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In many cases, pleurodesis is the only treatment available for the treatment of malignant pleural effusion (MPE), and in the case of excessive daily pleural effusion, its therapeutic effect may be reduced. In this study, we intended to investigate the therapeutic effects and safety of octreotide in patients with MPE undergoing pleurodesis with talc powder.This study was a single-center, placebo-controlled, and triple-blind, randomized trial designed to investigate the therapeutic effects and safety of octreotide in patients with MPE in Tehran, Iran, from March 2020 to March 2021. Patients with MPE were randomly divided into two parallel groups, one receiving subcutaneous octreotide (3 doses of 50 µg/day) and the other receiving placebo before and after pleurodesis with talc powder. The patients were followed up with a chest X-ray 1 week, 1 month, and 3 months later. The primary outcome measures of this study were the amount of discharge from the chest tube before and after pleurodesis and the length of hospital stay. Treatment failure, relapse, pleural effusion analysis, and side effects were considered the secondary outcome measures of the study.A total of 46 patients (23 in the octreotide group and 23 in the placebo group) with MPE was included in this study. Our findings demonstrated that adjunctive treatment with subcutaneous octreotide increases the efficacy of pleurodesis with talc powder. We showed that compared to the placebo group, patients in the octreotide group have significantly decreased production of pleural effusion both before (p = 0.009) and after (p = 0.002) pleurodesis. Octreotide treatment led to a decreased hospital stay (p = 0.004 before pleurodesis and p = 0.001 after pleurodesis) and reduced treatment failure (p = 0.022). However, octreotide did not decrease the relapse at 1-week, 1-month, and 3-month follow-ups. Moreover, octreotide did not affect pleural effusion parameters compared to placebo. Ultimately, our results also showed that treatment with octreotide was safe and did not have significant side effects.Our findings demonstrated that adjunctive treatment with subcutaneous octreotide increases the efficacy of pleurodesis with talc powder without any significant side effects. Future studies with a larger sample size and longer follow-up time can confirm the results of this study and also determine the appropriate dose of octreotide for the treatment of MPE.Iranian Registry of Clinical Trials, IRCT20210915052492N1. Registered 11 October 2021 - Retrospectively registered, https://www.irct.ir/trial/58776 .

Titanium dioxide (in the form of E171) is a ubiquitous excipient in tablets and capsules for oral use. In the coating of a tablet or in the shell of a capsule the material disperses visible and UV light so that the contents are protected from the effects of light, and the patient or caregiver cannot see the contents within. It facilitates elegant methods of identification for oral solid dosage forms, thus aiding in the battle against counterfeit products. Titanium dioxide ensures homogeneity of appearance from batch to batch fostering patient confidence. The ability of commercial titanium dioxide to disperse light is a function of the natural properties of the anatase polymorph of titanium dioxide, and the manufacturing processes used to produce the material utilized in pharmaceuticals. In some jurisdictions E171 is being considered for removal from pharmaceutical products, as a consequence of it being delisted as an approved colorant for foods. At the time of writing, in the view of the authors, no system or material which could address both current and future toxicological concerns of Regulators and the functional needs of the pharmaceutical industry and patients has been identified. This takes into account the assessment of materials such as calcium carbonate, talc, isomalt, starch and calcium phosphates. In this paper an IQ Consortium team outlines the properties of titanium dioxide and criteria to which new replacement materials should be held.

This article summarizes the clinical guidelines for the diagnosis and treatment of malignant pleural effusion (MPE) sponsored by the Spanish Society of Thoracic Surgery (SECT). Ten clinical controversies were elaborated under the methodology of PICO (Patient, Intervention, Comparison, Outcome) questions and the quality of the evidence and grading of the strength of the recommendations was based on the GRADE system. Immunocytochemical and molecular analyses of pleural fluid may avoid further invasive diagnostic procedures. Currently, the definitive control of MPE can be achieved either by pleurodesis (talc poudrage or slurry) or the insertion of a indwelling pleural catheter (IPC). It is likely that the combination of both techniques (i.e., thoracoscopy with talc poudrage and insertion of a IPC, or instillation of talc slurry through a IPC) will have a predominant role in the future therapeutic management.

An 85-year-old ex-smoker being managed conservatively over 2 years for a small right apical pneumothorax presented to the respiratory clinic with suddenly worsening shortness of breath and chest pain. A chest radiograph demonstrated sudden deterioration in the size of his pneumothorax. Previous CT scans had found emphysematous cystic changes within the lungs, and his new presentation warranted definitive surgical intervention with a right bullectomy and talc pleurodesis through a video-assisted thoracoscopic surgery procedure. The patient made a good recovery and was discharged from clinic a year later. This case demonstrates the importance of follow-up in patients with unresolved pneumothoraces due to the potential for sudden deterioration, and highlights the significance of respecting patient involvement and autonomy in the decision-making process.

Background Risk of ovarian cancer in women with frequent perineal talcum powder product is not well understood. Prior systematic reviews focused on ever use. The purpose of this study is to estimate the association between frequent (at least 2 times per week) perineal talcum powder use and ovarian cancer. Methods A systematic review and meta-analysis was conducted according to meta-analysis of observational studies in epidemiology guidelines. Study protocol was prospectively registered at PROSPERO (registration number CRD42020172720). Searches were performed in PubMed, Embase, Web of Science, and Cochrane Central Register of Controlled Trials databases from their inception to August 2, 2021. Case-control and cohort studies were included if they reported frequent perineal talcum powder use and an adjusted odds ratio or hazard ratio for ovarian cancer. Review for inclusion, data extraction, and quality assessment (using the Newcastle-Ottawa Scale [NOS]) were performed independently by two reviewers. Pooled adjusted odds ratios with 95% confidence intervals were generated from the random effects model. Heterogeneity was quantified with I2 statistic. Funnel plot and Eger’s test were performed to assess publication bias. Subgroup and sensitivity analyses were performed for testing the robustness of the overall findings. Results Initial database searches returned 761 unique citations and after review, eleven studies describing 66,876 patients, and 6542 cancers were included (Cohen’s κ = 0.88). Publication quality was high (median NOS = 8, range: 4 to 9). Frequent talcum powder use was associated with an elevated risk of ovarian cancer (adjusted pooled summary odds ratio 1.47 (95% CI 1.31, 1.65, PI2= 24%, P=0.22). There was no meaningful difference limiting analysis to publications with a NOS quality score of 8 or 9 or limiting studies based on study design. Conclusions This review suggests an increased risk of ovarian cancer associated with frequent perineal powder exposure of 31–65%.

