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Talc pleurodesis: talc slurry versus thoracoscopic talc insufflation in a porcine model.

BACKGROUND: Pleurodesis using both talc slurry and thoracoscopic talc insufflation has been shown to be clinically effective. This study compares these two modalities of pleural talc instillation in an animal model. METHODS: Eleven immature pigs underwent general endotracheal anesthesia. On one side, a slurry of 5 g sterile United States Pharmacopeia talc in 50 mL of saline solution was instilled through a thoracostomy tube. On the other side, the lung was deflated and 5 g of dry talc was insufflated under thoracoscopic visualization. The animals were sacrificed 30 days later, and the quality of pleural adhesions was graded from 0 to 2 (0 = absent; 1 = light; 2 = dense) in each of six regions of each hemithorax. The distribution of adhesions on each side was graded from 0 to 6, according to the number of areas that contained adhesions. RESULTS: One animal died of anesthetic complications. Among the survivors, adhesions produced by both methods were dense and diffuse in 8 of 10 animals, and light and diffuse in 1 animal. One animal had light or absent adhesions on the talc slurry side, and dense and diffuse adhesions on the thoracoscopic talc insufflation side. There was no difference between the techniques for density of adhesion scores (talc slurry, 9.9 +/- 2.2; thoracoscopic talc insufflation, 10.0 +/- 2.5) or distribution of adhesion scores (talc slurry, 5.5 +/- 1.0; thoracoscopic talc insufflation, 5.8 +/- 0.4) (p > 0.1). CONCLUSIONS: Effective pleurodesis in a porcine model can be obtained with either talc slurry or thoracoscopic talc insufflation.

Animals↗

Influence of talc dose on extrapleural talc dissemination after talc pleurodesis.

This study was designed to ascertain, in a rabbit model, extrapleural talc deposition and the related inflammatory response after talc slurry pleurodesis with two clinical doses, 200 and 50 mg/kg. Histopathologic evaluations revealed that whereas numerous rabbits receiving a high dose had talc in the ipsilateral (70%) and contralateral (55%) lung, mediastinum (90%), pericardium (30%), and liver (25%), a small number of animals treated with a low dose showed talc in the ipsilateral lung (10%) and mediastinum (20%) and none in the contralateral lung, pericardium, or liver. Hematologic and immunocytochemical analyses showed that a systemic inflammatory response develops shortly after pleurodesis with a high talc dose involving massive accumulation of neutrophils and macrophages in lung tissue. Zymography also revealed that the pulmonary expression of matrix metalloproteinases 2 and 9 was up-regulated in both lungs in a dose-dependent manner soon after talc instillation. Furthermore, microscopic examination of lung specimens revealed that the higher the dose of talc, the greater the development of both fibrotic visceral pleural thickening and foreign-body granulomas. These findings show pleurodesis with a high talc dose to be associated with an increased risk of extrapleural talc deposition, which may originate undesirable acute and chronic inflammatory responses.

Acute Disease↗

Influence of particle size on extrapleural talc dissemination after talc slurry pleurodesis.

BACKGROUND: Cases of acute respiratory failure reported after talc pleurodesis have raised concerns about its safety. It has been speculated that this pulmonary inflammatory syndrome is secondary to the extrapleural dissemination of the talc particles. STUDY OBJECTIVES: To test the hypothesis that particle size influences extrapleural talc deposition and pleural inflammation after talc slurry pleurodesis. DESIGN: Thirty rabbits underwent pleurodesis as follows: 10 rabbits received 200 mg/kg of the talc used for human pleurodesis, normal talc (NT); 10 rabbits received 200 mg/kg of talc with particles of larger size, large talc (LT); and 10 rabbits received saline solution. Samples from the ipsilateral lung, chest wall, diaphragm, mediastinal pleura, heart, liver, spleen, and right kidney were obtained at 24 h and 7 days and processed for optic and electron microscopy and energy-dispersive x-ray analysis. RESULTS: Visceral pleural thickening was greater with NT than with LT, but no differences were observed in the macroscopic score of adhesions. There was more talc in the lungs of the rabbits that received NT than in those that received LT. Talc particles were detected in mediastinum (100%) and pericardium (20%), irrespective of the talc used. Three animals, all receiving NT, had talc particles in the liver. CONCLUSIONS: Our study shows that while both talcs were equally effective in achieving pleurodesis, the intrapleural injection of NT elicits greater pulmonary and systemic talc particle deposition than LT. Moreover, pleural inflammation was greater with NT than with LT.

