Pleural effusion biomarkers and computed tomography findings in diagnosing malignant pleural mesothelioma: A retrospective study in a single center

Our plain-English summary of Pleural effusion biomarkers and computed tomography findings in diagnosing malignant pleural mesothelioma: A retrospective study in a single center, by T. Otoshi, Y. Kataoka, S. Ikegaki, et al (PloS One, 2017).

The study

• Authors: T. Otoshi, Y. Kataoka, S. Ikegaki, E. Saito, H. Matsumoto, S. Kaku, M. Shimada, M. Hirabayashi
• Journal: PloS One
• Published: 2017;12(10):e0185850
• Cited by: 15 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

In this study, we aimed to examine the clinical value of the pleural effusion (PE) biomarkers, soluble mesothelin-related peptide (SMRP), cytokeratin 19 fragment (CYFRA 21-1) and carcinoembryonic antigen (CEA), and the utility of combining chest computed tomography (CT) findings with these biomarkers, in diagnosing malignant pleural mesothelioma (MPM). We conducted a retrospective cohort study in a single center. Consecutive patients with undiagnosed pleural effusions who underwent PE analysis between September 2014 and August 2016 were reviewed. This study included 240 patients (32 with MPM and 208 non-MPM). SMRP and the CYFRA 21-1/CEA ratio had a sensitivity and specificity for diagnosing MPM of 56.3% and 86.5%, and 87.5% and 74.0%, respectively. Using receiver operating characteristics (ROC) curve analysis of the ability of these markers to distinguish MPM from all other PE causes, the area under the ROC curve (AUC) for SMRP and the CYFRA 21-1/CEA ratio was 0.804 and 0.874, respectively. The sensitivity and specificity of SMRP combined with the CYFRA 21-1/CEA ratio were 93.8% and 64.9%, respectively. The sensitivity of the combination of SMRP, the CYFRA 21-1/CEA ratio, and the presence of Leung's criteria (a chest CT finding that is suggestive of malignant pleural disease) was 93.8%. In conclusion, the combined PE biomarkers had a high sensitivity for diagnosing MPM, although the addition of chest CT findings did not improve the sensitivity of SMRP combined with the CYFRA 21-1/CEA ratio. Combination of these biomarkers helped to rule out MPM effectively among patients at high risk of suffering MPM and would be valuable especially for old frail patients who have difficulty in undergoing invasive procedures such as thoracoscopy.

