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Acute zinc deficiency and trabecular bone loss in rats with talc granulomatosis.

Subcutaneous inflammation induced by magnesium silicate (talc) leads to the suppression of bone elongation, osteoblast insufficiency, and subsequent bone loss in rats. Since bone and immunological changes in talc granulomatosis are similar to those observed in zinc deficiency, we investigated the kinetics of zinc tissue distribution and the effects of zinc supplementation on the development of bone loss in rats with talc-induced inflammation. Decrease in serum zinc concentration was observed between 5 and 15 h in rats with talc granulomatosis. It was paralleled by the accumulation of zinc in the liver and rapid disappearance of osteoblasts from the trabecular bone surfaces. However, talc-injected rats supplemented parenterally and orally with zinc sulfate exhibited a decrease in osteoblast trabecular surface comparable to that of unsupplemented rats bearing granulomas despite normalized serum zinc concentrations. Zinc supplementation slightly increased osteoblast trabecular surface in all supplemented groups, but this effect was not significant. We conclude that zinc is the earliest indicator of the acute-phase response in rats with talc granulomatosis. Although zinc appears to be important for the normal function of bone cells, there is no causative relationship between acute zinc deficiency and decreased osteoblast number and activity in rats with talc granulomatosis.

Acute-Phase Reaction↗

An epidemiological study of talc-related respiratory morbidity among employees of a rubber industry in Shiraz-Iran.

OBJECTIVES: The main purpose of this study was to assess and characterize the pulmonary reactions associated with occupational exposure to talc dust. METHODS: Ninety-seven talc workers and 110 unexposed employees as the reference group were randomly selected from a local rubber industry. Standardized respiratory questionnaires were administered to the subjects, they underwent chest X-ray and were examined by a specialist for any possible respiratory abnormality to be diagnosed. Furthermore, pulmonary function tests (PFTs) were measured just before and after the work shift. Moreover, to assess the extent to which workers had been exposed to talc dust, using standard methods, inhalable and respirable dust concentrations were measured in different dusty worksites. RESULTS: The average (mean +/- SD) age (years), weight (kg), height (cm) and duration of exposure to talc dust (years) for the exposed group were 35.8 +/- 6.75, 73.1 +/- 9.2, 172.3 +/- 5.9 and 11.79 +/- 5.3, respectively. The corresponding values for the non-exposed group were 36.1 +/- 6.87, 73.36 +/- 8.1, 173.2 +/- 5.7 and 0 +/- 0, respectively. Atmospheric concentrations of inhalable and respirable talc dust were estimated to be 41.8 +/- 23.52 and 19.8 +/- 8.04 mg/m(3) (mean +/- SD), respectively. Talc exposed subjects had a significantly higher prevalence of respiratory symptoms. Similarly, PFTs revealed that exposure to this lubricating agent was associated with significant decreases in the mean percentage predicted of vital capacity (VC), forced vital capacity (FVC) and forced expiratory volume in the first second (FEV(1)). Likewise, there was a general tendency for VC, FVC and FEV(1) to decrease as estimated cumulative exposure (years worked) increased. Moreover, there was an acute reduction in some parameters of pulmonary function such as VC, FVC and FEV(1), over the work shift. Chest radiographs of exposed workers showed that pneumoconiosis profusions were between p 0/0 and p 2/1 according to the ILO 1980 chest X-ray classification. CONCLUSIONS: These results that are in full agreement with our preliminary observations, support the notion that occupational inhalation exposure to talc is associated with both acute and chronic respiratory disorders and induces bronchitis and interstitial lung disease.

Adult↗

Influence of the morphogranulometry and hydrophobicity of talc on its antisticking power in the production of tablets.