Animals↗

Talc deposition and effects after 20 days of repeated inhalation exposure of rats and mice to talc.

The relationship between the inhalation exposure concentration of talc and the resulting lung burdens and histologic lesions was studied using groups of 20 F344/Crl rats and 20 B6C3F mice (10 male and 10 female) exposed to one of three concentrations of asbestos-free talc for 6 hr/day, 5 days/week for 4 weeks. Controls were exposed to filtered air using the same schedule. The pulmonary retention of talc and the development of pulmonary pathology were evaluated. The mass median aerodynamic diameter (MMAD) of the talc aerosol was 3.0 microns with a geometric standard deviation (sigma g) of 1.9. The mean exposure concentrations for rats were 0, 2.3, 4.3, and 17 mg talc/m3. Lung burdens in rats averaged 0, 0.07, 0.17, and 0.72 mg talc/g lung after the 20-day inhalation exposure; thus, the amount retained in the lung per unit of exposure concentration increased with increasing concentration. Mean exposure concentrations for the mice were 0, 2.2, 5.7, and 20.4 mg of talc/m3, which resulted in lung burdens of 0, 0.10, 0.29, and 1.0 mg talc/g lung; thus, the relationship between exposure concentration and the amount retained in the lung was approximately constant. Lung burdens from this study were used to project lung burdens that would result from longer exposures of rodents and man. No clinical signs were observed in the rats or mice prior to sacrifice 24 hr after the last exposure day. Histologic alterations in lung tissue consisted of only a modest, diffuse increase of talc-containing, free macrophages within alveolar spaces in both rat and mouse groups exposed to the highest level of talc for 20 days. A model simulating chronic talc inhalation exposure of rats and mice predicted lung burdens of 2-3 mg talc/g lung (wet wt) if animals were exposed to 17 mg talc/m3 for 2 years, and deposition and clearance of talc were unchanged by continued exposure. A potential limitation in this modeling is that if clearance of talc is delayed by continued exposure, the accumulated talc lung burdens would be higher than those projected by the simulation model. Humans exposed to aerosols of respirable talc are projected to accumulate much higher lung burdens than would occur in rodents exposed to the same aerosol, because humans have a higher estimated deposition fraction and slower estimated clearance of the deposited talc dust. Equilibrium lung burdens of greater than or equal to 2 mg talc/g lung were predicted for human exposures at or near the TLV for talc.

Aerosols↗

The relationship between perineal cosmetic talc usage and ovarian talc particle burden.

OBJECTIVE: Epidemiologic studies support the hypothesis of a dose-related risk of epithelial ovarian cancer with perineal talc usage exposure. Frequency and duration of talc has not been previously correlated with ovarian talc content. STUDY DESIGN: Ovaries were studied from 24 women undergoing incidental oophorectomy who were interviewed regarding talc usage. Twelve subjects reported frequent perineal talc applications; the twelve controls reported no use. Ovarian tissue blocks were digested and analyzed by polarized light microscopy and analytic electron microscopy to identify and quantify talc. RESULTS: Talc was identified in all 24 cases by either light or electron microscopy. Talc particle counts were completely unrelated to reported levels of perineal talc exposure. CONCLUSIONS: The detection of talc in all ovaries demonstrates that it can reach the upper genital tract. Widespread exposure to talc during diapering may contribute to the ubiquitous presence of talc in ovarian tissue.