Objective: Empyema is a complication of talc-pleurodesis that may lead to further surgical intervention and death. Therefore, the present study’s objective was to identify the risk factors for the development of post-pleurodesis empyema after talc slurry pleurodesis in order to better select patients for this procedure and minimize its morbidity. Methods: Patients with malignant pleural effusion who underwent talc slurry pleurodesis at the present institution from January 2018 to January 2020 were retrospectively analyzed. Post-pleurodesis empyema was defined as pleural infection up to 30 days after pleurodesis. Using Cox regression analysis, significant prognostic factors for the development of empyema were examined. Results: Of the 86 patients identified for inclusion in the study, 62 were women (72%). Their mean age was 56.3±12.6 years. The median pleural drainage time was 9 days, and 20 patients (23.3%) developed empyema. In the univariate analysis, both drainage time (p = 0.038) and the use of antibiotics prior to pleurodesis (p < 0.001) were risk factors for pleural empyema. Multivariate analysis also identified the use of antibiotics as an independent risk factor (Odds Ratio [OR] 9.81; 95% Confidence Interval [95% CI] 2.87–33.54). Although the pulmonary expansion was not associated with empyema in the multivariate analysis, patients with less than 50% pulmonary expansion had a 4.5-times increased risk of empyema (95% CI 0.90-22.86; p = 0.067), and patients with 50–70% pulmonary expansion had a 3.8-times increased risk of empyema (95% CI 0.98–15; p = 0.053) after pleurodesis. Conclusion: The study suggests that antibiotic therapy prior to talc slurry pleurodesis may increase the risk of developing empyema. Furthermore, pleurodesis should be considered with caution in patients with long-duration chest tube placement and incomplete lung expansion.

RATIONALE: Tunneled, indwelling pleural catheters (IPC) have been demonstrated to be an effective method of managing malignant pleural effusions. However, they allow pleurodesis and can therefore be removed in only a subset of patients. A novel, silver-nitrate coated IPC was developed with the intention of creating a rapid, effective chemical pleurodesis to allow more frequent and earlier catheter removal. This study represent the pivotal clinical trial evaluating that catheter vs the standard IPC.OBJECTIVES: To compare the efficacy of a novel silver nitrate-eluting indwelling pleural catheter (SNCIPC) with that of a standard, uncoated catheter.METHODS: The SWIFT trial was a multicentre, parallel-group, randomised, controlled, patient-blind trial. Central randomisation occurred following a computer-generated schedule, stratified by site. Recruitment was from 17 secondary or tertiary-care hospitals in the USA and 3 in the UK and included adult patients with malignant pleural effusion needing drainage, without evidence of lung entrapment or significant loculation. The intervention group underwent insertion of a SNCIPC with maximal fluid drainage, followed by a tapering drainage schedule. The control group received a standard, uncoated catheter. Follow up was until 90 days. The primary outcome measure was pleurodesis efficacy, measured by fluid drainage, at 30 days.RESULTS: 119 patients were randomised. 5 withdrew before receiving treatment, leaving 114 (77 SNCIPC, 37 standard IPC) for intention-to-treat analysis. Mean age was 66 years (SD 11). More patients in the SNCIPC group were in-patients (39% vs 14%, p=0.009). For the primary outcome, pleurodesis rates were 12/37 (32%) in the control group and 17/77 (22%) in the SNCIPC group (rate difference -0.10, 95% CI -0.30-0.09). Median time to pleurodesis was 11 days (IQR 9-23) in the control group and 4 days (IQR 2-15) in the SNCIPC group. No significant difference in treatment-related adverse event rates was noted between groups.CONCLUSIONS: The SNCIPC did not improve pleurodesis efficacy compared to a standard indwelling pleural catheter. This study does not support the wider use of the SNCIPC device. Clinical trial registered with ClinicalTrials.gov (NCT02649894).

Background: The current cost of treatment of malignant pleural effusion (MPE) with an indwelling pleural catheter (IPC) is unclear. Objective: We propose a review of the scientific evidence on the ...

Inhaled particles that are poorly soluble or insoluble and of low toxicity (“poorly soluble low toxicity” or “PSLT” particles), can accumulate in the lung and at lung overload levels induce lung cancers in rats. The question of whether PSLT particles increase lung cancer risk in humans is complicated by large differences between rats and humans and the relatively large particle doses administered in animal studies even when compared with heavy human occupational exposures. We review the findings of epidemiological studies on occupational exposure to each of three different PSLT particles (carbon black, talc and taconite). The epidemiological evidence indicates that at even very high occupational exposure levels at which non-malignant respiratory diseases including pneumoconiosis and even talcosis are observed, lung cancer risks appear not to be elevated. Although positive human cancer risks might be predicted based on extrapolation from overload doses in rats to relevant exposures in humans, the epidemiological “reality check” based on the three examples indicates that these PSLT particles are unlikely to increase lung cancer risk in humans even at high occupational levels of exposure. Therefore, we propose that careful evaluation of the epidemiological evidence can serve as a “reality check” for human risk assessment and help balance the risk evaluation process.

The first indwelling pleural catheter (IPC) received Federal Drug Administration approval in 1997, nearly 40 years after John Chambers first described instillation of talc into the pleural space for palliation of malignant pleural effusions. Since then IPCs have revolutionized the management of malignant pleural effusions, providing an effective means of controlling dyspnea in the end stages of life without the pain and prolonged hospital stays long associated with chemical sclerosing agents. While palliation of symptoms is the primary purpose of IPCs, development of pleurodesis in the outpatient setting is often an important secondary goal. Historically, decisions regarding IPC drainage frequency have been largely arbitrary and only recently has the evidence started to emerge regarding the effects of specific drainage strategies on both symptom control and pleurodesis development. This focused clinical review explores the current literature regarding IPC drainage strategies as well as novel methods designed to improve the efficacy of IPCs in a thorough and systematic manner. In addition, this review provides an in-depth analysis and synthesis of the data focusing on key considerations needed to develop patient-centered and cost-effective strategies for the use of IPCs in malignancy.

