Interleukin-8 activates coagulation and correlates with survival after talc pleurodesis

Montes-Worboys, Ana; Rodriguez-Portal, José-Antonio; Arellano-Orden, Elena; Digón-Pereiras, J.; Rodríguez-Panadero, Francisco

doi:10.1183/09031936.00146808

Cited by 25 publications

(18 citation statements)

References 34 publications

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“…We have recently reported that IL-8, which is increased in the pleural fluid after talc treatment, activates the coagulation cascade and correlates with survival after talc pleurodesis [60]. The relevance of this finding in clinical practice is still unclear, but some premature deaths following pleurodesis may be in part related to undetected thrombosis and/or pulmonary embolism, and not only to advanced neoplastic disease, as it is commonly believed.…”

Section: Mechanisms Associated With Complications Of Pleurodesismentioning

confidence: 98%

Mechanisms of Pleurodesis

2012

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Pleurodesis aims to obliterate the pleural space by producing extensive adhesion of the visceral and parietal pleura, in order to control relapse of either pleural effusions (mostly malignant) or pneumothorax. A tight and complete apposition between the two pleural layers is a necessary condition to obtain a successful pleurodesis, but – besides this mechanical aspect – there are many biological mechanisms that appear to be common to most of the sclerosing agents currently used. Following intrapleural application of the sclerosing agent, diffuse inflammation, pleural coagulation-fibrinolysis imbalance (favoring the formation of fibrin adhesions), recruitment and subsequent proliferation of fibroblasts, and collagen production are findings in the pleural space. The pleural mesothelial lining is the primary target for the sclerosant and plays a pivotal role in the whole pleurodesis process, including the release of several mediators like interleukin-8, transforming growth factor-β and basic fibroblast growth factor. When the tumor burden is high, normal mesothelial cells are scarce, and consequently the response to the sclerosing agent is decreased, leading to failure of pleurodesis. Also, the type of tumor in the pleural cavity may also affect the outcome of pleurodesis (diffuse malignant mesothelioma and metastatic lung carcinomas have a poorer response). There is general agreement that talc obtains the best results, and there are also preliminary experimental studies suggesting that it can induce apoptosis in tumor cells and inhibit angiogenesis, thus contributing to a better control of the malignant pleural effusion. There is concern about complications (possibly associated with talc but other agents as well) related to systemic inflammation and possible activation of the coagulation cascade. In order to prevent extrapleural talc dissemination, large-particle talc is recommended. Although it could – to some degree – interfere with the mechanisms leading to pleurodesis and a carefully balanced clinical decision has therefore to be made, prophylactic treatment with subcutaneous heparin is recommended during hospitalization (immediately before and after the pleurodesis procedure).

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Section: Mechanisms Associated With Complications Of Pleurodesismentioning

confidence: 98%

Mechanisms of Pleurodesis

2012

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“…If we assume that talc-associated complications occur within the first few days, the clear differences observed between groups is striking in our study (table 4). Rather than the characteristics of the population included (table 1), our study emphasizes that short survival was related to higher levels of cytokines (especially IL-8) in serum of patients receiving ST. Our group has previously demonstrated that IL-8 is involved in the activation of coagulation after talc pleurodesis, and it might also be implicated in the early death of patients with MPE [22]. On the other hand, the levels of VEGF and TAT found in the serum samples from patients of the ST group would suggest a spillover of the mediators from the pleural cavity to the systemic circulation after intrapleural talc application.…”

Section: Discussionmentioning

confidence: 91%

Small Particle-Size Talc Is Associated with Poor Outcome and Increased Inflammation in Thoracoscopic Pleurodesis

