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The value of computed tomography in discriminating malignant from non-malignant causes of unresolved unilateral pleural effusions: a systematic review.

ABSTRACT: The scientific background in expert-opinion papers for recommending Computed Tomography (CT) in unilateral pleural exudates is based on studies including patients with other findings than unilateral pleural effusions or selected patients undergoing thoracoscopy. Therefore, we performed a systematic review investigating the sensitivity of CT for predicting malignancy in patients with unilateral, non-transudative, pleural effusions. A search strategy was developed with the assistance of a medical information specialist at our university library. We searched PubMed/MEDLINE, EMBASE and Cochrane Library, ClinicalTrials.gov and articles citing the included studies. No date restrictions were applied (the first included paper was published in 2001 (1)), and only literature in English was included. We used the Quality Assessment of Diagnostic Accuracy Studies 2 for bias assessment. We registered the protocol at PROSPERO (CRD42018094830). Five studies were included, two prospective and three retrospective, all performed in Western Europe. No study reported diagnostic values for patients with unilateral, non-transudative pleural effusions only; one study did for unilateral pleural effusions. In the remaining studies, most patients had unilateral effusions and non-transudative effusions. Patients were primarily males and >70 years. All but one study found a high incidence of malignancy, dominated by malignant pleural mesothelioma. All studies were limited by risk of bias and applicability, predominantly regarding study population, pretests and index test. The current evidence supporting the sensitivity of CT for predicting malignancy in unilateral pleural effusions (both non-transudative and all types of effusion) is very low and did not allow meta-analysis. Standardization of patient population and CT protocol may facilitate conclusions of futures studies.

SUBMITTER: Reuter S

PROVIDER: S-EPMC8026111 | biostudies-literature |

REPOSITORIES: biostudies-literature

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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: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.

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The value of computed tomography in discriminating malignant from non-malignant causes of unresolved unilateral pleural effusions: a systematic review.

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