Background/aim The objectives of this study were to evaluate systemic inflammation using different sclerosing agents and to estimate the prediction of systemic inflammation for the efficacy of pleurodesis. Patients and methods Ninety-six patients with recurrent and symptomatic malignant pleural effusion were enrolled in this retrospective study. We used serum C-reactive protein (CRP) levels, serum leukocyte counts and neutrophil-to-lymphocyte ratios (NLRs) as parameters of systemic inflammatory reactions. Evaluations of these parameters were performed before and 24 h after pleurodesis. Results Pleurodesis was successful in 81 (84.4%) patients. The non-graded talc induced the highest changes in serum CRP levels, total white blood cell and neutrophil counts compared to other agents, while mitoxantrone induced the lowest. Graded talc and bleomycin induced the same levels of changes in serum CRP levels and serum leukocyte counts. The change in serum NLR was the same for all agent groups. Logistic regression confirmed that a change in serum CRP levels [odds ratio (OR)=0.92, p=0.002] and previous chemotherapy (OR=3.31, p=0.012) were independent predictors of pleurodesis efficacy. Conclusion Pleurodesis agents induced a systemic inflammatory response at different levels. The change in serum CRP levels could be useful for predicting the success of pleurodesis.

This narrative review aims to describe and compare different interventional methods for the management of recurrent malignant pleural effusion and offers perspectives for the future era.Dyspnea as a result of the recurrent malignant pleural effusion is one of the main factors decreasing the quality of life in patients with oncologic diseases. To date, there is no strict guideline for the management of malignant pleural effusions.Several different techniques are available to prevent production of the effusion or to provide intermittent drainage, however, the principle of these methods remains palliative. The choice of treatment in any patient depends mainly on the preferences of the patient, speed of the fluid production, expandability of the lung, and predicted survival of the patients. The interventional methods of managing malignant pleural effusions are described in detail, including thoracocentesis, chemical pleurodesis, talc poudrage pleurodesis, slurry pleurodesis, thoracoscopic procedures, indwelling pleural catheters, implantable pleural ports, and pleuroperitoneal shunting.Pleurodesis and fully implantable devices such as pleural ports may become the most useful techniques in the future, mainly because of better comfort for the patients and no need for repeated pleural punctures (Ref. 55).

Background: The objective of this nationwide, registry-based study was to compare the two most frequently used procedures for the palliative treatment of a malignant pleural effusion (MPE) and to evaluate differentiated indications for these two procedures. Methods: This was a retrospective observational study based on data of the “PLEURATUMOR” registry of the German Society for Thoracic Surgery. Patients who were documented in the period from January 2015 to November 2021 and had video-assisted thoracic surgery (VATS) talc pleurodesis or implantation of an indwelling pleural catheter (IPC) were included. Results: A total of 543 patients were evaluated. The majority suffered from secondary pleural carcinomatosis (n = 402; 74%). VATS talc pleurodesis (n = 361; 66.5%) was performed about twice as often as IPC implantation (n = 182; 33.5%). The duration of surgery was significantly shorter in IPC-patients with 30 min compared to VATS talc pleurodesis (38 min; p = 0.000). Postoperative complication rate was 11.8% overall and slightly higher after VATS talc pleurodesis (n = 49; 13.6%) than after IPC implantation (n = 15; 8.2%). After VATS talc pleurodesis patients were hospitalized significantly longer compared to the IPC group (6 vs. 3.5 days; p = 0.000). There was no significant difference in postoperative wound infections between the groups (p = 0.10). The 30-day mortality was 7.9% (n = 41). Conclusion: The implantation of an IPC can significantly shorten the duration of surgery and the hospital stay. For this reason, the procedure should be matched with the patient's expectations preoperatively and the use of an IPC should be considered not only in the case of a trapped lung. CA extern

Objective In the present study, we describe the features and functional properties of a new powder cosmetic ingredient, an amorphous mesoporous magnesium carbonate (MMC, also named Upsalite®) with regard to physical characteristics as well as functional attributes. Methods Physical and functional characterization of MMC, as compared to other common powder cosmetic ingredients (silica, mica, kaolin, talc and starch), was assessed using nitrogen gas adsorption, powder X‐ray diffraction, particle size distribution by laser diffraction, scanning electron microscopy (SEM), and oil and moisture uptake tests. The powder ingredients were also applied on human skin and analysed for short‐ and long‐term mattifying effect, and a new method was developed to measure flashback effect. MMC was tested for skin irritation using an in vitro cell model as well as in vivo, through the Human Repeated Insult Patch Test on 50 human volunteers. Results Mesoporous magnesium carbonate has a high surface area and pore volume. It has an excellent absorption capacity and can take up both oil and water simultaneously. It provides instant and long‐lasting mattifying effect when applied on human skin without drying or irritating skin and exhibits no measured flashback effect. Conclusion Mesoporous magnesium carbonate has good sensory and visual characteristics as well as excellent absorbing and mattifying properties, suggesting that it has great potential to replace other powder ingredients currently used as fillers and absorbers in powder cosmetics., Color, feel, application and special visual effects along with long wear are the main properties behind all types of powders. MMC has good sensory and visual characteristics as well as excellent absorbing and mattifying properties, suggesting that it has great potential to replace or compliment other powder ingredients currently used as fillers and absorbers in powder cosmetics.

Asbestos recently returned to the spotlight when Johnson & Johnson halted sales of baby powder due to lawsuits claiming that the talc in baby powder may have been contaminated with asbestos, which has been linked to the risk of ovarian cancer development. Although talc and asbestos have some structural similarities, only asbestos is considered causally associated with ovarian cancer by the WHO’s International Agency for Research on Cancer. While it is useful to understand the types and properties of asbestos and its oncologic biology, the history of its association with ovarian cancer is largely based on retrospective observational studies in women working in high asbestos exposure environments. In reviewing the literature, it is critical to understand the distinction between associative risk and causality, and to examine the strength of association in the context of how the diagnosis of ovarian cancer is made and how the disease should be distinguished from a similar appearing but unrelated neoplasm, malignant mesothelioma. Based on contextual misinterpretation of these factors, it is imperative to question the International Agency for Research on Cancer’s assertion that asbestos has a clear causal inference to ovarian cancer. This has important clinical implications in the way patients are conceivably counseled and provides motivation to continue research to improve the understanding of the association between asbestos and ovarian cancer.