Antisticking power varies according to the talc considered. It is difficult to define the physical properties of talc implicated in its antisticking power. In this work, different talcs were characterized and an evaluation made of their performance in reducing sticking in tablet manufacturing. Determination of the specific surface area was made by permeametry, morphogranulometric analysis by laser diffractometry using a method, which made it possible to assess the mean thickness of talc particles, and measurement of water absorption kinetics was taken to assess hydrophobicity. The relationship between the characteristics of talcs and their antisticking power was then considered. There is a correlation between the particle size of talc and surface hydrophobicity. The detaching force of tablets appears to be dependent on the basal dimension of talc.

Hydrophobic and Hydrophilic Interactions↗

Respiratory failure following talc pleurodesis.

BACKGROUND: Sterile talc is currently the agent of choice for pleurodesis. Its success rate is excellent, and talc is generally well tolerated. However, a recent experience with fulminant pneumonitis following talc pleurodesis prompted a review of our experience. METHODS: A retrospective review of patients undergoing talc pleurodesis at our institution between December 1993 and December 1997 was performed, documenting respiratory and other complications. Statistical analysis was performed using Student's t test and Pearson correlations. RESULTS: Seventy-eight patients received 89 talc pleurodesis procedures. Respiratory complications or death occurred in 33%; 9% of patients developed adult respiratory distress syndrome. There was no statistical difference in outcomes between patient groups, methods of application, or talc dosages utilized. CONCLUSIONS: This series revealed a significantly higher rate of serious complications than that reported in the current literature, without implicating a clear reason for these outcomes. Our data raise questions about the safety of talc pleurodesis.

Aged↗

Serious complications with talc slurry pleurodesis.

OBJECTIVE: Talc is a highly efficacious and commonly employed agent for chemical pleurodesis, which has generally been felt to be well tolerated. However, increasing reports of adult respiratory distress syndrome (ARDS) have heightened safety concerns. A recent case of ARDS prompted us to review our experience with talc pleurodesis. METHODOLOGY: We conducted a retrospective review of all patients who received talc slurry pleurodesis at Green Lane Hospital, Auckland, New Zealand, between 1 January 1998 and 31 December 1999 and documented all complications occurring within 48 h of the procedure. RESULTS: Thirty-three talc pleurodesis were performed on 29 patients, most commonly for a malignant pleural effusion. Complications occurred in 15 patients (52% of procedures). Minor complications included tachycardia (n = 11; 33%), pain (n = 9; 27%), fever (n = 8; 24%) and dyspnoea (n = 4; 12%). Major complications occurred in seven patients with hypoxaemia and hypotension. Two of these patients died; one death directly attributable to ARDS, the other hastened by a talc pleurodesis-related tachycardia. CONCLUSIONS: These results challenge the assumption that talc pleurodesis is a safe procedure. There were a significant number of serious complications, including a death, from ARDS. Physicians and patients should be aware that complications occur frequently after talc pleurodesis which may be life-threatening or fatal.

Adult↗

A prospective, randomised study comparing the efficacy of talc slurry and bleomycin in the treatment of malignant pleural effusions.

In comparative studies with other agents, insufflated talc has been shown to be the most effective agent in achieving chemical pleurodesis in patients with malignant pleural effusions. The objective of this study is to compare the efficacy of talc administered as slurry (5 g in 50 mL saline) via tube thoracostomy with that of bleomycin (1 mg/kg in 50 mL saline) (which is the most effective agent other than talc). In a randomised, prospective comparative study, twenty-six consecutive patients with proven malignant pleural effusions (recurrent after at least two pleuroscenteses) in whom no pleurodesis attempt had yet been made, and who were symptomatic, had a Karnovski index < or = 50, and an expected survival of one year or less, were included. Therapeutic failure was defined as recurrent pleural fluid > or = 50% of initial volume or requiring pleurocentesis. Recurrence rates (25% vs 21.4%, NS), fever (25% vs 35.7%, NS), pain (0% both groups) and survival (3.75 +/- 3 vs 5.82 +/- 7.15 months, NS) did not differ between bleomycin or talc treated patients. There were no major complications (e.g., empyema) or side-effects. In conclusion, talc slurry and bleomycin are equally effective in achieving chemical pleurodesis via thoracostomy in patients with malignant pleural effusions, and the safety profile of both agents is similar. Since talc is substantially less expensive than bleomycin, talc slurry probably represents the agent of choice for chemical tube thoracostomy pleurodesis.

