Evaluation of two strategies for the interpretation of tumour markers in pleural effusions

Trapé, Jaume; Sant, Francesc; Franquesa, Josefina; Montesinos, J.; Arnau, Anna; Sala, María; Bernadich, Òscar; Martín, Esperanza; Perich, Damià; Pérez, C.; López, Joan; Ros, S.; Esteve, Enrique; Pérez, Rafael; Aligué, Jordi; Gurt, Gabriel; Catot, Sílvia; Domènech, Montserrat; Bosch, Joan; Badal, Josep; Bonet, Mariona; Molina, Rafael; Ordeig, Josep

doi:10.1186/s12931-017-0582-1

Cited by 22 publications

(28 citation statements)

References 26 publications

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“…Moreover, our findings are in agreement with previous clinical studies (Feng et al 2017;Gu et al 2017;Holdenrieder et al 2017;Cedrés et al 2011;Trape et al 2017;Topolcan et al 2007;Antonangelo et al 2015;Sharma et al 2015), and achieved better performance in detecting malignant effusion showing a sensitivity of 98%, a specificity of 95%, and an AUC of 96%. Probably, the low performance of the other studies is due to the low number of MPEs with negative cytology and to the variety of primary tumor sites that they considered (Antonangelo et al 2015;Sharma et al 2015).…”

Section: Discussionsupporting

confidence: 93%

A machine learning evolutionary algorithm-based formula to assess tumor markers and predict lung cancer in cytologically negative pleural effusions

et al. 2019

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Malignant pleural effusion is diagnostically challenging in presence of negative cytology. The assessment of tumor markers in serum has become a standard tool in cancer diagnosis, while pleural fluid sampling has not met universal consensus. The evaluation of a panel of markers both in serum and pleural fluid may be crucial to improve the diagnostic accuracy. Using a machine learning-based approach, we provide a mathematical formula capable to express the complex relation existing among the expressed markers in serum and pleural effusion and the presence of lung cancer. The formula indicates CEA and CYFRA21-1 in pleural fluid as the best diagnostic markers, with 97% accuracy, 98% sensitivity, 95% specificity, 96% area under curve, 98% positive predictive value, and 92% MCC (Matthews correlation coefficient).

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Section: Discussionsupporting

confidence: 93%

A machine learning evolutionary algorithm-based formula to assess tumor markers and predict lung cancer in cytologically negative pleural effusions

et al. 2019

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“…This study assessed two strategies for evaluating tumor markers in ascites. Our results are in agreement with previous studies that have used the strategy of the F/S ratio (19)(20)(21), showing better sensitivity values (75.7%) compared to the strategy of a single measurement in fluid with a high cut-off point. For the whole group of patients analyzed, the specificity obtained was 95.2%.…”

Section: Discussionsupporting

confidence: 93%

“…The following tests were performed in fluid and/or serum in order to identify benign effusions: protein (biuret method, albumin (bromochresol purple), lactate dehydrogenase (LDH) (lactate to pyruvate), rheumatoid factor in LX- 20 ADA: Adenosine deaminase; CRP: C reactive protein; % PN: % polymorphonuclear cells; PPSC: papillary peritoneal serous carcinoma; CUP: cancer of unknown primary.…”

Section: Methodsmentioning

confidence: 99%

“…TM in serum were measured only in patients with higher TM values in the effusion fluid compared to the URL in the serum (5 mg/l for CEA; 30 ku/l for CA15-3; 6.9 ku/l for CA72-4, and 37 ku/l for CA19-9). The criteria used to indicate a possible false positive effusion (i.e., peritonitis, inflammation, or a tuberculous effusion) were %PN>90, CRP>50 mg/l or ADA >45 u/l (19,20). The use of biomarkers ADA, CRP and %PN identified two groups of effusions: i) group A, with effusions containing all biomarkers under the cutoff point, and ii) group B, with effusions containing at least one positive biomarker.…”

Section: Methodsmentioning

confidence: 99%

“…Similarly, subclassifying these effusions according to their ADA, CRP and % of polymorphonuclear cells (%PN) value, we obtained a sensitivity of 80% and a specificity of 100% in patients with negative ADA, CRP and %PN using the F/S ratio. In a recent study using this strategy we found similar sensitivities for CEA, CA15-3, CA19-9 and Cancer antigen 72-4 (CA72-4) in pleural effusion (20). This strategy is less accurate for tumor markers secreted by mesothelial cells, such as cancer antigen 125 (CA125) and cytokeratin 19 fragments (CYFRA 21-1) that are best interpreted with a single determination in fluid effusion (21,22).…”

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confidence: 88%

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Comparative Assessment of Two Strategies for Interpreting Tumor Markers in Ascitic Effusions

