Pleural Diseases in the Molecular Era – Time for More Answers: Introduction

rence of pleural effusion in this patient population. Also, a major unanswered question is whether the occurrence of pleural effusion has any prognostic value. Thus, an issue of the present thematic review series is focused on the advances in the understanding of the mechanisms of pleural effusion in patients with orphan diseases. Prof. Demosthenes Bouros et al. will cover this issue under the title: ‘Mechanisms of Pleural Involvement in Orphan Diseases’. Lung cancer remains the most common fatal malignancy despite more aggressive therapies. Patients with NSCLC who undergo radical surgery are few (10%) and they are likely to be cured. In advanced stage disease, first-line chemotherapy has shown little improvement in survival, and second-line chemotherapy, in few patients in good shape, has globally shown little effect. The development of novel targeted therapies has given new hope to both physicians and patients [6] . Pleural metastatic effusion in patients with NSCLC has been reclassified by the IASLC [7] as M1a disease since the outcome of these patients is generally poor [8] , and behaves like distant metastasis. Also, patients with SCLC and pleural metastasis have an intermediate prognosis between limited and diffused disease and the ‘mystery’ of this behavior should be clarified by further clinical studies [9] . In lung cancer, although the disease remains in the same hemithorax, the explanation for this ‘aggressive behavior’ of pleural inIt has been 30 years since Richard Light defined the criteria that totally changed the ‘world of pleura’, and his research still seems so fresh; no better criteria exist today to differentiate transudates from exudates. Other classic markers tested in pleural fluid by different authors have shown little accuracy in the differential diagnosis of pleural effusions even between malignant and nonmalignant effusions [1] . In the dawn of the molecular era, research is focused on new markers, such as genes, matrix metalloproteinases, and specific receptors, tested in pleural fluid either for diagnosis or to understand the mechanisms involved in pleural diseases. However, pleural fluid may not be sufficient at present to fully study the pleura, and therefore ‘tissue is the issue’ [2] . A major tool to obtain more tissue is thoracoscopy to diagnose and/or to understand the mechanisms and pathophysiology of different diseases of the pleura. A better understanding of the molecular and cellular mechanisms helps to identify new targets and therefore new compounds for effective treatment [3, 4] . The present thematic review series focuses on 6 different issues of pleural diseases. Patients with lung diseases of unknown etiology and limited effective therapy are rare (orphan) [5] but may have pleural effusion either as a presenting syndrome or during disease evolution. Little is known regarding the pathogenetic mechanisms of orphan diseases, and even less is known about the occurPublished online: January 11, 2012