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The European Respiratory Journal Jun 2020The European Respiratory Society (ERS)/European Society of Thoracic Surgeons (ESTS)/European Association for Cardio-Thoracic Surgery (EACTS)/European Society for...
The European Respiratory Society (ERS)/European Society of Thoracic Surgeons (ESTS)/European Association for Cardio-Thoracic Surgery (EACTS)/European Society for Radiotherapy and Oncology (ESTRO) task force brought together experts to update previous 2009 ERS/ESTS guidelines on management of malignant pleural mesothelioma (MPM), a rare cancer with globally poor outcome, after a systematic review of the 2009-2018 literature. The evidence was appraised using the Grading of Recommendations, Assessment, Development and Evaluation approach. The evidence syntheses were discussed and recommendations formulated by this multidisciplinary group of experts. Diagnosis: pleural biopsies remain the gold standard to confirm the diagnosis, usually obtained by thoracoscopy but occasionally image-guided percutaneous needle biopsy in cases of pleural symphysis or poor performance status. Pathology: standard staining procedures are insufficient in ∼10% of cases, justifying the use of specific markers, including and () for the separation of atypical mesothelial proliferation from MPM. Staging: in the absence of a uniform, robust and validated staging system, we advise using the most recent 2016 8th TNM (tumour, node, metastasis) classification, with an algorithm for pre-therapeutic assessment. Monitoring: patient's performance status, histological subtype and tumour volume are the main prognostic factors of clinical importance in routine MPM management. Other potential parameters should be recorded at baseline and reported in clinical trials. Treatment: (chemo)therapy has limited efficacy in MPM patients and only selected patients are candidates for radical surgery. New promising targeted therapies, immunotherapies and strategies have been reviewed. Because of limited data on the best combination treatment, we emphasise that patients who are considered candidates for a multimodal approach, including radical surgery, should be treated as part of clinical trials in MPM-dedicated centres.
Topics: Humans; Medical Oncology; Mesothelioma; Mesothelioma, Malignant; Pleural Neoplasms; Surgeons
PubMed: 32451346
DOI: 10.1183/13993003.00953-2019 -
The Cochrane Database of Systematic... Apr 2020Malignant pleural effusion (MPE) is a common problem for people with cancer and usually associated with considerable breathlessness. A number of treatment options are... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Malignant pleural effusion (MPE) is a common problem for people with cancer and usually associated with considerable breathlessness. A number of treatment options are available to manage the uncontrolled accumulation of pleural fluid, including administration of a pleurodesis agent (via a chest tube or thoracoscopy) or placement of an indwelling pleural catheter (IPC). This is an update of a review published in Issue 5, 2016, which replaced the original, published in 2004.
OBJECTIVES
To ascertain the optimal management strategy for adults with malignant pleural effusion in terms of pleurodesis success and to quantify differences in patient-reported outcomes and adverse effects between interventions.
SEARCH METHODS
We searched CENTRAL, MEDLINE (Ovid), Embase (Ovid) and three other databases to June 2019. We screened reference lists from other relevant publications and searched trial registries.
SELECTION CRITERIA
We included randomised controlled trials of intrapleural interventions for adults with symptomatic MPE, comparing types of sclerosant, mode of administration and IPC use.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data on study design, characteristics, outcome measures, potential effect modifiers and risk of bias. The primary outcome was pleurodesis failure rate. Secondary outcomes were adverse events, patient-reported breathlessness control, quality of life, cost, mortality, survival, duration of inpatient stay and patient acceptability. We performed network meta-analyses of primary outcome data and secondary outcomes with enough data. We also performed pair-wise meta-analyses of direct comparison data. If we deemed interventions not jointly randomisable, or we found insufficient available data, we reported results by narrative synthesis. For the primary outcome, we performed sensitivity analyses to explore potential causes of heterogeneity and to evaluate pleurodesis agents administered via a chest tube only. We assessed the certainty of the evidence using GRADE.