In plain English

This retrospective study at one hospital in Amagasaki, Japan, near a closed asbestos cement pipe plant, tested whether pleural fluid markers and CT scans help identify malignant pleural mesothelioma (MPM). It reviewed 240 patients with undiagnosed pleural effusions (fluid around the lungs) tested from September 2014 to August 2016: 32 had MPM and 208 were classified as non-MPM, including 47 still undiagnosed 12 months after testing. Patients' asbestos exposure was not reported. At a cut-off of 20 nmol/L, SMRP detected 56.3% of MPM patients (95% CI 50.0 to 73.6%) and was negative in 86.5% of non-MPM patients (95% CI 81.1 to 90.9%). The CYFRA 21-1 to CEA ratio (cut-off 19.1) detected 87.5% (95% CI 71.0 to 96.5%) and was negative in 74.0% (95% CI 67.5 to 79.9%). With missing values filled in, a positive result on either test detected 30 of 32 MPM patients (93.8%, 95% CI 79.2 to 99.2%) and was negative in 64.9% of non-MPM patients (95% CI 58.0 to 71.4%). Adding CT findings did not raise this. The authors concluded that low levels of both markers could strongly exclude MPM.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Retrospective single-center diagnostic accuracy study of hospital records
• Who was studied: 240 consecutive inpatients and outpatients with undiagnosed pleural effusions who had pleural fluid analysis at the Department of Respiratory Medicine of one hospital in Amagasaki, Japan, between September 2014 and August 2016. 32 had malignant pleural mesothelioma and 208 were classified as non-MPM. The non-MPM group included 47 patients classified as undiagnosed because none of the study's diagnostic criteria were met within 12 months after pleural fluid examination. Of an initial 272 patients, 32 were excluded.
• Exposure: This is not an exposure study, and the article does not report individual patients' asbestos exposure. It evaluated diagnostic tests: pleural fluid SMRP (cut-off 20 nmol/L), the pleural fluid CYFRA 21-1/CEA ratio (cut-off 19.1), and chest CT features of pleural thickening (Leung's criteria). The authors state that the hospital, both before and after its 2015 move, lies within 2000 m of a closed asbestos cement pipe plant.
• Main results:
  • SMRP at a cut-off of 20 nmol/L, all 240 patients: sensitivity 56.3% (95% CI 50.0 to 73.6%) and specificity 86.5% (95% CI 81.1 to 90.9%) for diagnosing MPM.
  • CYFRA 21-1/CEA ratio at a cut-off of 19.1, all 240 patients: sensitivity 87.5% (95% CI 71.0 to 96.5%) and specificity 74.0% (95% CI 67.5 to 79.9%).
  • SMRP combined with the CYFRA 21-1/CEA ratio (positive if either was positive), all 240 patients with missing values imputed: sensitivity 93.8% (95% CI 79.2 to 99.2%) and specificity 64.9% (95% CI 58.0 to 71.4%). 30 of 32 MPM patients tested positive.
  • Area under the ROC curve for telling MPM apart from all other causes: SMRP 0.804 (95% CI 0.690 to 0.918) and CYFRA 21-1/CEA ratio 0.874 (95% CI 0.780 to 0.948). The difference between the two was not statistically significant (p = 0.13).
  • Adding any chest CT finding (Leung's criteria or any of its four individual features) to the combined biomarkers left sensitivity unchanged at 93.8% (95% CI 79.2 to 99.2).
  • Each of the four CT features of pleural thickening was significantly more common in MPM patients than in non-MPM patients: circumferential thickening 22% vs 7%, nodularity 69% vs 20%, thickness greater than 1 cm 50% vs 14%, and mediastinal pleural involvement 66% vs 30%.
  • In a subgroup analysis distinguishing MPM from other malignant tumors (lung cancer and other malignancy), the combined biomarkers had sensitivity 93.8% (95% CI 79.2 to 99.2) and specificity 72.1% (95% CI 59.2 to 82.9).
  • In a sensitivity analysis limited to patients with complete data, the combined biomarkers had a sensitivity of 96.4% (95% CI 81.7 to 99.9%).
• The authors' conclusion: The authors concluded that low levels of the pleural fluid markers SMRP and the CYFRA 21-1/CEA ratio could strongly exclude MPM. They considered the combination useful for ruling out MPM in patients at high risk, especially frail older patients who have difficulty undergoing invasive procedures such as thoracoscopy.
• Limitations the authors state:
  • Some patients who had pleural fluid analysis were excluded (32 of 272).
  • The reference standard could have introduced bias because it was interpreted with knowledge of the chest CT findings.
  • Because the study was retrospective, some pleural fluid SMRP and CYFRA 21-1/CEA values were missing, and multiple imputation was used to fill them in statistically.
  • Seven MPM patients were diagnosed only by cytology, so their MPM subtypes were not known.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma, Pleural plaques and thickening.

Medical terms in this study, explained in our Lexicon: Pleural Effusion, Biomarker, Pleural Mesothelioma, Mesothelin, Soluble Mesothelin-Related Peptides (SMRP), Carcinoembryonic Antigen (CEA), Cohort Study, Thoracoscopy.

Related studies

• Evaluation of pleural CYFRA 21-1 and carcinoembryonic antigen in the diagnosis of malignant pleural effusions — G. Salama, M. Miédougé, et al. (1998)
• A retrospective study on radiological findings of diffuse pleural thickening with benign asbestos pleural effusion in Japanese cases — T. Kishimoto, K. Kato, et al. (2022)
• Agreement between chest radiography and high-resolution computed tomography in diagnosing dust-related interstitial lung fibrosis — R.R. Tiwari (2015)
• Computed tomography findings in 66 patients with malignant pleural mesothelioma due to environmental exposure to asbestos — F. Okten, D. Köksal, et al. (2006)
• Fatal pleural mesothelioma in Japan (2003-2008): evaluation of computed tomography findings — K. Kato, K. Gemba, et al. (2016)
• Computed tomography findings of peritoneal tumour in the absence of primary lesions: preliminary study — T. Tanaka, M. Tomihari, et al. (2026)

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