Background/purpose: Talc powder is widely used in various industries, but the carcinogenic effects associated with talc are not well understood. The objective of this study was to estimate the risk of stomach cancer after occupational talc exposure. Methods: We conducted a meta-analysis was performed to calculate the meta-relative risk (mRR) of stomach cancer. We searched the MEDLINE, EMBASE, CNKI and Wanfang Data databases for publications prior to January 1, 2017 using talc, cancer, and mortality as the search terms. Only cohort studies with occupational talc exposure and stomach cancer statistics were included. Results: All pooled analyses were based on random-effects models. We selected 13 observational studies (12 publications) for the meta-analysis, and heterogeneity was observed among studies. Workers exposed to all forms of talc had a significantly increased mRR of 1.21 (95% CI: 1.03—1.42, p = 0.02) for stomach cancer. Workers exposed to talc not containing asbestiform fibers also had an increased mRR of 1.26 (95% CI: 0.97—1.63, p = 0.09). Conclusion: The available data showed a positive association between occupational talc exposure and risk of stomach cancer. The association between talc not containing asbestiform fibers and risk of stomach cancer was not significant. Further epidemiological studies are required to evaluate the safety of talc. Keywords: Talcum powder, Asbestos, Gastric cancer, Mortality

Purpose Many patients diagnosed with advanced cancer have malignant pleural effusion that does not respond to chemotherapy or radiation therapy. These patients often have respiratory symptoms, especially dyspnea. In order to relieve these symptoms, various procedures including chemical pleurodesis have been performed. Although talc is the most widely used and effective sclerosing agent, there it has various adverse effects. The objective of this study was to determine whether Viscum (ABNOVA Viscum® Fraxini Injection, manufactured by ABNOVA GmbH, Germany) could be used as an agent to replace talc in clinical practice. Methods Data of 56 patients with malignant pleural effusion who received chemical pleurodesis after tube thoracostomy from January 2003 to December 2017 were retrospectively reviewed to analyze clinical course and response after pleurodesis with each agent. Results After pleurodesis, changes in numeric rating scale (NRS) was 1.4 ± 1.6 in the talc group and 0.5 ± 1.5 in the Viscum group (p = 0.108). Changes in white blood cell counts after pleurodesis were 4154.8 ± 6710.7 in the talc group and 3487.3 ± 6067.7 in the Viscum group (p = 0.702). Changes in C-reactive protein (CRP) were 9.03 ± 6.86 in the talc group and 6.3 ± 7.5 in the Viscum group (p = 0.366). The success rate of pleurodesis was 93.3% in the talc group and 96% in the Viscum group (p = 0.225). Conclusion Viscum pleurodesis showed comparable treatment results with talc pleurodesis while its adverse effects such as chest pain and fever tended to be relatively weak.

Two cases with diagnosis of mesothelioma were referred to our laboratories with a request for tissue burden analysis in order to determine the presence of ferruginous bodies and uncoated elongated mineral particles in tissue samples. The individuals shared in common a past background of working in tile manufacturing facilities where industrial talc was used in the production of the products. Both were found to have ferruginous bodies in their lung tissues as well as elongated talc fibers/ribbons and elevated numbers of noncommercial amphiboles in their tissues. To our knowledge, this is the first report of tissue assessment for the presence of elongated mineral particles in individuals whose exposures to talc occurred were while working in the manufacture of tile products and who developed the fiber-related cancer - mesothelioma.

To assess potential mesothelioma risk following inhalation of cosmetic talc, we updated previous iterations of a pooled cohort analysis, post-study statistical power analysis, and confidence interval function analysis for a pooled cohort of international cosmetic talc miners/millers given new Italian cohort data.Five cohorts of cosmetic talc miners/millers were pooled. Expected numbers of mesotheliomas for each cohort were reported by the original authors. We based our post-study statistical power analysis on anThe pooled cohorts generated a total observation time of 135,524.38 person-years. Overall, 4.14 mesotheliomas were expected (mid-value estimate), though only one case of mesothelioma has been confirmed in the pooled cohort to date. We calculated 71% and 87% post-study power to detect a 2.5-fold or greater and a 3.0-fold or greater increase in mesothelioma, respectively. Our complimentary confidence interval function analysis demonstrated that the probability that the true mesothelioma SMR for the pooled cohort was at or above 2.0 or at or above 3.0 was 0.00235 and 0.00005, respectively.Based on the updated results of our various analyses, the current epidemiological evidence from cosmetic talc miner/miller cohort studies continues to not support the hypothesis that the inhalation of cosmetic talc is associated with an increased risk of mesothelioma.

Background Pleurodesis is done as an in-patient procedure to control symptomatic recurrent malignant pleural effusion (MPE) and has a success rate of 75–80%. Thoracic ultrasonography has been shown in a small study to predict pleurodesis success early by demonstrating cessation of lung sliding (a normal sign seen in healthy patients, lung sliding indicates normal movement of the lung inside the thorax). We aimed to investigate whether the use of thoracic ultrasonography in pleurodesis pathways could shorten hospital stay in patients with MPE undergoing pleurodesis. Methods The Efficacy of Sonographic and Biological Pleurodesis Indicators of Malignant Pleural Effusion (SIMPLE) trial was an open-label, randomised controlled trial done in ten respiratory centres in the UK and one respiratory centre in the Netherlands. Adult patients (aged ≥18 years) with confirmed MPE who required talc pleurodesis via either a chest tube or as poudrage during medical thorascopy were eligible. Patients were randomly assigned (1:1) to thoracic ultrasonography-guided care or standard care via an online platform using a minimisation algorithm. In the intervention group, daily thoracic ultrasonography examination for lung sliding in nine regions was done to derive an adherence score: present (1 point), questionable (2 points), or absent (3 points), with a lowest possible score of 9 (preserved sliding) and a highest possible score of 27 (complete absence of sliding); the chest tube was removed if the score was more than 20. In the standard care group, tube removal was based on daily output volume (per British Thoracic Society Guidelines). The primary outcome was length of hospital stay, and secondary outcomes were pleurodesis failure at 3 months, time to tube removal, all-cause mortality, symptoms and quality-of-life scores, and cost-effectiveness of thoracic ultrasonography-guided care. All outcomes were assessed in the modified intention-to-treat population (patients with missing data excluded), and a non-inferiority analysis of pleurodesis failure was done in the per-protocol population. This trial was registered with ISRCTN, ISRCTN16441661. Findings Between Dec 31, 2015, and Dec 17, 2019, 778 patients were assessed for eligibility and 313 participants (165 [53%] male) were recruited and randomly assigned to thoracic ultrasonography-guided care (n=159) or standard care (n=154). In the modified intention-to-treat population, the median length of hospital stay was significantly shorter in the intervention group (2 days [IQR 2–4]) than in the standard care group (3 days [2–5]; difference 1 day [95% CI 1–1]; pInterpretation Thoracic ultrasonography-guided care for pleurodesis in patients with MPE results in shorter hospital stay (compared with the British Thoracic Society recommendation for pleurodesis) without reducing the success rate of the procedure at 3 months. The data support consideration of standard use of thoracic ultrasonography in patients undergoing MPE-related pleurodesis. Funding Marie Curie Cancer Care Committee