Trapé

Sant

Montesinos

et al. 2020

In Vivo

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Background/Aim: There are two strategies for the interpretation of tumor markers (TM) in fluid effusions: i) high cutoff and ii) fluid/serum ratio (F/S) and low cutoff. The objective of this study is to compare these two strategies and to determine whether diagnostic accuracy improves by the identification of possible false positives using Adenosine deaminase (ADA), C reactive protein (CRP) and % of polymorphonuclear cells (%PN). Patients and Methods: We studied 157 ascitic fluids, 74 of which were malignant. ADA, CRP and %PN were determined in ascitic fluid, and Carcinoembryonic antigen (CEA), Cancer antigen 72-4 (CA72-4), Cancer antigen CA19-9 and Cancer antigen 15-3 (CA15-3) in both fluid and serum. Results: The strategy of high cutoff showed 59.5% sensitivity at 100% specificity. The F/S strategy showed 75.7% sensitivity at 95.2% specificity. Subclassifying cases with ADA, CRP and %PN negative showed 67.5% sensitivity at 100% specificity for high cutoff and for the F/S strategy was 81.7% sensitivity at 98.7% specificity. Conclusion: The strategy of F/S with negative ADA, CRP and %PN allow the best interpretation for TM in the ascitic fluid. Ascites is the abnormal accumulation of fluid in the peritoneal cavity. It is mostly seen in patients with liver disease, pancreatic disease, tuberculous peritonitis, congestive heart failure, kidney disease, acquired immune deficiency syndrome and cancer (1). Cytology is the gold standard for confirming the presence of malignant cells in ascitic fluid, but its sensitivity only ranges between 50 and 70% (2). The main cause of this low sensitivity is the fact that a primary tumor may infiltrate the peritoneum but may not shed cells, with a negative result in the cytological analysis. In these cases, other invasive procedures, such as laparoscopy may be needed to confirm the presence of malignant cells. The potential of tumor markers (TM) for improving the diagnosis of malignant pleural and peritoneal effusions has been mentioned by several authors but there are major discrepancies between the reports regarding their specificity and sensitivity, and also in terms of the cutoff values used (3-5): for Carcinoembryonic antigen (CEA) the range is 2-50 ng/ml and for Cancer antigen 19-9 (CA19-9) it is 14.5-200 ku/l (6-10). Their sensitivity ranges between 24% and 77% and their specificity from 82% to 100% (6-10).

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Analysis of tumor markers in pleural effusion and serum to verify the correlations between serum tumor markers and tumor size, TNM stage of lung adenocarcinoma

2019

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Background The study of tumor markers (TM) in pleural effusion (PE) was not extensive. Methods TM in PE and serum were analyzed to determine whether TM was expressed in intrathoracic and extrathoracic tissues. To further verify the correlations between serum TM and tumor size, TNM stage of lung adenocarcinoma. Results Serum AFP was not correlated with tumor size, T stage, N stage, and M stage (P > .05). Serum CEA, serum CA125, serum CA15‐3 were positively correlated with tumor size, T stage, N stage, M stage (P < .05). Serum CA19‐9 was not significantly correlated with tumor size and T stage (P > .05), but was positively correlated with N stage and M stage (P < .05). The levels of PE CEA, PE CA125, PE CA15‐3 were higher than those of serum CEA, serum CA125, serum CA15‐3 (all P < .05). The level of PE AFP was lower than that of serum AFP (P < .05). The level of PE CA19‐9 was not significantly different from that of serum CA19‐9 (P > .05). The positive rates of PE CEA and PE CA125 were higher than those of serum CEA and serum CA125 (P < .05). The positive rates of PE AFP, PE CA15‐3, PE CA19‐9 were not significantly different from those of serum AFP, serum CA15‐3, serum CA19‐9 (P > .05).PE CEA, PE CA125, PE CA15‐3 were moderately positively correlated with serum CEA, serum CA125, serum CA15‐3, respectively (r = 0.597; r = 0.46; r = 0.583, all P < .05). However, PE AFP and PE CA19‐9 were very strongly positively correlated with serum AFP and serum CA19‐9, respectively (r = 0.888; r = 0.874, all P < .05). Conclusion The expression characteristics of TM in PE and serum supported the correlations between serum TM and tumor size, TNM stage of lung adenocarcinoma.

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Evaluation of two strategies for the interpretation of tumour markers in pleural effusions

Cited by 22 publications

References 26 publications

A machine learning evolutionary algorithm-based formula to assess tumor markers and predict lung cancer in cytologically negative pleural effusions

A machine learning evolutionary algorithm-based formula to assess tumor markers and predict lung cancer in cytologically negative pleural effusions

Comparative Assessment of Two Strategies for Interpreting Tumor Markers in Ascitic Effusions

Analysis of tumor markers in pleural effusion and serum to verify the correlations between serum tumor markers and tumor size, TNM stage of lung adenocarcinoma

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