Adult↗

Talc in liver tissue of intravenous drug abusers with chronic hepatitis. A comparative study.

To determine the frequency of talc microcrystals in liver tissue of intravenous (IV) drug abusers and the significance of this finding, the authors reviewed, with light and polarizing microscopy, sections of liver tissue from 70 patients with chronic hepatitis and a history of active (45) or past (25) IV drug abuse. Birefringent crystalline particles consistent with talc were found in 44 cases (63%), 31 associated with active and 13 with past drug abuse. The microcrystals were situated predominantly in hypertrophied portal macrophages; there were no well-formed granulomas. Scanning electron microscopic and energy-dispersive spectrophotometry performed on eight of the positive cases showed the characteristic "flake-pastry" appearance and chemical composition (silicon and magnesium) of talc. For comparison, the authors similarly examined 70 cases of posttransfusion chronic hepatitis, all of which had negative findings for talc, and 70 cases of chronic hepatitis with no documented risk factors for viral hepatitis, of which two had positive findings for talc, even though IV drug abuse was denied by the two patients. The authors conclude that talc is frequently present in the liver of IV drug abusers and whenever encountered it strongly suggests IV drug abuse. Only two patients (1.4%) with a negative history also had talc.

Adult↗

Frequency and distribution of talc contamination in patients with silicone gel-filled breast implants.

Talc was found to contaminate peri-implant scars in patients with silicone gel-filled breast prostheses resulting from the physical interaction between implant and surgical glove. This study reports the frequency and distribution of the problem and its relationship to changes in glove manufacture. Peri-implant scar tissue, obtained from a population with breast implants, was evaluated for talc. Patients were considered positive if more than two talc particles were seen intracellularly in more than two microscopic fields. The largest Texas glove manufacturer stopped using talc in 1983. Patients were grouped to demonstrate the difference in talc exposure in Texas after this manufacturing change. Of those receiving implants before 1984, 136 of 140 were positive for talc. Of those receiving implants after 1983, 24 of 54 were positive (p < 0.000; RR = 42.5; CI: 13.7-131.6). Widespread prevalence of contamination was evidenced by findings of talc in patients from various facilities, different surgeons, and multiple sites within Texas.

Adolescent↗

Talc-induced expression of C-C and C-X-C chemokines and intercellular adhesion molecule-1 in mesothelial cells.

Treatment of symptomatic carcinomatous pleural effusions is primarily directed at local palliation with a wide variety of sclerosing agents, of which talc is considered to be the most successful. The mechanism whereby talc achieves this effect is unknown. The objective of this study was to investigate whether talc stimulates pleural mesothelial cells (PMC) to release C-X-C and/or C-C chemokines and express adhesion molecules that initiate and amplify the inflammatory process in the pleural space. When PMC were challenged with talc in vitro, interleukin-8 (IL-8) and monocyte chemotactic protein-1 (MCP-1) levels were increased (p < 0.001) both at the protein and the mRNA level as compared with unstimulated cultures. Talc-stimulated PMC culture supernatant showed chemotactic activity for neutrophils and monocytes. The chemotactic activity of PMC culture supernatant was blocked by 44.2% with IL-8-specific antibody and by 55.7% with MCP-1-specific antibody, demonstrating that PMC-derived chemokines are bioactive. Talc also enhanced intercellular adhesion molecule-1 (ICAM-1) expression in PMC. The data demonstrate that talc stimulates PMC to release chemokines and express adhesion molecules that may play a critical role in pleurodesis.

Analysis of Variance↗

Agglomeration of Ibuprofen with talc by novel crystallo-co-agglomeration technique.