Adult↗

Thoracoscopic talc insufflation versus talc slurry for symptomatic malignant pleural effusion.

BACKGROUND: Talc has been generally accepted to be the most effective sclerosant for chemical pleurodesis, although the optimal route of administration remains unclear. METHODS: We designed a prospective, randomized study to compare video-assisted thoracoscopic talc insufflation with bedside talc slurry in the treatment of malignant pleural effusion. From September 1993 to November 1995, 57 patients were recruited and randomized to either video-assisted thoracoscopic talc insufflation under general anesthesia (n = 28) or talc slurry by the bedside (n = 29). Patients with poor general condition (Karnofsky score less than 30%), poor pulmonary function (forced expiratory volume in 1 second less than 0.5 L), or trapped lungs were excluded from this study. Five grams of purified talc was used for either video-assisted thoracoscopic talc insufflation or talc slurry. RESULTS: There was no statistically significant difference between the two groups of patients with respect to age, sex ratio, chest drainage duration, postprocedural hospital stay, parenteral narcotics requirement, complications, or procedure failure (ie, recurrence). CONCLUSIONS: Video-assisted thoracoscopic talc insufflation has not been shown to be a superior approach compared with talc slurry in our study. Because the former demands more resources, we advocate that talc slurry should be considered as the procedure of choice in the treatment of symptomatic malignant pleural effusion in patients who do not have trapped lungs.

Aged↗

Method for determining the lung burden of talc in rats and mice after inhalation exposure to talc aerosols.

A method has been developed to quantitate talc lung burdens in rats and mice after inhalation exposure to talc aerosols. The method is based on acid-insoluble magnesium (Mg) determination by flame atomic absorption. Precipitating protein from homogenates of lungs of unexposed rodents with 5% perchloric acid and washing with 5% trichloroacetic acid removed the soluble and naturally occurring Mg. This resulted in residual Mg content averaging 0.43 micrograms Mg per g lung in rats and less than 0.1 microgram Mg per g lung in mice for young rodents less than 12 weeks old. Rodents 12-18 months old had residual mean (+/- SD) Mg contents of 3.4 +/- 2.0 micrograms Mg per g rat lung (n = 17) and 6.5 +/- 2.9 micrograms Mg per g mouse lung (n = 12). Thus, the background residual acid-insoluble Mg content in rodent lungs appears to increase with age. Negligible quantities of Mg were extracted directly from the talc treated by these procedures. Adding 50-2000 micrograms talc to lungs from unexposed rodents, followed by the sample treatment, gave mean (+/- SD) Mg recoveries of 89 +/- 12% (n = 19) for rat lungs and 96 +/- 26% (n = 15) for mouse lungs. The lung burden of talc in rodents exposed to talc aerosols for 6 h per day, 5 days per week for 4 weeks was determined. Mean lung burdens in rats were 77, 187, and 806 micrograms talc per g lung (n = 10) for exposures at 2.3, 4.3, and 17 mg talc m-3, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Aerosols↗

Talc poudrage versus talc slurry in the treatment of malignant pleural effusion. A prospective comparative study.

