Systemic Distribution of Talc After Intrapleural Administration in Rats

doi:10.1378/chest.115.1.190

Chest

Volume 115, Issue 1, January 1999, Pages 190-193

https://doi.org/10.1378/chest.115.1.190 Get rights and content

Study objectives

Many reports have shown the efficacy of talc to induce an effective pleurodesis. However, there is little information about the side effects related to this sclerosing agent. The objective of this experimental study is to recognize the systemic distribution of talc after its instillation into the pleural space of rats.

Design

Forty animals were assigned to receive talc through a catheter placed in a left minimal thoracotomy. They were randomly divided in two groups: group 1 received 20 mg of talc and group 2 received 10 mg in the same total volume of 1 mL of saline solution. Half of the animals in each group were killed 24 h and the other half 48 h after the procedure. BAL was collected and histologic sections of both lungs, chest wall, liver, kidneys, spleen, heart, and brain were examined. Crystals were tracked using polarized light and we have used a “birefringent particles index of deposition” in an attempt to quantify the amount or talc encountered in different organs.

Results

Talc crystals were found in every organ of all animals studied (100%). There was no statistical difference either on the dose of talc used or in the time of death. The amount of talc was statistically different in the organs, which made us divagate about a route of absorption.

Conclusions

We conclude that there is a progressive deposition of talc particles in the organs examined after its administration into the pleural space of normal rats. This report suggests that there is a rapid absorption of talc through the pleural surface and that the systemic distribution thereafter is not dose related. Further studies are necessary to assess the amount of crystals and the clinical correlation to these findings.

Section snippets

Experimental Design

Forty Wistar rats of similar weight (298 ± 11 g), provided by the Animal Quarters of the Faculty of Medicine—University of São Paulo, were assigned to one of the following groups: in group 1, animals received 20 mg of talc (extrapolated from the usual dose of 5 g in a 70-kg adult man); in group 2, half of this dose was employed, in the same total volume of 1 mL of saline solution. Both groups were divided in two subgroups based on the time of death; in subgroups 1a and 2a, it was performed

Results

All animals did not have any side effects and tolerated both the anesthesia and surgery well. The technique was safe, and no animal suffered any complications from the surgery.

Discussion

Several reports have been published regarding the potential risk of the indiscriminate use of talc pleurodesis. In 1956, Gaensler,² for the first time (to our knowledge), observed severe effects resulting from pleural poudrage, such as severe pain (worse than the pain observed after thoracotomy) fever, shock, prolonged hospitalization, embolization with hemiplegia, significant changes of the pleura (thickening, granulomas, fibrothorax), and loss of respiratory function. More serious outcome was

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Les pleurésies métastatiques (PM) représentent une situation fréquente dans l’évolution des cancers. Leurs conséquences, comme la dyspnée et la toux, altèrent la qualité de vie des patients et une prise en charge palliative ciblant l’amélioration de la dyspnée est l’objectif principal. Le principal mécanisme d’apparition d’une PM repose sur la diminution de la réabsorption du liquide par la plèvre pariétale (PP) en rapport avec l’envahissement des ganglions lymphatiques médiastinaux. Les autres causes englobent l’envahissement direct ou par voie hématogène de la PP. Des études récentes ont montré d’autres voies de développement des PM où l’on retrouve une boucle d’interactions entre les cellules tumorales au niveau de la plèvre et le système vasculaire et immunitaire résultant en la production de liquide dans la cavité pleurale via une extravasation plasmatique. Les options thérapeutiques courantes incluent l’évacuation du liquide par ponctions itératives ou drainage pleural. Récemment, l’utilisation de cathéters pour drainage « ambulatoire » a montré un rapport efficacité/coût favorable en diminuant le séjour hospitalier et une amélioration de la qualité de vie (QDV) des patients. L’autre option thérapeutique repose sur l’oblitération de la cavité pleurale par un agent symphysant. Le talc dédié, administré à travers un drain thoracique ou pulvérisé au cours d’une thoracoscopie, est le plus efficace. Toutefois, toutes ces méthodes thérapeutiques donnent des résultats sousoptimaux et ont des inconvénients. Le rôle de l’extravasation plasmatique dans une plèvre « hyperperméable » doit être pris en compte. Les cellules mésothéliales et endothéliales inflammatoires au sein de la cavité pleurale interagissent avec les cellules tumorales, conduisant à la formation d’une PM. Les médiateurs impliqués dans cette cascade biologique seront les nouvelles cibles pour le traitement des PM.
Metastatic pleural effusion (MPE) is a frequent feature of advanced cancer. Consequences of MPE, such as dyspnea and cough, deteriorate the patient's quality of life and palliation, aiming alleviation of breathlessness, is one of the major goal of therapy. One of the commonest mechanisms for the development of MPE is the inability of the parietal pleura to reabsorb pleural fluid because of involvement of mediastinal lymph nodes. The other possible causes include direct tumor invasion and hematogenous spread to the parietal pleura. Recent studies have shown another pathway to MPE formation involving a loop of interactions between pleural-based tumor cells and the host vasculature and immune system resulting in increased fluid production via enhanced plasma extravasation into the pleural space. Current therapeutic options include removal of the pleural fluid by iterative thoracentesis or pleural drainage. Recently the use of long-term indwelling pleural catheter have shown to be a cost-efficient procedure allowing outpatient or minimal hospital stay improving patients’quality of life. The other current method for the treatment of MPE aims to obliterate the pleural cavity. Talc is the gold-standard for a chemical pleurodesis through a chest tube or during a thoracoscopy procedure. However all these standard palliative methods are suboptimal with few drawbacks leading to consider the role of excessive plasma leakage through hyperpermeable pleural network as critical mechanism for MPE formation. Inflammatory mesothelial and endothelial cell in the pleural environment interact with tumor cells leading to MPE formation. The new targets for the treatment of MPE in the future will be several mediators enrolled in this biological cascade.
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Laboratory and Animal InvestigationsSystemic Distribution of Talc After Intrapleural Administration in Rats

Study objectives

Design

Results

Conclusions

Section snippets

Experimental Design

Results

Discussion

J Thorac Surg

J Thorac Cardiovasc Surg

Chest

Chest

Chest

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Ann Thorac Surg

Ann Thorac Surg

J Thorac Cardiovasc Surg

Chest

Am J Surg

Laboratory and Animal Investigations
Systemic Distribution of Talc After Intrapleural Administration in Rats