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Diagnostic value of tumour markers in pleural effusions.

ABSTRACT: Introduction:We investigated whether tumour markers carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), cancer antigen 125 (CA-125), and cytokeratin 19 fragment (CYFRA 21-1) in pleural effusions and serum can be used to distinguish pleural effusion aetiology. Materials and methods:During the first thoracentesis, we measured pleural fluid and serum tumour marker concentrations and calculated the pleural fluid/serum ratio for patients diagnosed with pleural effusion, using electrochemiluminescence immunoassays. Receiver operating characteristic (ROC) analysis was carried out and the Hanley and McNeil method was used to test the significance of the difference between the areas under ROC curves (AUCs). In order to detect which tumour marker best discriminates between malignant and non-malignant pleural effusions and to establish the predictive value of those markers, discriminant function analysis (DFA) and logistic regression analysis were utilized. Results:Serum tumour markers CYFRA 21-1 and NSE as well as pleural NSE were good predictors of pleural effusion malignancy and their combined model was found statistically significant (Chi-square = 28.415, P < 0.001). Respective ROC analysis showed significant discrimination value of the combination of these three markers (AUC = 0.79). Conclusions:Serum markers showed superiority to pleural fluid markers in determining pleural fluid aetiology. Serum CYFRA 21-1 and NSE concentrations as well as pleural fluid NSE values had the highest clinical value in differentiating between malignant and non-malignant pleural effusions. The combination of these three markers produced a significant model to resolve pleural effusion aetiology.

SUBMITTER: Volaric D

PROVIDER: S-EPMC5806614 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Diagnostic value of tumour markers in pleural effusions.

Volarić Darian D Flego Veljko V Žauhar Gordana G Bulat-Kardum Ljiljana L

Biochemia medica 20180110 1

<h4>Introduction</h4>We investigated whether tumour markers carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), cancer antigen 125 (CA-125), and cytokeratin 19 fragment (CYFRA 21-1) in pleural effusions and serum can be used to distinguish pleural effusion aetiology.<h4>Materials and methods</h4>During the first thoracentesis, we measured pleural fluid and serum tumour marker concentrations and calculated the pleural fluid/serum ratio for patients diagnosed with pleural effusion, usin ...[more]

PMID: 29472801

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Project description:Pleural effusions (PE) are a common clinical problem. The discrimination between benign (BPE), malignant (MPE) and paramalignant (PPE) pleural effusions is highly important to ensure appropriate patient treatment. Today, cytology is the gold standard for diagnosing malignant pleural effusions. However, its sensitivity is limited due to the sometimes low abundance of tumor cells and the challenging assessment of cell morphology in cytological samples. This study aimed to develop and validate a diagnostic test, which allows for the highly specific detection of malignant cells in pleural effusions based on the DNA methylation biomarkers SHOX2 and SEPT9. A quantitative real-time PCR assay was developed which enabled the accurate and sensitive detection of SHOX2 and SEPT9 in PEs. Cytological and DNA methylation analyses were conducted in a case control study comprised of PEs from 114 patients (58 cases, 56 controls). Cytological analysis as well as SHOX2 and SEPT9 methylation resulted in 100% specificity. 21% of the cases were cytologically positive and 26% were SHOX2 or SEPT9 methylation positive. The combined analysis of cytology and DNA methylation resulted in an increase of 71% positively classified PEs from cancer patients as compared to cytological analysis alone. The absolute sensitivity of cytology and DNA methylation was not determinable due to the lack of an appropriate gold standard diagnostic for distinguishing between MPEs and PPEs. Therefore, it was unclear which PEs from cancer patients were malignant (containing tumor cells) and which PEs were paramalignant and resulted from benign conditions in cancer patients, respectively. Furthermore, DNA methylation analysis in PEs allowed the prognosis of the overall survival in cancer patients (Kaplan-Meier analysis, log rank test, p=0.02 (SHOX2), p=0.02 (SEPT9)). The developed test may be used as a diagnostic and prognostic adjunct to existing clinical and cytopathological investigations in patients with PEs of unclear etiology.

