Confocal Laser Endomicroscopy as a Guidance Tool for Pleural Biopsies in Malignant Pleural Mesothelioma

Our plain-English summary of Confocal Laser Endomicroscopy as a Guidance Tool for Pleural Biopsies in Malignant Pleural Mesothelioma, by L. Wijmans, P. Baas, T.E. Sieburgh, et al (Chest, 2019).

The study

• Authors: L. Wijmans, P. Baas, T.E. Sieburgh, D.M. de Bruin, P.M. Ghuijs, M.J. van de Vijver, P.I. Bonta, J.T. Annema
• Journal: Chest
• Published: 2019;156(4):754-763
• Cited by: 28 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background: Pleural biopsies in patients with suspected malignant pleural mesothelioma (MPM) are often inconclusive resulting in repeat diagnostic procedures. Confocal laser endomicroscopy (CLE) enables real-time imaging on a cellular level. We investigated pleural CLE imaging as a biopsy guidance technique to distinguish malignant from benign pleural disease.

Methods: Prospective, multicenter study in patients with (suspected) MPM based on PET-CT imaging who were scheduled for pleural biopsies. Patients received 2.5 mL fluorescein intravenously preceding the procedure. In vivo through-the-needle CLE imaging of the pleura and ex vivo CLE imaging of the biopsies were correlated with histology. CLE characteristics for various pleural entities were identified, and their interpretability was tested by CLE video scoring by multiple blinded raters.

Results: CLE imaging was successfully obtained in 19 of 20 diagnostic pleural biopsy procedures (thoracoscopy: n = 4, surgical excision: n = 3, CT scan: n = 3, ultrasound: n = 9, esophageal ultrasound guided: n = 1) in 15 patients. CLE videos (n = 89) and corresponding pleural biopsies (n = 105) were obtained. No study-related adverse events occurred. Tumor deposits of MPM were distinguished from areas with pleural fibrosis based on CLE imaging and recognized by raters (n = 3) (interobserver agreement, 0.56; 95% CI, 0.49-0.64).

Conclusions: CLE imaging was feasible and safe regardless of the biopsy method. Real-time visualization of pleural abnormalities in epithelial and sarcomatoid MPM could be distinguished from pleural fibrosis. Therefore, CLE has potential as a guidance biopsy tool to reduce the current substantial rate of repeat biopsy procedures by identification of areas with malignant cells in vivo (smart needle).

Trial Registry: ClinicalTrials.gov; No.: NCT02689050; URL: www.clinicaltrials.gov.

Copyright © 2019. Published by Elsevier Inc.

In plain English

This prospective multicenter feasibility study in Amsterdam (August 2017 to April 2018) tested whether confocal laser endomicroscopy (CLE), an imaging probe showing individual cells, could help guide pleural biopsies in suspected malignant pleural mesothelioma (MPM). The study did not examine asbestos exposure. Fifteen patients (13 men, 2 women; 11 finally diagnosed with MPM) received intravenous fluorescein dye and underwent 20 biopsy procedures. Imaging failed in one thoracoscopy because the dye had not reached the pleura. No study-related adverse events occurred. On CLE images, pleural fibrosis looked different from epithelial-type mesothelioma. Needle-based CLE produced 55 videos from 26 biopsy locations, 17 of them malignant. Three trained raters without pathology background detected malignancy in 14 of 17 (82%); the article calls these videos, but 17 is its count of malignant locations. During thoracoscopy, CLE identified 11 of 14 malignant locations and white-light viewing identified 9 of 14. Agreement between the raters was moderate (0.56; 95% CI, 0.49-0.64). The authors concluded that CLE has potential as a biopsy guidance tool, noting the small number of patients and overrepresentation of epithelial-type 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: Prospective multicenter feasibility study of an imaging technique (CLE) used during pleural biopsy. CLE images were compared against biopsy histology and scored by blinded raters.
• Who was studied: 15 patients (13 men and 2 women) with suspected or known malignant pleural mesothelioma who were scheduled for diagnostic pleural biopsies at Amsterdam University Medical Centers and The Netherlands Cancer Institute, Amsterdam, August 2017 to April 2018. They underwent 20 procedures. Final diagnoses were epithelial MPM in 9 patients, sarcomatoid MPM in 2, non-small cell lung cancer (adenocarcinoma) in 1, thymoma in 1 and nonspecific pleuritis in 2.
• Exposure: Asbestos exposure was not studied. The intervention studied was CLE imaging (needle-based and probe-based) during pleural biopsy procedures, after 2.5 mL of fluorescein solution was given intravenously.
• Main results:
  • Of the 15 patients, 11 had a final diagnosis of MPM.
  • In one thoracoscopy procedure, the first in the study, CLE imaging was not good enough to analyze because the fluorescein had not reached the pleura.
  • No study-related adverse events occurred.
  • Across procedures, 89 in vivo CLE measurements, 50 ex vivo CLE measurements and 105 pleural biopsies were obtained.
  • On CLE images, fibrotic pleura (a non-cellular bundle pattern) could be told apart from epithelial-type MPM (a cellular pattern with cells of varied shape and size).
  • In 14 needle-based CLE procedures, 55 videos were recorded from 26 biopsy locations (17 malignant, 9 benign).
  • For needle-based CLE, the blinded raters detected malignancy in 14 of 17 (82%). The article words this as a result for videos, but 17 is the number of malignant biopsy locations it reports, not the number of videos, so the unit of this figure is unclear.
  • During thoracoscopy (3 evaluable procedures, 14 malignant biopsy locations), the raters detected malignancy on CLE in 11 of 14 malignant areas. Conventional white light detected 9 of 14.
  • During thoracoscopy, white light and CLE combined detected 13 of 14 biopsy locations with malignancy.
  • On average, raters detected malignancy on CLE imaging after 32 seconds.
  • Agreement among the three raters for detecting malignancy across all CLE recordings was moderate: 0.56 (95% CI, 0.49-0.64).
• The authors' conclusion: The authors concluded that epithelial- and sarcomatoid-type MPM could be identified in real time and distinguished from pleural fibrosis on CLE imaging. They concluded that CLE has potential as a real-time biopsy guidance tool.
• Limitations the authors state:
  • The study included a small number of patients (15).
  • Epithelial-type MPM was overrepresented, which limits conclusions about other types of pleural disease.
  • The raters had CLE training but no background in pathology.
  • Where the raters disagreed, the histology was benign or sarcomatoid-type mesothelioma.
  • Rapid on-site cytologic evaluation (ROSE) was not available for comparison with CLE.
  • Whether the non-cellular bundle pattern is specific for pleural fibrosis remains to be proven in future studies.

Topics

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

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Biopsy, PET-CT, Pleura, Histology, Pleural Biopsy, Thoracoscopy, CT Scan.

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