Objective: To evaluate the associations between 10 well-established ovarian cancer risk factors and risk of ovarian cancer among women with vs. without endometriosis. Design: Pooled analysis of 9 case-control studies in the Ovarian Cancer Association Consortium. Setting: Population-based. Patient(s): We included 8,500 women with ovarian cancer, 13,592 control women. Intervention(s): Ten well-established ovarian cancer risk factors. Main Outcome Measure(s): Risk of ovarian cancer for women with and without endometriosis. Result(s): Most risk factor-ovarian cancer associations were similar when comparing women with and without endometriosis, and no interactions were statistically significant. However, body mass index (BMI) 25–2 was associated with increased ovarian cancer risk among women with endometriosis (odds ratio [OR] = 1.27, 95% confidence interval [CI] 1.00–1.60), but not associated with the risk among women without endometriosis (OR = 0.97; 95% CI, 0.91–1.05) when compared with BMI 18.5–2; an increased risk was observed for a BMI ≥30 kg/m2, although there was little difference comparing women with endometriosis (OR = 1.21; 95% CI, 0.94–1.57) to women without (OR = 1.13; 95% CI, 1.04–1.22) (P-interaction = .51). Genital talcum powder use and long-term menopausal estrogen-only therapy use showed increased ovarian cancer risk, but risk appeared greater for those with endometriosis vs. those without (genital talcum powder: OR = 1.38; 95% CI, 1.04–1.84 vs. OR = 1.12; 95% CI, 1.01–1.25, respectively; ≥10 years of estrogen-only therapy: OR = 1.88; 95% CI, 1.09–3.24 vs. OR = 1.42; 95% CI, 1.14–1.76, respectively); neither of these interactions were statistically significant (P-interaction = .65 and P-interaction = .96, respectively). Conclusion(s): The associations between ovarian cancer and most risk factors were similar among women with and without endometriosis. However, there was some suggestion of differences by endometriosis status for BMI, menopausal hormone therapy use, and genital talcum powder use, highlighting the complexity of ovarian cancer etiology.

Introduction Malignant pleural effusions (MPEs) are common. MPE causes significant breathlessness and impairs quality of life. Indwelling pleural catheters (IPC) allow ambulatory drainage and reduce hospital days and re-intervention rates when compared to standard talc slurry pleurodesis. Daily drainage accelerates pleurodesis, and talc instillation via the IPC has been proven feasible and safe. Surgical pleurodesis via video-assisted thoracoscopic surgery (VATS) is considered a one-off intervention for MPE and is often recommended to patients who are fit for surgery. The AMPLE-3 trial is the first randomised trial to compare IPC (±talc pleurodesis) and VATS pleurodesis in those who are fit for surgery. Methods and analysis A multi-centre, open-labelled randomised trial of patients with symptomatic MPE, expected survival of ≥ 6 months and good performance status randomised 1:1 to either IPC or VATS pleurodesis. Participant randomisation will be minimised for (i) cancer type (mesothelioma vs non-mesothelioma); (ii) previous pleurodesis (vs not); and (iii) trapped lung, if known (vs not). Primary outcome is the need for further ipsilateral pleural interventions over 12 months or until death, if sooner. Secondary outcomes include days in hospital, quality of life (QoL) measures, physical activity levels, safety profile, health economics, adverse events, and survival. The trial will recruit 158 participants who will be followed up for 12 months. Ethics and dissemination Sir Charles Gairdner and Osborne Park Health Care Group (HREC) has approved the study (reference: RGS356). Results will be published in peer-reviewed journals and presented at scientific meetings. Discussion Both IPC and VATS are commonly used procedures for MPE. The AMPLE-3 trial will provide data to help define the merits and shortcomings of these procedures and inform future clinical care algorithms. Trial registration Australia New Zealand Clinical Trial Registry ACTRN12618001013257. Registered on 18 June 2018. Protocol version: Version 3.00/4.02.19

The first NHLBI Clinical Trials Research Network was the Asthma Clinical Research Network (ACRN 1), which was born in 1993 to perform multiple controlled clinical trials for asthma: “… dispassionately examine new & existing therapies for asthma” and “… rapidly communicate findings to medical community,” and therefore, to perform clinical trials drug companies could not or would not do. Among the many areas studied by the ACRN and its successor networks, through 2019, was how to effectively and safely use long-acting beta-agonists and to find novel alternatives for them. In its Tiotropium Add-On Trial (TALC) trial, the ACRN demonstrated that tiotropium as add on-therapy to inhaled corticosteroids (ICS) was effective and non-inferior to long-acting beta-agonist add on-therapy. During the lifetime of the clinical trial networks (1993–2020), 71 manuscripts including 25 major clinical trials were published, many which have laid the groundwork for precision approaches for asthma therapy and the now ongoing PrecISE Asthma Network.

Objective To update the analysis of mortality of a cohort of talc miners and millers in Northern Italy. Methods We analyzed overall mortality and mortality from specific causes of death during 1946–2020 of 1749 male workers in a talc mine where asbestos was not detected (1184 miners and 565 millers) employed during 1946–1995. Results The overall standardized mortality ratio (SMR) was 1.21 (95 % confidence interval [CI] 1.14–1.28); no deaths were observed from pleural cancer. Mortality from lung cancer was not increased (SMR = 1.02 95 % CI 0.82–1.27), while mortality from pneumoconiosis was (SMR 9.55; 95 % CI 7.43–12.08), especially among miners (SMR 12.74; 95 % CI 9.79–16.31). There was a trend in risk of pneumoconiosis with increasing duration of employment in the overall cohort, and the SMR for 25+ years of employment was 15.12 (95 % CI 10.89–20.43). Conclusions This uniquely long-term follow up confirms the results of previous analyses, namely the lack of association between exposure to talc with no detectable level of asbestos and lung cancer and mesothelioma. Increased mortality from pneumoconiosis among miners is related to past exposure to silica.

