Pleural fluid analysis of lung cancer vs benign inflammatory disease patients

Kremer, Ran; Best, Lael‐Anson; Savulescu, Dana; Gavish, Moshe; Nagler, Rafael M.

doi:10.1038/sj.bjc.6605607

Cited by 17 publications

(16 citation statements)

References 38 publications

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“…Of the 80 selected studies, 18 were prospective, and the rest were retrospective. Seventy‐one studies were designed as a cohort, and nine were case‐control studies . Thirty‐three studies explicitly mentioned that the subjects were recruited consecutively …”

Section: Resultsmentioning

confidence: 99%

Are we ready to develop a tiered scheme for the effusion cytology? A comprehensive review and analysis of the literature

Farahani

Baloch

2019

Diagnostic Cytopathology

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Background: Cytology is widely utilized in the initial evaluation of fluid accumulation in the body cavities. The aim of this study was to determine the accuracy of cytology in distinguishing between benign and malignant (MAL) effusions. Methods:A comprehensive and systematic review of the literature was conducted to evaluate the accuracy of serous effusion cytology (SEC) against tissue biopsy/resection histology, imaging, or clinical follow-up as the reference test. Risk of publication bias and level of heterogeneity in the included studies was assessed. Meta-regression was performed to assess the effect of various variables on the accuracy of SEC. Results: Eighty studies met the inclusion criteria for meta-analysis comprising of 34 941 samples; of which 52 (0.2%), 22 202 (72.7%), 194 (0.6%), 711 (2.3%), and 6507 (21.3%) could be reclassified as nondiagnostic (ND), negative for malignancy (NFM), atypical (atypia of uncertain significance-AUS), suspicious for malignancy (SFM), and malignant (MAL), respectively. On follow-up, the mean risk of malignancy for ND, NFM, AUS, SFM, MAL was 17.4%, 20.7%, 65.9%, 81.8%, and 98.9%, respectively. A total of 73 studies were included in estimating the diagnostic accuracy of SEC. The bivariate mixed-effect model estimated the SEC sensitivity, specificity, diagnostic odds ratio, positive likelihood ratio, and negative likelihood ratio as 73.1%, 99.9%, 7850.6%, 2112.2%, and 0.27%, respectively. Conclusion: Serous effusion cytology shows high specificity and moderate sensitivity in the evaluation of serous effusions. A tiered classification scheme can improve the consistency of terminology for reporting SEC results, thus improving communication between the pathologists and clinical team, and quality of patient care. K E Y W O R D S analysis, classification scheme, comprehensive review, risk of malignancy, serous effusion cytology 1 | INTRODUCTION Serous effusion cytology (SEC) has been widely utilized in the initial evaluation of the etiology of fluid accumulation in the body cavities. Serous fluid can form in body cavities due to various inflammatory, infectious, and benign or malignant neoplasms. Malignancy is the underlying cause of serous effusion in 10% to 61% cases. 1,2 A majority of malignant effusions are caused by metastasis from adenocarcinoma of lung, breast, gastrointestinal, and female genital tract. 2,3 Malignant mesothelioma caninitially present as a serous effusion in up to 10% to 53% cases. 4-8

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Section: Resultsmentioning

confidence: 99%

Are we ready to develop a tiered scheme for the effusion cytology? A comprehensive review and analysis of the literature

Farahani

Baloch

2019

Diagnostic Cytopathology

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“…EGFR, ALK mutations). The limited tumour tissue and cell availability, the low and variable sensitivity of cytology (ranging from 43–91%) and the significant false-negative rate in the event of insufficient cell numbers from PE provided the impetus to investigate novel, complementary diagnostic markers 4 10 24 25 26 . The utilisation of cell-free DNA from blood samples as a surrogate for tumour biopsy to determine EGFR mutation status represents one such promising alternative that is currently evaluated clinically to assist the diagnosis of NSCLC 15 16 .…”

Section: Discussionmentioning

confidence: 99%

Lipidomic Profiling of Lung Pleural Effusion Identifies Unique Metabotype for EGFR Mutants in Non-Small Cell Lung Cancer