The purpose of this research work was to obtain directly compressible agglomerates of ibuprofen with talc by a novel crystallo-co-agglomeration (CCA) technique, which is an extension of spherical crystallization. Ibuprofen-talc agglomerates were prepared using dichloromethane (DCM)-water as the crystallization system. DCM acted as a good solvent for ibuprofen as well as a bridging liquid for agglomeration of crystallized drug with talc. The agglomerates were characterized by differential scanning calorimetry, powder X-ray diffraction, and scanning electron microscopy and were evaluated for tableting properties and for drug release. The process yielded spherical agglomerates containing ~95% to 96% wt/wt of ibuprofen. Agglomerates containing talc showed uniform distribution of hydroxypropylmethylcellulose and decreased crystallinity, and deformed under pressure. The miniscular form of ibuprofen and the hydrophobicity of talc governed the drug release rate. The batch containing a higher proportion of talc showed zero-order kinetics and drug release was extended up to 13 hours. The CCA technique developed in this study is suitable for obtaining agglomerates of drug with talc as an excipient.

Chemistry, Pharmaceutical↗

Prospective randomized trial of talc slurry vs bleomycin in pleurodesis for symptomatic malignant pleural effusions.

OBJECTIVE: Symptomatic malignant pleural effusions are common sequelae in patients with certain malignancies. Pleurodesis via bedside thoracostomy is the current treatment option most commonly used. To our knowledge, this is the first prospective randomized trial to examine which agent, bleomycin or talc slurry, is superior in terms of effectiveness, safety, and cost. PATIENTS AND METHODS: Between July 1992 and March 1995, 35 patients presenting to our medical center with symptomatic malignant pleural effusions were prospectively randomized to undergo chemical pleurodesis with either bleomycin or talc slurry via bedside thoracostomy. The conditions of patients were assessed and graded before and after treatment concerning pain, dyspnea, and chest radiographs. RESULTS: Twenty-nine patients who underwent 33 treatments (14 with bleomycin and 19 with talc) were available for follow-up. Follow-up ranged from 2 weeks to 8 months (mean, 1.7 months). Both groups demonstrated notable improvement in both pain and dyspnea following treatment, but there were no statistically significant differences between groups in the amount of improvement (two-tailed Student's t test). Permanent control of effusions, defined objectively on chest radiograph, was achieved with 11 bleomycin treatments (79%) and 17 talc treatments (90%) (p=0.388). The procedures were well tolerated and no significant adverse effects were observed. Talc is a much less costly agent than bleomycin ($12.36 cost to our medical center per treatment for talc vs $955.83 for bleomycin). CONCLUSION: Given the similar efficacy and significant cost advantage, we conclude that talc is the agent of choice when utilizing pleurodesis for control of symptomatic malignant pleural effusions.

Aged↗

Silver nitrate is superior to talc slurry in producing pleurodesis in rabbits.

STUDY OBJECTIVE: The ideal agent for producing pleurodesis has not been identified. Although talc is the agent most commonly used at the present time, there are concerns about its safety. Silver nitrate is a possible alternative agent. The purpose of the present study was to compare the effectiveness of intrapleural silver nitrate and talc slurry in producing pleurodesis in rabbits. Additionally, the total amount of pleural collagen and the distribution of thick and thin collagen fibers were studied. DESIGN: Two groups of 10 rabbits received either 0.50% silver nitrate or 400 mg/kg talc in a total volume of 2 mL intrapleurally. The animals were killed 28 days after injection, and the pleural spaces were assessed grossly for evidence of pleurodesis and microscopically for evidence of inflammation and fibrosis. Collagen was assessed with the van Gieson's and picrosirius stains. RESULTS: The macroscopic pleurodesis (scale, 0 to 4; mean +/- SEM) resulting from the intrapleural injection of silver nitrate (3.4+/-0.2) was significantly better (p<0.001) than that resulting from talc (1.6+/- 0.1). The mean degree of microscopic pleural fibrosis induced by silver nitrate (3.3+/-0.3) was significantly higher (p = 0.003) than that induced by talc (1.8+/-0.1). The mean amount of microscopic pleural collagen (van Gieson's) was significantly greater (p<0.001) in the rabbits that received silver nitrate (3.0+/-0.2) than in those that received talc (1.6+/-0.2). The distribution of thick and thin collagen fibers did not differ between the groups. CONCLUSIONS: We conclude that, in our rabbit model, intrapleural silver nitrate was more effective than talc in producing a pleurodesis.