Background: Black women are at an increased risk of developing fibroids, but the cause is unclear. Douching and perineal talc use are common lifestyle exposures among Black women, and may be risk factors for fibroid development. Materials and Methods: This cross-sectional study consisted of Black women 23–35 years of age in the metropolitan Detroit area (n = 1693) without prior diagnoses of fibroids and intact uteri. Main exposures were ever douching (yes/no) and any perineal talc use (ever/never). Main outcomes were prevalent fibroids at baseline (yes/no) and total fibroid volume at baseline (no fibroids/

Malignant pleural effusions have a significant burden on patients and the health care system. Diagnosis is typically via thoracentesis, although other times more invasive procedures are required. Management centers around relief of dyspnea and patient quality of life and can be done via serial thoracentesis, indwelling pleural catheter, or pleurodesis. This article focuses on the diagnosis and management of malignant pleural effusion.

Following cervical and uterine cancer, ovarian cancer (OC) has the third rank in gynecologic cancers. It often remains non-diagnosed until it spreads throughout the pelvis and abdomen. Identification of the most effective risk factors can help take prevention measures concerning OC. Therefore, the presented review aims to summarize the available studies on OC risk factors. A comprehensive systematic literature search was performed to identify all published systematic reviews and meta-analysis on associated factors with ovarian cancer. Web of Science, Cochrane Library databases, and Google Scholar were searched up to 17th January 2020. This study was performed according to Smith et al. methodology for conducting a systematic review of systematic reviews. Twenty-eight thousand sixty-two papers were initially retrieved from the electronic databases, among which 20,104 studies were screened. Two hundred seventy-seven articles met our inclusion criteria, 226 of which included in the meta-analysis. Most commonly reported genetic factors were MTHFR C677T (OR=1.077; 95 % CI (1.032, 1.124); P-value

International audience; Inorganic antigens may contribute to paediatric sarcoidosis. Thirty-six patients matched with 36 healthy controls as well as a group of 21 sickle-cell disease (SCD) controls answered an environmental questionnaire. Patients' indirect exposure to inorganic particles, through coresidents' occupations, was higher than in healthy and SCD controls (median score: 2.5 (0.5-7) vs 0.5 (0-2), p=0.003 and 1 (0-2), p=0.012, respectively), especially for construction, exposures to metal dust, talc, abrasive reagents and scouring products. Wood or fossil energies heating were also linked to paediatric sarcoidosis. This study supports a link between mineral environmental exposure due to adult coresident occupations and paediatric sarcoidosis.

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Background and Aim: Talc poudrage has been used since many years for sclerosing chronic pleural effusion. Several reports have shown good results managing chronic seromas after breast, vascular, and incisional hernia surgeries. The purpose of this study is to determine the utility of talc seromadesis for the management of chronic seromas after incisional hernia surgery Materials and Methods: Multicentric prospective observational study including patients diagnosed of chronic seromas after incisional hernia surgery. Under local anesthesia and ultrasonographic control, two percutaneous trocars were placed in the seroma, washing the seroma cavity with 0.9% saline solution and aspirating the remaining liquid. A sample of 4 g of talcum powder was introduced in the seroma cavity, and a 15-F drain was left in place. Patients were followed each week during at least 4 weeks after drainage removal. Results: Between January 2013 and December 2016, a total of six patients were enrolled in the study. Talc poudrage was performed without any complications. Drains were pulled out in a mean time of 3 (range: 2–4) weeks. One case of the chronic seromas was efficiently sclerosed with talc without recurrence in time. In three cases, the seroma recurred, and the final solution was surgical decortication of the seroma. In the other two cases, seroma also recurred and were managed with instillation of ethanol and iodine povidone. Conclusion: In our experience, the management of chronic seromas after incisional hernia repair with talc seromadesis is ineffective and is associated with a high rate of seroma recurrence.

Genital use of talcum powder and its associated risk of ovarian cancer is an important controversial topic. Epithelial ovarian cancer (EOC) cells are known to manifest a persistent prooxidant state. Here we demonstrated that talc induces significant changes in key redox enzymes and enhances the prooxidant state in normal and EOC cells. Using real-time reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay, levels of CA-125, caspase-3, nitrate/nitrite, and selected key redox enzymes, including myeloperoxidase (MPO), inducible nitric oxide synthase (iNOS), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), and glutathione reductase (GSR), were determined. TaqMan genotype analysis utilizing the QuantStudio 12K Flex was used to assess single-nucleotide polymorphisms in genes corresponding to target enzymes. Cell proliferation was determined by MTT proliferation assay. In all talc-treated cells, there was a significant dose-dependent increase in prooxidant iNOS, nitrate/nitrite, and MPO with a concomitant decrease in antioxidants CAT, SOD, GSR, and GPX (P < .05). Remarkably, talc exposure induced specific point mutations that are known to alter the activity in some of these key enzymes. Talc exposure also resulted in a significant increase in inflammation as determined by increased tumor marker CA-125 (P < .05). More importantly, talc exposure significantly induced cell proliferation and decreased apoptosis in cancer cells and to a greater degree in normal cells (P < .05). These findings are the first to confirm the cellular effect of talc and provide a molecular mechanism to previous reports linking genital use to increased ovarian cancer risk.

Objectives Recent observations indicate a potential survival benefit in patients with malignant pleural effusion (MPE) who achieve successful pleurodesis in comparison to patients who experience effusion recurrence post pleurodesis. This study aimed to explore this observation using two datasets of patients with MPE undergoing talc pleurodesis. Materials and Methods Dataset 1 comprised patients who underwent talc pleurodesis at Oxford Pleural Unit for MPE. Dataset 2 comprised patients enrolled in the TIME1 clinical trial. Pleurodesis success was defined as absence of need for further therapeutic procedures for MPE in the three months following pleurodesis. Data on various clinical, laboratory and radiological parameters were collected and survival was compared according to pleurodesis outcome (success vs. failure) after adjusting for the aforementioned parameters. Results Dataset 1 comprised 60 patients with mean age 74.1±10.3 years. The most common primary malignancies were mesothelioma, breast and lung cancer. 29 patients (48.3%) achieved pleurodesis. The adjusted odds ratio (aOR) for poor survival with pleurodesis failure was 2.85 (95% CI 1.08–7.50, =p 0.034). Dataset 2 comprised 259 patients from the TIME1 trial. The mean age was 70.8±10.3 and the most common primary malignancies were mesothelioma, lung and breast cancer. Pleurodesis was successful in 205 patients (79%). aOR for poor survival was 1.62 (95% CI 1.09–2.39, p = 0.015). Conclusion Achieving pleurodesis seems to impart a survival benefit in patients with MPE. Further studies are required to explore factors that may contribute to this phenomenon and to address the difference in survival between pleurodesis and indwelling pleural catheter interventions.

