Malignant Pleural Effusion

Abstract

Malignant pleural effusion (MPE) poses a significant clinical problem. Current non-etiologic management is suboptimal in terms of efficacy and safety. In light of recent research progress, we propose herein a new view of MPE development, which may rapidly translate into meaningful changes in therapeutics. In addition to tumor-induced impairment of pleural fluid drainage, pertinent findings point towards another pathway to MPE formation: a vicious loop of interactions between pleural-based tumor cells and the host vasculature and immune system that results in increased net fluid production via enhanced plasma extravasation into the pleural space. The ability of tumor cells to trigger this cascade likely rests on a specific and distinct transcriptional repertoire, which results in important vasoactive events in the pleural space. While the characterization of tumor-derived factors responsible for MPE development is in the making, an additional, indirect path to MPE was recently demonstrated: tumor cells recruit and co-opt host cells and mediators, which in turn, amplify tumor cell-primed fluid leakage and impact tumor cell functions. Importantly, recent evidence suggests that the biologic events that culminate in clinical MPE are likely amenable to therapeutic inhibition and even prevention. In this perspective, the scientific basis for an update of current concepts of MPE formation is highlighted. Key questions for future research are posed. Finally, a vision for novel, effective, safe and convenient treatment modalities that can be offered to outpatients with MPE is set forth.

Thoracic perfusion of recombinant human endostatin (Endostar) combined with chemotherapeutic agents versus chemotherapeutic agents alone for treating malignant pleural effusions: a systematic evaluation and meta-analysis

“…The evaluation was performed according to the evaluation criteria established by Cochrane Handbook (Version 5.0.1) [28]. As shown in Table 3, the results showed that 4 of the 13 studies (30.7 %) belonged to the low risk of bias [17, 20, 24, 27], and the rest [1, 4, 5, 8–10, 15, 16, 18, 19, 21–23, 25, 26, 29] were inclined to indicate an unclear risk of bias (69 %) (Table 3). …”

“…However, most of lung cancer cases are often resistant to standard chemotherapy agent, or eventually become chemoresistant. Therefore, the fact is many chemotherapeutic agents are not as effective as we expected in treating MPE via thoracic perfusion [4]. Today, novel molecular targeted drugs that have been studied to improve the cure and control rate of the disease.…”

Prostaglandin E2-mediated adenosinergic effects on CD14+cells: Self-amplifying immunosuppression in cancer

“…PE is responsible for indirectly influencing tumor cells, regulating inflammation and contributing to tumor dissemination. 19 The population of CD14 C cells in the tumor microenvironment consists of tumor-associated macrophages (TAM) and monocytes. In mesothelioma, M2 macrophages with immunosuppressive features have been observed in the tumor; their ratio (CD163/ CD68) having a negative prognostic value.…”

Mutant KRAS promotes malignant pleural effusion formation

“…MPE manifests with vascular leakiness that leads to fluid accumulation in the pleural space and is etiologically associated with fulminant inflammation and neovascularization, rather than mere tumour-induced lymphatic obstruction2. However, the reason why some patients with pleural tumours develop MPE while others do not remains unknown3.…”