OBJECTIVE: The aim of this study was to investigate the effectiveness, safety and appropriate mode of administration of intrapleural talc for pleurodesis, in the treatment of malignant pleural effusion (MPE). METHODS: Prospective not randomized trial was conducted to compare thoracoscopic talc poudrage (TP) with tube thoracostomy and talc slurry (TS) for the local control of malignant pleural effusion. Both procedures were previously standardized; 6g of talc was administered for each procedure. Only the patients with lung re-expansion after drainage entered the study. Patients at high risk for general anaesthesia, poor general conditions and short life-expectancy received talc slurry through a chest tube, at the bedside. All the other patients underwent videothoracoscopic talc poudrage, with a pneumatic atomizer, under general anaesthesia. Morbidity, 30-day freedom from recurrence and long-term results were assessed and the two groups were compared. RESULTS: One hundred and nine patients entered the study (72 TP, 37 TS). Sixty-three patients in the TP group (87.5%) and 27 in the TS group (73%) had an immediate successful pleurodesis (p = 0.049); 53 patients (88.3%) and 16 patients (69.6%) had a successful pleurodesis 90 days after the procedure; 59 patients (81.9%) and 23 patients (62.2%), respectively, had a life-long pleural symphysis (p = 0.023). Adverse effects were generally mild: chest pain (36.1% in TP patients, 48.6% in TS patients) and fever (38.8% and 35.1%, respectively) were the more common but the difference was not significant between the two groups. We observed neither acute respiratory failure nor mortality due to the procedure. CONCLUSIONS: Our study confirms that intrapleural talc carries good results in the treatment of malignant pleural effusion. TP was significantly more effective than TS; both methods were safe but TS had a higher incidence of thoracic pain during the procedure. Talc pleurodesis should be offered to every patient with MPE, apart from terminally ill ones, provided that a satisfying lung re-expansion has been achieved. TP should be performed whenever possible; otherwise, a slurry bedside procedure will be worthwhile, even in patients with low performance status (PS), though poorer results have to be expected. A careful selection is essential to define the proper technique.

Adult↗

Cosmetic talc should not be listed as a carcinogen: comments on NTP's deliberations to list talc as a carcinogen.

Concerns that cosmetic talc might be carcinogenic are addressed and shown to lack persuasive scientific support. These concerns are based (1). on several, but not all, retrospective epidemiological, statistically barely significant case-control studies of questionable biological import (Their results lack dose-response relationships, are inconsistent and ambiguous, and are therefore inconclusive. Whether inanimate talc particles can translocate from the perineum to the ovaries, a precondition if they were to cause ovarian cancer, remains unresolved.); (2). on one inhalation study in animals whose results, according to a panel of experts, "cannot be considered as relevant predictors of human risk," a position shared by other experts in the field; and (3). on elevated incidence of lung cancer in pottery workers. These workers were occupationally exposed several decades ago to nowadays impermissible concentrations of aerosols comprising a multitude of industrial dusts. To construe a risk for the consumer of pure cosmetic or pharmaceutical-grade talc under consumer conditions, based on these findings, lacks scientific support. Talc is not genotoxic, is not carcinogenic when injected into ovaries of rats, does not cause cancer decades after pleurodesis, and induces apoptosis in vitro in human mesothelioma cells but not in normal mesothelial cells. There is no credible evidence of a cancer risk from inhalation of cosmetic talc by humans. Considering talc a carcinogen lacks convincing scientific documentation.

Animals↗

Distribution of talc suspension during treatment of malignant pleural effusion with talc pleurodesis.

Talc pleurodesis is an effective technique for the management of symptomatic malignant pleural effusions. It is assumed that a good dispersion of talc suspension contributes to the final success of this treatment. For this purpose, guidelines often advise to rotate the patient after intra-pleural instillation of the sclerosant. This prospective, randomized study analyses the dispersion of talc suspension and the overall success rate in patients with malignant effusions. After instillation of 99mTc-sestamibi-labeled talc suspension ten subjects were rotated for 1 h, while the ten other patients remained in a stable supine body position. Scintigraphic imaging was done in two directions immediately after instillation and after 1 h with a clamped drain. The overall success of the treatment was assessed 1 month after the pleurodesis. The dispersion of talc was limited and unequal in 75% of the subjects. In two patients with apparently good distribution on anterior views, the lateral views of the scintigraphy showed only limited distribution. Rotation of the patients did not influence the dispersion of sludge after 1 min or 1 h. Pleurodesis was successful in 85% of the patients after 1-month follow-up. Standard rotation protocols for patients with malignant pleural effusion do not affect the overall dispersion of talc suspension and should be abolished because of the discomfort caused to the patients.

Adult↗

Phase III intergroup study of talc poudrage vs talc slurry sclerosis for malignant pleural effusion.