Background: Douching is associated with disorders involving genital tract inflammation and genital talc use with epithelial ovarian cancer (EOC), but their joint effects are infrequently considered. Methods: From 2,040 cases of EOC and 2,100 controls enrolled in eastern Massachusetts and New Hampshire, we used unconditional logistic regression to estimate risk for EOC associated with douching and/or talc use. In subsets of cases and controls, we also collected information about pelvic inflammatory disease (PID), ectopic pregnancy, and cervical neoplasia to estimate risk for these events from douching and/or talc use. Results: The adjusted OR and 95% confidence interval (CI) for all EOC was 0.94 (0.76–1.16) in women who douched but never used talc and 1.28 (1.09–1.51) in women who used talc but never douched. Compared with women who never regularly douched or used talc, ORs (95% CIs) were 0.83 (0.52–1.33) for women who both used talc and homemade douches and 1.53 (1.11–2.10) for women who both used talc and store-bought douches. Cases who both douched and used talc were more likely to have had PID compared with cases who had used neither [OR = 5.03 (95% CI, 1.61–15.7)]. Conclusions: Douching is not an independent risk factor for ovarian cancer, but the combination of talc use and store-bought douches may modestly increase the risk for EOC beyond that for talc use alone. Impact: The joint effect of talc use and douching, especially with commercial products, should be considered in evaluating risks associated with disorders involving genital tract inflammation or EOC.

The aim of this study was to update a cohort of Vermont talc workers to include 37 additional years of follow-up time.Standardized mortality ratios (SMR) and 95% confidence intervals (CIs) were calculated for 70+ causes of death. US population mortality rates were used as reference.All-cause mortality was 30% higher than the US population (SMR 133.4, 95% CI, 119.7 to 148.3). Significant elevations occurred in nonmalignant respiratory disease (NMRD) (SMR 273.0, 95% CI, 210.2 to 348.6) and other nonmalignant respiratory disease (ONMRD) (SMR 413.1, 95% CI, 287.7 to 574.5). ONMRD was elevated across all length of employment categories and a test for linear trend was significant (P = 0.007).This study provides further evidence that excess deaths among Vermont talc workers are due largely to excess mortality from NMRD; there is no evidence of increased risk of respiratory cancer.

Background Perineal talc use and douching could affect the risk of uterine cancer through several possible pathways, including inflammation response, microbiota changes, or endocrine disruption. Two previous cohort studies of the association between talc use and uterine cancer have reported weak positive associations, but we know of no previous evaluations of the relationship between douching and uterine cancer. Methods Using a large prospective cohort, we examined the relationship between incident uterine cancer and self-reported use of talc or douche using Cox proportional hazards models. Results After excluding those with prior hysterectomy, 271 of 33,609 women reported incident uterine cancer (mean follow-up = 8.3 years in noncases; maximum 12.6 years). Overall, 26% of women reported ever using talc and 15% reported ever having douched. Ever talc use was associated with an increase in risk of uterine cancer (adjusted hazard ratio [HR] = 1.2; 95% confidence interval [CI] = 0.94, 1.6), with some evidence of a dose-response for frequency of talc use (P-for-trend = 0.07). Ever douching was not associated with uterine cancer risk (HR = 1.0; 95% CI = 0.72, 1.5), with no evidence of a frequency dose-response (P = 0.96). The estimates were similar when we restricted to invasive endometrial cancers, but not when we further restricted to endometroid adenocarcinomas. Conclusion The positive association we observed between talc use and uterine cancer risk is consistent with findings from previous prospective cohort studies of endometrial cancer. The relationships between uterine cancer and both douching and talc use merit further consideration, particularly as both exposures are preventable.

Sir,We have reviewed the letters submitted by Finkelstein (2019) and Madigan et al. (2019) regarding our updated pooled analysis of mesothelioma risk following occupational exposures to cosmetic ta...

Talc remains a common sclerosant utilized for pleurodesis. However, the use of talc has documented complications and debate has persisted regarding the safety of talc as well as the differences in talc preparations available throughout the world. We sought to describe an up-to-date review of talc preparations available and the impact these preparations may have on the safety profile of talc.Within laboratory-based examinations, talc particle size available within the United States appears to be more consistent with prior reported 'safe' particle sizes. The presence of talc within protein-based solutions appears to modify the overall milieu of the solution and likely results in particle aggregation.The use of talc remains well accepted for pleurodesis as evidenced by inclusion by multiple guidelines. The medical fields' current understanding of talc and its basic interactions within the pleural space remain limited. Multiple questions related to the pleural space and pleurodesis remain unanswered.

BackgroundMalignant pleural effusion (MPE) results in breathlessness and impairment of health-related quality of life (HRQOL). This study reviews the existing literature on HRQOL following invasive interventions in MPE.MethodsFive electronic databases were systematically searched and assessed three times during the review process and last completed on 15 June 2018. We included all studies evaluating HRQOL outcomes for the following interventions: therapeutic thoracocentesis, talc slurry (TS) pleurodesis, indwelling pleural catheter (IPC) insertion and thoracoscopic talc poudrage (TTP) pleurodesis. Meta-analysis was not performed due to substantial heterogeneity in the published data.Results17 studies were included in the review reporting HRQOL outcomes in 2515 patients. TTP, TS and IPC were associated with modest but inconsistent improvements in HRQOL up to 12 weeks. No intervention was significantly different from another in HRQOL outcomes at any time point. The attrition to follow-up was 48.3% (664/1374) at 3 months. The overall quality of studies was inadequate.ConclusionTTP, TS and IPC seem to improve HRQOL in MPE over 4–12 weeks, but there are insufficient longer term data due to high attrition rates. Evidence on the most effective treatment strategy is limited by the small number of randomised or comparative studies.Trial registration numberCRD42016051003.

