Hyaluronic acid in the pleural fluid of patients with malignant pleural mesothelioma

Our plain-English summary of Hyaluronic acid in the pleural fluid of patients with malignant pleural mesothelioma, by N. Fujimoto, K. Gemba, M. Asano, et al (Respiratory Investigation, 2013).

The study

• Authors: N. Fujimoto, K. Gemba, M. Asano, Y. Fuchimoto, S. Wada, K. Ono, S. Ozaki, T. Kishimoto
• Journal: Respiratory Investigation
• Published: 2013;51(2):92-7
• Cited by: 34 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background: We retrospectively analyzed hyaluronic acid (HA) concentrations in pleural fluid and evaluated its utility for the differential diagnosis of malignant pleural mesothelioma (MPM).

Methods: Pleural fluid HA concentrations were measured in 334 patients, including 50, 48, 85, 18, 86, 6, and 41 patients with MPM, benign asbestos pleurisy (BAP), lung cancer (LC), other malignant conditions (OMCs), infectious pleuritis (IP), collagen disease (CD), and other conditions, respectively.

Results: The median (range) HA concentrations in pleural fluid were 78,700 (7920-2,630,000)ng/ml in the MPM group, 35,950 (900-152,000)ng/ml in the BAP group, 19,500 (2270-120,000)ng/ml in the LC group, 14,200 (900-101,000)ng/ml in the OMC group, 23,000 (900-230,000)ng/ml in the IP group, 24,600 (9550-80,800)ng/ml in the CD group, and 8140 (900-67,800)ng/ml in the other diseases group. HA levels were significantly higher in the MPM group than in the other groups. Receiver operating characteristic (ROC) analysis revealed an area under the ROC curve value of 0.832 (95% confidence interval, 0.765-0.898) for the differential diagnosis of MPM. With a cutoff value of 100,000ng/ml, the sensitivity and specificity were 44.0 and 96.5%, respectively. In the MPM group, HA values were significantly higher for the epithelioid subtype than for the sarcomatous subtype (p=0.007), and higher in earlier stages (I and II) than in advanced stages (III and IV) (p=0.007).

Conclusions: A diagnosis of MPM should be strongly considered in patients with pleural fluid HA concentrations exceeding 100,000ng/ml.

Copyright © 2013 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.

In plain English

This retrospective study from Okayama Rosai Hospital in Japan looked at hyaluronic acid (HA) levels recorded in the pleural fluid of 334 patients with pleural effusion (fluid around the lungs) seen between December 2005 and August 2010. The aim was to test whether HA helps tell malignant pleural mesothelioma (MPM) apart from other conditions. The patients included 50 with MPM, 48 with benign asbestos pleurisy, 85 with lung cancer and 86 with infectious pleuritis, along with smaller groups. Median HA was 78,700 ng/ml in the MPM group, significantly higher than in the other groups. Using a cutoff of 100,000 ng/ml, sensitivity was 44.0% (the share of MPM patients above the cutoff) and specificity was 96.5% (the share of other patients below it). Of the 32 patients above that level, 22 had MPM. Among MPM patients, HA was higher in the epithelioid subtype than in the sarcomatous subtype, and higher in stages I and II than in stages III and IV. The authors concluded that MPM should be highly suspected above 100,000 ng/ml. They also concluded that telling MPM apart from benign asbestos pleurisy required thoracoscopic examination.

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 analysis of hospital medical records (diagnostic marker study)
• Who was studied: 334 patients with pleural effusion at Okayama Rosai Hospital, Japan, December 2005 to August 2010: 50 with MPM, 48 with benign asbestos pleurisy, 85 with lung cancer, 18 with other malignant diseases, 86 with infectious pleuritis, 6 with collagen disease and 41 with other diseases
• Exposure: This is not an exposure study. The measurement studied was hyaluronic acid in pleural fluid, measured by latex agglutination turbidimetric immunoassay. Benign asbestos pleurisy was diagnosed only in patients with previous asbestos exposure. No fiber types, jobs or doses are given.
• Main results:
  • Median (range) pleural fluid HA was 78,700 (7920 to 2,630,000) ng/ml in the MPM group and 35,950 (900 to 152,000) ng/ml in the benign asbestos pleurisy group. HA in the MPM group was significantly higher than in the other groups.
  • For distinguishing MPM from the other groups, the area under the ROC curve was 0.832 (95% confidence interval 0.765 to 0.898).
  • At a cutoff of 100,000 ng/ml, sensitivity was 44.0% and specificity was 96.5%. At 150,000 ng/ml, sensitivity was 32.0% and specificity was 99.3%.
  • 32 of the 334 patients (9.6%) had HA above 100,000 ng/ml. Of these, 22 had MPM. The results text describes the other 10 as 4 with benign asbestos pleurisy, 4 with infectious pleuritis, 1 with lung cancer and 1 with pharyngeal cancer.
  • About 10% of patients with benign asbestos pleurisy had HA above 100,000 ng/ml.
  • Among the 50 MPM patients (34 epithelioid, 8 biphasic, 6 sarcomatous, 2 desmoplastic), HA was significantly higher in the epithelioid subtype than in the sarcomatous subtype (p = 0.007).
  • Among MPM patients, HA was higher in stages I and II than in stages III and IV (p = 0.007). Among epithelioid cases alone, HA was lower in more advanced stages, but this difference was not statistically significant.
  • The authors found no difference in survival between MPM patients with HA above and below 100,000 ng/ml (data not shown).
• The authors' conclusion: The authors concluded that patients with pleural fluid HA above 100,000 ng/ml should be highly suspected of having MPM. They also concluded that differentiating MPM from benign asbestos pleurisy requires thoracoscopic exploration.
• Limitations the authors state:
  • Sensitivity (44.0% at 100,000 ng/ml) was lower than previously reported.
  • HA levels were lower in the sarcomatous subtype, so the authors stated that a more accurate marker is needed for detecting sarcomatous MPM.
  • Because HA was lower in advanced stages, the authors suggested the test might only be useful in early-stage MPM.

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: Hyaluronic Acid, Pleural Mesothelioma, Differential Diagnosis, Pleurisy, Lung Cancer, Collagen, confidence interval, Epithelioid.

Related studies

• Utility of hyaluronic acid in pleural fluid for differential diagnosis of pleural effusions: likelihood ratios for malignant mesothelioma — S. Atagi, M. Ogawara, et al. (1997)
• Pleural effusion hyaluronic acid as a prognostic marker in pleural malignant mesothelioma — J. Creaney, I.M. Dick, et al. (2013)
• Mesothelioma of the peritoneum; a case report in which the ascitic fluid contained hyaluronic acid — S. Dvoskin (1954)
• Serum mesothelin has a higher diagnostic utility than hyaluronic acid in malignant mesothelioma — B. Grigoriu, B. Chahine, et al. (2009)
• Histochemical demonstration of hyaluronic acid in pleural mesotheliomas — J.C. Wagner, D.E. Munday, et al. (1962)
• Clinical significance of the immunometric measurements of hyaluronic acid — E.H. Cooper, B.J. Rathbone (1990)

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