 1.95–2.99 and HR = 2.46, 95% CI: 2.01–3.00, respectively) were found. The subgroup analysis of the locally advanced and metastatic disease presented similar results (HR = 2.51, 95% CI: 1.90–3.31). In the studies assessing the pre-treatment presence of KRAS, there was a moderate to high degree of heterogeneity (I2 = 87% and I2 = 48%, for OS and PFS, respectively), which was remarkably decreased in the analysis of the studies measuring post-treatment KRAS (I2 = 24% and I2 = 0%, for OS and PFS, respectively). The patients who were KRAS positive before but KRAS negative after treatment had a better prognosis than the persistently KRAS-positive patients (HR = 5.30, 95% CI: 1.02–27.63). Conclusion: The assessment of KRAS mutation by liquid biopsy can be considered as an additional tool for the estimation of the disease course and outcome in PDAC patients.

scholarly journals The prevalence of KRAS mutation in colorectal cancer patients in Iranian population: A systematic review and meta-analysis study

2017 ◽  
Vol 4 (10) ◽  
pp. 1693 ◽  
Author(s):  
Mehrdad Payandeh ◽  
Nasrin Amirifard ◽  
Masoud Sadeghi ◽  
Babak Shazad ◽  
Negin Farshchian ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Peer Review ◽  
Kras Mutation ◽  
Meta Analysis ◽  
Scientific Information ◽  
Geographical Area ◽  
Kras Mutations ◽  
Analysis Study ◽  
Peer Reviewers ◽  
Colorectal Cancer Patients

Colorectal cancer (CRC) is one of the most common cancers in the World that KRAS mutations are considered as a key step in the progression of CRC. This meta-analysis study aimed to evaluate the prevalence of KRAS mutations in CRC patients in Iran. Six online databases including PubMed, Science direct, Scopus, Web of science, Cochran Library, and Scientific Information Database (SID) were searched systematically up to January 2017. A random-effects meta-analysis was used to calculate the estimation of the prevalence of KRAS mutations in CRC patients by the event rate (ER) with 95% confidence interval (95%CI). Out of 82 articles identified from the search, eleven studies included and analyzed for meta-analysis study. The studies included 1814 CRC patients that mean age of the patients was 57.5 years. The pooled ER of the studies for estimation of the prevalence of KRAS mutation in CRC patients was 32.8% (95%CI=28.7-37.3%). The pooled ER of the studies for the prevalence of codon 12 mutation was 72.5% (95%CI=59.8-82.3%) and for codon 13 mutation was 20% (95%CI=14.6-26.7%). The results showed that the prevalence of KRAS mutation in Iran was different with more studies that therefore the geographical area and race can impact on the prevalence of KRAS mutation in CRC patients. Also, codon 12 had the most prevalence among mutant codons, followed by codon 13 that Gly to Asp and Gly to Val were the most mutations in codon 12.   Peer Review Details Peer review method: Single-Blind (Peer-reviewers: 02) Peer-review policy Plagiarism software screening?: Yes Date of Original Submission: 07 September 2017 Date accepted: 02 October 2017 Peer reviewers approved by: Dr. Lili Hami Editor who approved publication: Dr. Phuc Van Pham  

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