Symptomatic pleural disease, specifically malignant pleural effusion, refractory benign pleural effusion, and pneumothoraces are common diseases that often require therapeutic interventions. The spectrum of management strategies often includes selection of a chemical pleurodesis agent administered in combination with an indwelling pleural catheter or chest tube.Additionally, there is a role for minimally invasive techniques which include medical thoracoscopy or more advanced video-assisted thoracoscopic approaches. Ongoing clinical trials continue to evolve best practices regarding the optimal sclerosant agents and procedural approaches in the management of these diseases.

Objectives: We previously published a pooled statistical power analysis of mesothelioma incidence in the Italian, Norwegian, Austrian, and French cosmetic talc miner and miller cohorts. Soon thereafter, updates to the Italian and Norwegian cohorts were published, providing an additional 14,322 person-years of observation. In this study, we provide an updated power analysis using the newly available information. Methods: We pooled the current results regarding pleural cancer/mesothelioma mortality or incidence in four cosmetic talc miner and miller cohorts in Italy, Norway, Austria, and France. We used the expected numbers of cases as reported by the authors and the power analysis was based on an a priori one-sided significance level of 0.05 and Poisson distribution probabilities. Results: There was a pooled total of 113,344 person-years in the cohorts. Although 3.0 pleural cancers/mesotheliomas were expected, there were no reported pleural cancer or mesothelioma cases in any cohort. Our pooled analysis was associated with 79 and 62% power to detect a 3.0-fold and 2.5-fold or greater increase in pleural cancer/mesothelioma, respectively. These favorable power characteristics were effectively maintained when restricting the pooled cohort to workers with a latency period of 30 or more years (observation time from first employment). Conclusions: The epidemiological evidence from the cosmetic talc miner/miller cohort studies does not support the hypothesis that exposure to cosmetic talc is associated with the development of pleural cancer/mesothelioma.

Background Yellow nail syndrome is a rare disease with unknown etiology, Attributed to functional anomalies or disturbance in lymphatic drainage. This condition is characterized by triad of nail discoloration, respiratory or intrathoracic manifestations and lymphedema. Case presentation Twenty days after mitral valve replacement for severe rheumatic mitral valve stenosis, 39 years old woman presented with face tenderness and hearing problems besides stuffy and clogged nose and underwent routin rhinosinusitis therapy. She came back to ears, nose and throat service with persistent rhinosinusitis as well as relapsing preoperative couphs and dyspnea besides lower extremities edema and toenails discoloration. After some modulations of treatment, she was introduced to pulmonary clinic on post -operative day = 30. Chest x ray showed a lot of left pleural effusion then she was returned to our service (cardiac surgery) on post- operative day = 33. The pigtail catheter was secured and we attained a significant amount of milky fluid which conformed with chylothorax. Finally Yellow nail syndrome was diagnosed with her on post–operative day = 35. Early conservative therapy such as bed rest, legs massage, low fat diet with medium chain triglycerides, diuretics, bronchodilator inhaler was not be able to satisfy us (chylous out put > 330 cc/d). Therefore the catheter replacement with chest tube was carried out followed by pleurodesis using Talc and doxycycline besides transition of oral intake to total parentral nutrition and vitamine E supplement, on post - operative day = 41. After that chylous leakage gradually subsided and patient was discharged to home on post- operative day = 47. At 4 weeks follow ups, chest x ray was clear without effusion and nails discoloration and legs lymphedema resolved. Conclusion We reported the third post cardiac surgery Yellow nail syndrome which is an unclear entity with a set of associated signs and symptoms. Two prior reports involved with coronary artery bypass graft whereas we performed mitral valve replacement. In angiogram thoracic duct was not identified so that it seems post cardiac surgery Yellow nail the syndrome has iatrogenic origin due to the thoracic duct or its tributaries injury and requires meticulous assessment and management.

The pathophysiology and management of primary spontaneous pneumothorax (PSP) are a subject of debate. Despite advances in the understanding of its etiopathogenesis and improvements in its management, implementation in clinical practice is suboptimal. In this manuscript, we review the recent literature with a focus on PSP pathophysiology and management. Blebs and emphysema-like changes (ELC) are thought to contribute to the pathophysiology of PSP but cannot explain all cases. Recent studies emphasize the role of a diffuse porosity of the visceral pleura. Others found a relationship between smoking, occurrence of a PSP and bronchiolitis, which could be the initial pathological process leading to ELC development. Recent or ongoing studies challenge the need to systematically remove air from the pleural cavity of stable patients, introducing conservative management as a valuable therapeutic option. Evidence is growing in favour of needle aspiration instead of chest tube insertion, when air evacuation is needed. In addition, ambulatory management is considered as a successful approach in meta-analyses and is under exploration in a large randomized study. Because of a high recurrence rate of PSP, the benefit of performing a pleurodesis at first occurrence is under evaluation with interesting but not generalizable results. Better identification of 'at risk patients' is needed to improve the investigation strategy. Finally, recent publications confirm the efficacy, security and cost-effectiveness of graded talc poudrage pleurodesis to prevent PSP recurrence. In conclusion, PSP pathophysiology and management are still under investigation. The results of recently published and ongoing studies should be more widely implemented in clinical practice.

Perineal talc use is associated with ovarian carcinoma in many case-control studies. Such talc may migrate to pelvic organs and regional lymph nodes, with both clinical and legal significance. Our goal was to differentiate talc in pelvic lymph nodes due to exposure, versus contamination with talc in the laboratory. We studied 22 lymph nodes from ovarian tumor patients, some of which had documented talc exposure, to quantify talc using digestion of tissue taken from paraffin blocks and scanning electron microscopy/energy dispersive X-ray analysis (SEM/EDX). Talc particles correlated significantly with surface contamination assessments using polarized light microscopy. After adjusting for surface contamination, talc burdens in nodes correlated strongly with perineal talc use. In a separate group of lymph nodes, birefringent particles within the same plane of focus as the tissues in histological sections were highly correlated with talc particles within the tissue by in situ SEM/EDX (r = 0.80; p < 0.0001). We conclude that since talc can be a surface contaminant from tissue collection/preparation, digestion measurements may be influenced by contamination. Instead, because they preserve anatomic landmarks and permit identification of particles in cells and tissues, polarized light microscopy and in situ SEM/EDX are recommended to assess talc in lymph nodes.