Animals↗

Experimental pleurodesis in rabbits induced by silver nitrate or talc: 1-year follow-up.

STUDY OBJECTIVE: To compare the pleurodesis results from the intrapleural injection of silver nitrate and talc slurry over an observation period of 12 months in rabbits. DESIGN: Rabbits were randomized to receive 2 mL of 0.5% silver nitrate or 400 mg/kg of talc slurry in 2 mL intrapleurally. Ten rabbits in each group were killed at 1 month, 2 months, 4 months, 6 months, 8 months, 10 months, and 12 months after intrapleural injection. The degree of gross pleurodesis and the amount of microscopic pleural fibrosis and inflammation were graded on a scale of 0 to 4. RESULTS: The mean +/- SEM gross pleurodesis score in the 70 rabbits that received silver nitrate was 3.34 +/- 0.08, which was significantly higher than the score of 2.32 +/- 0.09 in the 70 rabbits that received talc. The mean gross pleurodesis score was significantly higher at each of the observation times (p < 0.05), except at 2 months, in the rabbits that received silver nitrate. The pleurodesis was distributed throughout the thorax in the rabbits that received silver nitrate, while it was only in the ventral thorax in the rabbits that received talc slurry. The gross pleurodesis scores showed no tendency to decrease during the 12-month observation period in either treatment group. The persistence of talc in the pleural space did not lead to chronic inflammatory changes because the inflammation scores were similar in both groups at all observation times. The microscopic pleural fibrosis score tended to decrease with time in the silver nitrate group but not in the talc slurry group. CONCLUSIONS: The intrapleural injection of 2 mL of 0.5% silver nitrate produces a better pleurodesis than does the intrapleural injection of 400 mg/kg of talc slurry in rabbits. The pleurodesis induced by silver nitrate persists for at least 1 year. The efficacy of silver nitrate as a sclerosing agent in humans should be evaluated.

Animals↗

Intrapleural low-dose silver nitrate elicits more pleural inflammation and less systemic inflammation than low-dose talc.

STUDY OBJECTIVES: Several systemic effects have been described after talc pleurodesis. The aim of this study was to assess the systemic response induced by low, nonpleurodesis-inducing doses of talc and silver nitrate in an experimental model in rabbits. DESIGN: Groups of six rabbits were injected intrapleurally with talc, 100 mg/kg or 400 mg/kg, and silver nitrate, 0.1% or 0.5%. After 6, 24, or 48 h, samples of blood and pleural fluid were collected and assayed for leukocytes, percentage of neutrophils, lactate dehydrogenase, interleukin-8, and vascular endothelial growth factor (VEGF) levels. Preinjection blood samples were used as normal blood controls. MEASUREMENTS AND RESULTS: Silver nitrate 0.1% induced a more intense pleural inflammation than that produced by talc 100 mg/kg. In contrast, talc 100 mg/kg induced a more pronounced acute systemic response with higher values of WBCs and neutrophils, whereas silver nitrate 0.1% produced no significant increases in leukocytes or neutrophils. The serum interleukin-8 and VEGF levels increased in all groups, and decreased with time only in the silver nitrate 0.1% group. The highest serum VEGF levels were observed in the talc 100 mg/kg group. CONCLUSIONS: In conclusion, 0.1% silver nitrate produced an intense pleural inflammatory response with a less evident systemic response in comparison to 0.5% silver nitrate and talc 100 mg/kg or 400 mg/kg.

Animals↗

Systemic inflammatory reaction after thoracoscopic talc poudrage.

