The neutrophilic and fibrinolytic response to talc can predict the outcome of pleurodesis

Psathakis, Kostas; Calderón-Osuna, E.; Romero-Romero, Beatriz; Martín-Juan, José; Romero-Falcón, Auxiliadora; Rodríguez-Panadero, Francisco

doi:10.1183/09031936.06.00097505

Cited by 25 publications

(25 citation statements)

References 23 publications

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“…Commercial kits are already available to perform a rapid neutrophil count and D-dimer determination, and the measurement of those parameters will be a useful tool to monitor the ongoing biologic process after intrapleural talc instillation. Thus, patients developing a good inflammatory response show a typical pattern with rapidly increasing neutrophils and declining D-dimer activity in serial samples of pleural fluid after talc poudrage [16]. If this does not occur, or the response to talc is poor, we attempt to enhance the pleurodesis process by increasing the suction rate and prolonging the time of drainage in order to provoke a better pleural symphysis through mechanical irritation and tight apposition of the visceral and parietal pleura layers.…”

Section: Mechanisms Involved In Pleurodesismentioning

confidence: 99%

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 Involved In Pleurodesismentioning

confidence: 99%

Mechanisms of Pleurodesis

2012

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“…The interactions between inflammation and coagulation-fibrinolysis balance in the pleural space described by us and others [25,26,33], taken together with the finding of elevated levels of IL-8 in plasma of up to 44% of our patients in the present study, would suggest that after application of the pleurodesis agent IL-8 could disseminate from the inflamed pleural space into the bloodstream, thus activating the systemic coagulation. The association found between high levels of IL-8 in plasma and short survival ( fig.…”

Section: Discussionmentioning

confidence: 67%

“…For more than 20 yrs our group has been involved in investigating the mechanisms of pleural inflammation, and we have reported a close relationship between inflammation and the coagulation-fibrinolysis balance in the pleural space of patients submitted to talc pleurodesis [25]. Specifically, we found dramatically increased levels of TAT in the pleural fluid of patients with MPE who had a successful pleurodesis [26], but the possible simultaneous activation of coagulation in the systemic circulation could be a life-threatening side-effect.…”

Section: Discussionmentioning

confidence: 99%

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

Montes-Worboys¹,

Rodriguez-Portal²,

Arellano-Orden³

et al. 2009

Eur Respir J

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The aim of our study was to investigate whether interleukin (IL)-8 activates systemic coagulation after talc pleurodesis in malignant pleural effusion (MPE), and whether levels of IL-8 in plasma are related to early death after talc pleurodesis.IL-8 and tumour necrosis factor (TNF)-a were measured in samples from 231 MPE patients before and after talc pleurodesis. Whole blood from 31 healthy volunteers was incubated with IL-8, TNF-a and thromboplastin for 3 h in vitro, and thrombin-antithrombin (TAT) levels were measured. The same stimulation of blood samples was repeated using doses of calibrated talc.Nine, 12 and 17 patients died within 7, 10 and 15 days respectively. IL-8 was elevated in 102 patients within 48 h, and thrombotic events were observed in six of those patients. Survival correlated inversely with IL-8 at 24 and 48 h, and a significant correlation was also found between IL-8 and TAT. A positive dose-dependent correlation with TAT production was observed when blood was stimulated with IL-8 in vitro. However, there was no significant response to stimulation with talc, as compared with control blood samples.IL-8 is involved in the activation of coagulation that may occur after talc pleurodesis, and might also be implicated in early death of patients with MPE.

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“…This acute response is mediated by proinflammatory cytokines like IL-8 [20,21], and the relation between success of pleurodesis and inflammatory response has been analyzed in our study (fig. 3).…”

Section: Discussionmentioning

confidence: 99%

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

Arellano-Orden

Romero-Falcón²,

Juan³

et al. 2012

Respiration

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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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The neutrophilic and fibrinolytic response to talc can predict the outcome of pleurodesis

Cited by 25 publications

References 23 publications

Mechanisms of Pleurodesis

Mechanisms of Pleurodesis

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

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

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