Yip

Basri

et al. 2016

Sci Rep

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Cytology and histology forms the cornerstone for the diagnosis of non-small cell lung cancer (NSCLC) but obtaining sufficient tumour cells or tissue biopsies for these tests remains a challenge. We investigate the lipidome of lung pleural effusion (PE) for unique metabolic signatures to discriminate benign versus malignant PE and EGFR versus non-EGFR malignant subgroups to identify novel diagnostic markers that is independent of tumour cell availability. Using liquid chromatography mass spectrometry, we profiled the lipidomes of the PE of 30 benign and 41 malignant cases with or without EGFR mutation. Unsupervised principal component analysis revealed distinctive differences between the lipidomes of benign and malignant PE as well as between EGFR mutants and non-EGFR mutants. Docosapentaenoic acid and Docosahexaenoic acid gave superior sensitivity and specificity for detecting NSCLC when used singly. Additionally, several 20- and 22- carbon polyunsaturated fatty acids and phospholipid species were significantly elevated in the EGFR mutants compared to non-EGFR mutants. A 7-lipid panel showed great promise in the stratification of EGFR from non-EGFR malignant PE. Our data revealed novel lipid candidate markers in the non-cellular fraction of PE that holds potential to aid the diagnosis of benign, EGFR mutation positive and negative NSCLC.

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“…However, gelatinases have been found to be significantly and specifically elevated in a number of malignant effusions including pericardial effusions. [17], [42] As a result, the superiority of Gel-NPs is probably owing to the gelatinase-responsive strategy.…”

Section: Discussionmentioning

confidence: 99%

Intelligently Targeted Drug Delivery and Enhanced Antitumor Effect by Gelatinase-Responsive Nanoparticles

Liu

et al. 2013

PLoS ONE

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AimsThe matrix metalloproteinase (MMP) 2/9, also known as collagenases IV and gelatinases A/B, play a key role in cancer invasion and metastasis. However, the clinical trials of the MMP inhibitors (MMPIs) ended up with disappointing results. In this paper, we synthesized a gelatinase-responsive copolymer (mPEG-PCL) by inserting a gelatinase cleavable peptide (PVGLIG) between mPEG and PCL blocks of mPEG-PCL for anticancer drug delivery to make use of MMP2/9 as an intelligent target for drug delivery.Materials and MethodsmPEG-pep-PCL copolymer was synthesized via ring-opening copolymerization and double-amidation. To evaluate whether Nanoparticles (NPs) prepared from this copolymer are superior to NPs prepared from mPEG-PCL, NPs prepared from mPEG-PCL copolymer were used as positive control. Docetaxel-loading NPs using mPEG-pep-PCL and mPEG-PCL were prepared by nano-precipitation method, mentioned as Gel-NPs and Con-NPs, respectively. The morphologic changes of the NPs after treatment with gelatinases were observed macroscopically by spectrophotometer and microscopically by transmission electron microscopy (TEM) and atomic force microscopy (AFM). The cellular uptake amount and cytotoxicity of Gel-NPs and Con-NPs, respectively, in cell lines with different levels of gelatinase expression were studied. Moreover, the cytotoxicity study on the primary cancer cells isolated from pericardial fluids from a patient with late-stage lung cancer was conducted.ResultsThe Gel-NPs aggregated in response to gelatinases, which was confirmed macroscopically and microscopically. The cellular uptake amount of Gel-NPs was correlated with the level of gelatinases. The in vitro antitumor effect of Gel-NPs was also correlated with the level of gelatinases and was superior to Taxotere (commercially available docetaxel) as well as the Con-NPs. The cytotoxicity study on the primary lung cancer cells also confirmed the effectiveness of Gel-NPs.ConclusionThe results in this study preliminarily demonstrated the effectiveness of gelatinase-responsive targeting strategy and the prospect of this intelligent nano-drug delivery system though further studies are needed.

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Pleural fluid analysis of lung cancer vs benign inflammatory disease patients

Cited by 17 publications

References 38 publications

Are we ready to develop a tiered scheme for the effusion cytology? A comprehensive review and analysis of the literature

Are we ready to develop a tiered scheme for the effusion cytology? A comprehensive review and analysis of the literature

Lipidomic Profiling of Lung Pleural Effusion Identifies Unique Metabotype for EGFR Mutants in Non-Small Cell Lung Cancer

Intelligently Targeted Drug Delivery and Enhanced Antitumor Effect by Gelatinase-Responsive Nanoparticles

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