STUDY OBJECTIVE: To demonstrate the efficacy, safety, and appropriate mode of instillation of talc for sclerosis in treatment of malignant pleural effusions (MPEs). DESIGN: A prospective, randomized trial was designed to compare thoracoscopy with talc insufflation (TTI) to thoracostomy and talc slurry (TS) for patients with documented MPE. MEASUREMENTS: The primary end point was 30-day freedom from radiographic MPE recurrence among surviving patients whose lungs initially re-expanded > 90%. Morbidity, mortality, and quality of life were also assessed. RESULTS: Of 501 patients registered, those eligible were randomized to TTI (n = 242) or TS (n = 240). Patient demographics and primary malignancies were similar between study arms. Overall, there was no difference between study arms in the percentage of patients with successful 30-day outcomes (TTI, 78%; TS, 71%). However, the subgroup of patients with primary lung or breast cancer had higher success with TTI than with TS (82% vs 67%). Common morbidity included fever, dyspnea, and pain. Treatment-related mortality occurred in nine TTI patients and seven TS patients. Respiratory complications were more common following TTI than TS (14% vs 6%). Respiratory failure was observed in 4% of TS patients and 8% of TTI patients, accounting for five toxic deaths and six toxic deaths, respectively. Quality-of-life measurement demonstrated less fatigue with TTI than TS. Patient ratings of comfort and safety were also higher for TTI, but there were no differences on perceived value or convenience of the procedures. CONCLUSIONS: Both methods of talc delivery are similar in efficacy; TTI may be better for patients with either a lung or breast primary. The etiology and incidence of respiratory complications from talc need further exploration.

Adult↗

[Use of talc and sarcoidosis - pathogenic role of cutaneous talc exposure in sarcoidosis].

INTRODUCTION: We report on two patients with sarcoidosis with disseminated nodes, who used talc on irritated cutaneous areas. CASE REPORT: A histologic examination with intense polarised light showed up cristalline bi-refringent particles within vessels in contact with granulomatous areas. Microdissection followed by an electronic microscopy study and microanalysis was realised. In situ microanalysis allowed us to identify bi-refringent particles with a size of roughly 0.25microm as silica or silicate coming possibly from talc. We consequently studied a brand name talc. The diffraction spectrum showed that this product not only contained talc but also chlorite and quartz. Electron microscopy examination showed particles of all sizes even smaller than 0.25microm. These infra-microscopic particles, visible in a vessel only when agglomerated, could be invisible under optic microscopy (resolution: roughly 0.5microm) inside the granuloma even though they are responsible for it. Moreover, at this level of size of particles, they may escape mineralogic analyses which use methods involving the destruction of organic material, the mineral residue collecting on cellulose filter with a diameter generally of 0.45microm. CONCLUSION: Two recent epidemiologic studies confirm the possible role of mineral exposure in sarcoidosis. Some sarcoidosis could be caused by mineral overload on genetically predisposed patients. Some cases could be related to mineral powder application. Among different types of mineral exposure, applications of cosmetic products may induce disseminated granulomatous reaction on genetically predisposed patients. Such applications have to be considered in epidemiologic studies.

Adult↗

Preparation, characterization, and dissolution studies of ibuprofen solid dispersions using polyethylene glycol (PEG), talc, and PEG-talc as dispersion carriers.

Solid dispersions of ibuprofen (IBF) were prepared by solvent evaporation method using polyethylene glycol 10000 (PEG), talc, and PEG-talc as dispersion carriers. The drug-carrier(s) interactions in the solid state were investigated using scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and x-ray diffraction analysis. Interactions in the solution were studied by performing dissolution experiments. No important and well-defined chemical interaction was found between the ingredients. The increase in the IBF dissolution rate from the solid dispersions with the carriers used in this study could be attributed to several factors such as improved wettability, local solubilization, and drug particle size reduction.

Calorimetry, Differential Scanning↗