Arellano-Orden

Romero-Falcón²,

Juan³

et al. 2012

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Rationale: Talc is very effective for pleurodesis, but there is concern about complications, especially acute respiratory distress syndrome. Objectives: It was the aim of this study to investigate if talc with a high concentration of small particles induces greater production of cytokines, and if pleural tumor burden has any influence on the local production and spillover of cytokines to the systemic circulation and eventual complications. Methods: We investigated 227 consecutive patients with malignant effusion submitted to talc pleurodesis. One hundred and three patients received ‘small-particle talc' (ST; containing about 50% particles <10 µm) and 124 received ‘large-particle talc' (with <20% particles <10 µm). Serial samples of both pleural fluid and blood were taken before and 3, 24, 48 and 72 h after thoracoscopy. Also, mesothelial cells were stimulated with both types of talc in vitro. Measurements and Results: Interleukin-8, tumor necrosis factor-α, vascular endothelial growth factor, basic fibroblast growth factor and thrombin-antithrombin complex were measured in all samples. Early death (<7 days after talc) occurred in 8 of 103 patients in the ST and in 1 of 124 in the ‘large-particle talc' group (p = 0.007). Patients who received ST had significantly higher proinflammatory cytokines in pleural fluid and serum after talc application, and also in supernatants of the in vitro study. Pleural tumor burden correlated positively with proinflammatory cytokines in serum, suggesting that advanced tumor states induce stronger systemic reactions after talc application. Conclusions: ST provokes a strong inflammatory reaction in both pleural space and serum, which is associated with a higher rate of early deaths observed in patients receiving it.

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“…Anaesthesia and surgery result in changes in the dynamics of inflammatory indicators 30 . This results in activating the coagulation and fibrinolytic blood system, and triggering the cascade of the inflammatory response 31,32 . The beneficial effect of the inflammatory reaction is in its participation in the defence against infective agents.…”

Section: Discussionmentioning

confidence: 99%

The dynamics of selected local inflammatory markers to talc in the treatment of malignant pleural effusions

Habal¹,

Jankovicova²,

Omran³

et al. 2013

BIOMED PAP

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Background. Malignant pleural effusions accumulate in the space between the visceral (inner) layer covering the lungs and the parietal (outer) layer covering the chest wall. Larger effusions compress the pulmonary parenchyma resulting in increasing dyspnoea. Treatment is always local and palliative. Among others, chemical pleurodesis using talc can be performed in selected patients. Talc is hydrated magnesium silicate (chemically H 2 Mg 3 (SiO 3 ) 4 ) and has been used for pleurodesis since 1935. Videothoracoscopic talc powder insufflation (talc poudrage) is the most effective.However, markers of inflammatory reactions to extraneous substances like talc are not fully understood. The aim of this study was to assess the course of local inflammatory changes in the pleural cavity after talc insufflation. Methods. The Department of Cardiac Surgery of the Faculty of Medicine and University Hospital in Hradec Kralove, treated 47 patients aged 65 on average; 29 males and 18 females with proven recurrent malignant pleural effusion of various aetiologies from January 2009 to December 2010. They were retrospectively divided into group A (40 patients) without recurring effusion, and group B (7 patients) with recurring effusion and the need for thoracentesis or chest drainage during the 9-month monitoring. Results. Major findings were made in soluble forms of cell receptors. Group B showed statistically higher levels of the anti-inflammatory form of sCD-163 receptor in pleural fluid before the talc poudrage. This showed limited ability to create an adequate inflammatory response to external stimuli. This group also showed lower levels of the inflammatory form of sTLR-2 receptor immediately after the talc insufflation. This revealed low local reactivity to external stimuli. The effect of the treatment was not influenced by morphologic tumour type. No statistically significant differences in postoperative complications were found. This confirmed the safety of both videothoracoscopy and treatment. Conclusions. There was no correlation between the type of malignant affection and the outcome of the chemical pleurodesis. Patients with relapsing effusion have higher values of concentration of anti-inflammatory sCD-163 in pleural fluid even before the application of talc, and lower levels of concentration of inflammatory sTLR-2 immediately after application of talc.

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Interleukin-8 activates coagulation and correlates with survival after talc pleurodesis

Cited by 25 publications

References 34 publications

Mechanisms of Pleurodesis

Mechanisms of Pleurodesis

Small Particle-Size Talc Is Associated with Poor Outcome and Increased Inflammation in Thoracoscopic Pleurodesis

The dynamics of selected local inflammatory markers to talc in the treatment of malignant pleural effusions

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