Project description:IntroductionPleural effusions frequently signal disseminated cancer. Diagnostic markers of pleural malignancy at presentation that would assess cancer risk and would streamline diagnostic decisions remain unidentified.MethodsA consecutive cohort of 323 patients with pleural effusion (PE) from different etiologies were recruited between 2013 and 2017 and was retrospectively analyzed. Data included history, chest X-ray, and blood/pleural fluid cell counts and biochemistry. Group comparison, receiver-operator characteristics, unsupervised hierarchical clustering, binary logistic regression, and random forests were used to develop the malignant pleural effusion detection (MAPED) score. MAPED was validated in an independent retrospective UK cohort (n = 238).ResultsFive variables showed significant diagnostic power and were incorporated into the 5-point MAPED score. Age > 55 years, effusion size > 50% of the most affected lung field, pleural neutrophil count 〈 2,500/mm3, effusion protein 〉 3.5 g/dL, and effusion lactate dehydrogenase > 250 U/L, each scoring one point, predicted underlying cancer with the area under curve(AUC) = 0.819 (P < 10-15) in the derivation cohort. The integrated discrimination improvement of MAPED scores showed an increase compared to cytology (p <0.001). Decision curve analysis indicated that the MAPED score generated net clinical benefit. In the validation dataset, the AUC of MAPED scores was 0.723 ( P = 3 × 10-9) for the MAPED score. Interestingly, MAPED correctly identified 33/42(79%) of cytology-negative patients that indeed had cancer.ConclusionsThe MAPED score identifies malignant pleural effusions with satisfactory accuracy and can be used complementary to cytology to streamline diagnostic procedures.Condensed abstractDiagnostic markers for malignant pleural effusions remain uncertain. The MAPED score identifies malignant pleural effusions and complements cytology and confers no additional risk to the patient or cost to the healthcare system.

Project description:Background and objectivePleural effusions (PEs) are commonly seen in various pathologies and have a significant impact on patient health and quality of life. Unlike for malignant PEs, non-malignant PEs (NMPEs) do not have well-established guidelines. Much of the evidence base in this field is from a handful of randomised controlled trials (RCTs) and the majority are from retrospective cohort analyses and cases series. Cardiac related PEs fall within the entity of NMPEs and the aim of this narrative review is to gather the existing evidence in the field of congestive heart failure (CHF), pericarditis and post-cardiac injury syndrome (PCIS). This narrative review investigates the pathophysiology, diagnostic criteria and treatment options for the various cause of cardiac related PEs.MethodsThis narrative review is based on a comprehensive literature search analysing RCTs, prospective and retrospective cohort analyses and published case series.Key content and findingsCHF related PEs have a substantial mortality rate and carry a worse prognosis if the PEs are bilateral and transudative in nature. Light's criteria have often shown to misclassify transudative effusions in CHF (pseudo-exudates) and hence measuring serum-pleural albumin gradient is an invaluable tool to accurately identify transudates. Elevated serum and pleural N-terminal pro-B type natriuretic peptide (NT-proBNP) has shown increasing evidence of correctly identifying PEs secondary to CHF. However, they should be considered with the pre-test probability of CHF. Therapeutic thoracentesis and indwelling pleural catheter (IPC) placement may be necessary if medical management has failed. PEs can also occur secondary to pericarditis and are often small, bilateral and exudative. PCIS also results in PEs and are commonly seen in post-coronary artery bypass graft (CABG) surgery. Both entities need management of the underlying cause first, but in cases where PEs are refractory, individualised pleural interventions may be necessary.ConclusionsThis comprehensive narrative review provides valuable insights into the aetiology, diagnosis and management of PEs secondary to CHF, pericarditis and PCIS. The aim is to enhance the clinicians' knowledge of this complex and controversial topic to improve patient care of cardiac-related PEs. Ongoing trials in this field will be able to provide valuable insights.

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Diagnostic value of tumour markers in pleural effusions.

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Diagnostic value of tumour markers in pleural effusions.

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