BACKGROUND: Recent studies have reported fever as a side effect of talc poudrage during thoracoscopic pleurodesis. However, thoracoscopy itself is likely to induce systemic inflammatory reaction, as it is an interventional procedure. The aim of the study was to investigate whether systemic inflammatory response is due to talc poudrage or to thoracoscopy. METHODS: We prospectively studied two groups of patients. The first group (18 patients) underwent thoracoscopic talc poudrage, and the second group (17 patients) underwent only diagnostic thoracoscopy. We measured body temperature, as well as WBC count and C-reactive protein (CRP) levels before the procedure (baseline), and at 24 and 48 h after the procedure. No antiinflammatory medication was permitted to be used before, during, or after the procedure. All patients had a 3-month follow-up. RESULTS: The baseline patient characteristics were similar in both groups. Temperature increased significantly in the thoracoscopic talc poudrage group (overall comparison, p = 0.005) especially at 9, 12, and 24 h after the procedure. Overall, the WBC count (p = 0.004), percentage of neutrophils (p = 0.03), and CRP levels (p < 0.0001) were significantly increased in the group of patients who underwent thoracoscopic talc poudrage. On the contrary, lymphocytes were significantly decreased (overall comparison, p = 0.01) in the thoracoscopic talc poudrage group during the same period. Mild side effects, such as pain during and after thoracoscopy and subcutaneous emphysema, were noted. No severe complication, such as infection or acute respiratory failure, was noted in either group during the hospitalization or during the follow-up period. CONCLUSION: According to our results, fever and systemic inflammatory reaction is due to talc poudrage and not to thoracoscopy.

Acute-Phase Reaction↗

Effectiveness of silver nitrate compared to talc slurry as pleural sclerosing agent in rabbits. Influence of concomitant intrapleural lidocaine.

UNLABELLED: The ideal agent for producing pleurodesis has not been identified. Talc, the most commonly used, poses several problems. Another possibility is silver nitrate, which was widely used in the past. PURPOSE: To determine the influence of the intrapleural instillation of lidocaine in producing a pleurodesis with silver nitrate, to define the effect of lidocaine in the maturation of the collagen fibers, and to confirm that the pleurodesis after silver nitrate is stronger than after talc. METHODS: We studied three groups of 8 rabbits. Two groups received 0.5% silver nitrate; in one we had previously injected 0.5 ml of 2% lidocaine. The third group received 400 mg/kg talc (2 ml). The animals were sacrificed 28 days after the injection, and the pleural spaces were assessed grossly for evidence of pleurodesis and microscopically for evidence of inflammation and fibrosis. The total amount of pleural collagen and the distribution of thick and thin collagen fibers were quantified. Collagen was identified using picrosirius red stain. RESULTS: In the two groups that received silver nitrate (without lidocaine: 3.5 + 03 and with lidocaine: 3.2 + 0.3), the macroscopic pleurodesis (scale 0 - 4) was significantly (p = 0.001) better than that resulting from talc (1.6 + 0.2). The mean degree of pleural fibrosis induced by silver nitrate (3.5 + 0.2) was significantly (p = 0.004) higher than that induced by talc (1.9 + 0.1). The previous instillation of lidocaine resulted in a tendency for decreased amounts of fibrosis (3.1 + 0.4). The mean amount (10(3)mm2) of pleural collagen was significantly (p = 0.009) greater in the rabbits that received silver nitrate (116.9 + 22.7) than in those that received talc (10.7 + 3.4). The injection of lidocaine slightly reduced the collagen (80.1 + 30.3). The distribution of collagen fibers did not differ among the groups. CONCLUSION: This rabbit model clearly confirms that intrapleural silver nitrate is more effective than talc for producing pleurodesis. The previous intrapleural instillation of lidocaine results in a decreasing trend in the amount of collagen, but does not change the effectiveness of the pleural fusion or modify the process of collagen maturation.

Anesthetics, Local↗

[The effects of intrapleural anti-TNFalpha antibody on chemical pleurodesis induced by talc slurry or doxycycline].

OBJECTIVE: To determine whether the intrapleural injection of TNFalpha neutralizing Fab antibody fragment (anti-TNFalpha Fab) would prevent the pleurodesis that occurs after the intrapleural injection of talc or doxycycline. METHODS: In a randomized blinded placebo controlled study, 34 New Zealand white rabbits were given 400 mg/kg talc or 10 mg/kg doxycycline intrapleurally as a sclerosant via a chest tube. Half of the rabbits in each group were also given polyclonal affinity purified anti-TNFalpha Fab 2 000 units or saline as placebo immediately before and 12 hours after the injection of the sclerosants. Chest tube were aspirated at 12 hours intervals until their removal at 4 days. Rabbits were sacrificed at 28 days. The pleural fluid volume, cell counts, LDH and pleurodesis scores were compared among groups. RESULTS: Both talc and doxycycline produced an exudative pleural effusion. The pleural fluid volume and LDH levels were significantly greater in the doxycycline group than talc group. However, the pleural fluid leukocyte counts in talc group were higher than doxycycline group. The administration of anti-TNFalpha Fab had no significant effect on pleural fluid volume, LDH or leukocyte counts in either groups. However, the intrapleural administration of anti-TNFalpha Fab results in a significant decrease in the pleurodesis score for the talc group than doxycycline group (1.8 +/- 0.9 vs 3.2 +/- 0.8). In contrast the pleurodesis score was virtually identical in the doxycycline group with (3.5 +/- 0.5) and without (3.4 +/- 0.7) anti-TNFalpha Fab. CONCLUSION: The intrapleural administration of anti-TNFalpha Fab diminishes the pleurodesis induced by talc but not that which results from doxycycline. These findings suggest that different mechanisms are involed with the two different sclerosants.

Animals↗

Perineal application of cosmetic talc and risk of invasive epithelial ovarian cancer: a meta-analysis of 11,933 subjects from sixteen observational studies.

OBJECTIVE: Prior epidemiological studies suggest an association between perineal cosmetic talc use and increased risk of epithelial ovarian cancer. A meta-analysis was performed to evaluate this suspected association. MATERIALS AND METHODS: Using previously described methods, a protocol was developed for a meta-analysis examining the association between perineal talc use versus non-use and the development of invasive epithelial ovarian cancer. Literature search techniques, study inclusion criteria and statistical procedures were prospectively defined. Data from observational studies were pooled using a general variance based meta-analytic method employing confidence intervals previously described by Greenland. The outcome of interest was a summary relative risk (RRs) reflecting the risk of ovarian cancer development associated with perineal talc use versus non-use. Sensitivity analyses were performed when necessary to explain any observed statistical heterogeneity. RESULTS: Sixteen observational studies meeting protocol specified inclusion criteria were located via a comprehensive literature search. These studies enrolled a total of 11,933 subjects. Analysis for heterogeneity demonstrated that the data were homogenous (p = 0.17) and could be combined in a meta-analysis. Pooling all sixteen studies yielded a RRs of 1.33 (CI = 1.16-1.45), a statistically significant result suggesting a 33% increased risk of ovarian cancer with perineal talc use. Despite this finding, the data showed a lack of a clear dose-response relationship making the RRs of questionable validity. Further sensitivity analyses showed that hospital-based studies showed no relationship between talc use and ovarian cancer risk, i.e. RRs 1.19 (0.99-1.41) versus population-based studies (RRs = 1.38, CI = 1.25-1.52). This suggests that selection bias and/or uncontrolled confouding may result in a spurious positive association between talc use and ovarian cancer risk in population-based studies. CONCLUSION: The available observational data do not support the existence of a causal relationship between perineal talc exposure and an increased risk of epithelial ovarian cancer. Selection bias and uncontrolled confouding may account for the positive associations seen in prior epidemiological studies.

Female↗