MAIN RESULTS
We identified 80 randomised trials (18 new), including 5507 participants. We found all except three studies at high or unclear risk of bias for at least one domain. Due to the nature of the interventions, most studies were unblinded. Pleurodesis failure rate We included 55 studies of 21 interventions in the primary network meta-analysis. We estimated the rank of each intervention's effectiveness. Talc slurry (ranked 6, 95% credible interval (Cr-I) 3 to 10) is an effective pleurodesis agent (moderate certainty for comparison with placebo) and may result in fewer pleurodesis failures than bleomycin and doxycycline (bleomycin versus talc slurry: odds ratio (OR) 2.24, 95% Cr-I 1.10 to 4.68; low certainty; ranked 11, 95% Cr-I 7 to 15; doxycycline versus talc slurry: OR 2.51, 95% Cr-I 0.81 to 8.40; low certainty; ranked 12, 95% Cr-I 5 to 18). There is little evidence of a difference between the pleurodesis failure rate of talc poudrage and talc slurry (OR 0.50, 95% Cr-I 0.21 to 1.02; moderate certainty). Evidence for any difference was further reduced when restricting analysis to studies at low risk of bias (defined as maximum one high risk domain in the risk of bias assessment) (pleurodesis failure talc poudrage versus talc slurry: OR 0.78, 95% Cr-I 0.16 to 2.08). IPCs without daily drainage are probably less effective at obtaining a definitive pleurodesis (cessation of pleural fluid drainage facilitating IPC removal) than talc slurry (OR 7.60, 95% Cr-I 2.96 to 20.47; rank = 18/21, 95% Cr-I 13 to 21; moderate certainty). Daily IPC drainage or instillation of talc slurry via IPC are likely to reduce pleurodesis failure rates. Adverse effects Adverse effects were inconsistently reported. We performed network meta-analyses for the risk of procedure-related fever and pain. The evidence for risk of developing fever was of low certainty, but suggested there may be little difference between interventions relative to talc slurry (talc poudrage: OR 0.89, 95% Cr-I 0.11 to 6.67; bleomycin: OR 2.33, 95% Cr-I 0.45 to 12.50; IPCs: OR 0.41, 95% Cr-I 0.00 to 50.00; doxycycline: OR 0.85, 95% Cr-I 0.05 to 14.29). Evidence also suggested there may be little difference between interventions in the risk of developing procedure-related pain, relative to talc slurry (talc poudrage: OR 1.26, 95% Cr-I 0.45 to 6.04; very-low certainty; bleomycin: OR 2.85, 95% Cr-I 0.78 to 11.53; low certainty; IPCs: OR 1.30, 95% Cr-I 0.29 to 5.87; low certainty; doxycycline: OR 3.35, 95% Cr-I 0.64 to 19.72; low certainty). Patient-reported control of breathlessness Pair-wise meta-analysis suggests there is likely no difference in breathlessness control, relative to talc slurry, of talc poudrage ((mean difference (MD) 4.00 mm, 95% CI -6.26 to 14.26) on a 100 mm visual analogue scale for breathlessness; studies = 1; participants = 184; moderate certainty) and IPCs without daily drainage (MD -6.12 mm, 95% CI -16.32 to 4.08; studies = 2; participants = 160; low certainty). Overall mortality There may be little difference between interventions when compared to talc slurry (bleomycin and IPC without daily drainage; low certainty) but evidence is uncertain for talc poudrage and doxycycline. Patient acceptability Pair-wise meta-analysis demonstrated that IPCs probably result in a reduced risk of requiring a repeat invasive pleural intervention (OR 0.25, 95% Cr-I 0.13 to 0.48; moderate certainty) relative to talc slurry. There is likely little difference in the risk of repeat invasive pleural intervention with talc poudrage relative to talc slurry (OR 0.96, 95% CI 0.59 to 1.56; moderate certainty).
AUTHORS' CONCLUSIONS
Based on the available evidence, talc poudrage and talc slurry are effective methods for achieving a pleurodesis, with lower failure rates than a number of other commonly used interventions. IPCs provide an alternative approach; whilst associated with inferior definitive pleurodesis rates, comparable control of breathlessness can probably be achieved, with a lower risk of requiring repeat invasive pleural intervention. Local availability, global experience of agents and adverse events (which may not be identified in randomised trials) and patient preference must be considered when selecting an intervention. Further research is required to delineate the roles of different treatments according to patient characteristics, such as presence of trapped lung. Greater attention to patient-centred outcomes, including breathlessness, quality of life and patient preference is essential to inform clinical decision-making. Careful consideration to minimise the risk of bias and standardise outcome measures is essential for future trial design.
Topics: Adult; Bleomycin; Doxycycline; Dyspnea; Fever; Humans; Iodine; Network Meta-Analysis; Pleural Effusion, Malignant; Pleurodesis; Quinacrine; Randomized Controlled Trials as Topic; Talc; Treatment Failure
PubMed: 32315458
DOI: 10.1002/14651858.CD010529.pub3 -
Clinical and Translational Science Jun 2022The exact role of pleural effusion in the prognosis of cancer patients remains unclear. We aimed to systematically review the prognostic value of pleural effusion in... (Meta-Analysis)
Meta-Analysis Review
The exact role of pleural effusion in the prognosis of cancer patients remains unclear. We aimed to systematically review the prognostic value of pleural effusion in patients with cancer. We performed a systematic review and meta-analysis with a systematic literature search. All cohort studies with available overall survival (OS) and progression-free survival (PFS) results for patients with cancer with or without pleural effusion were included. The Mantel-Haenszel method was used to calculate the pooled hazard ratios (HRs) and 95% confidence intervals (CIs). Heterogeneity and publication bias were examined. Subgroup analysis and sensitivity analysis were performed. A total of 47 studies with 146,117 patients were included in the analysis. For OS, pleural effusion was a prognostic factor associated with a poor prognosis for patients with cancer (HR, 1.58, 95% CI, 1.43-1.75; I 94.8%). In the subgroup analysis, pleural effusion was a prognostic factor associated with poor survival for patients with lung cancer (HR, 1.44, 95% CI, 1.35-1.54; I 60.8%), hematological cancer (HR, 2.79, 95% CI, 1.63-4.77; I 29.4%) and other types of cancer (HR, 2.08, 95% CI, 1.43-3.01; I 55.1%). For PFS, pleural effusion was a prognostic factor associated with a poor prognosis for patients with cancer (HR, 1.61, 95% CI, 1.28-2.03; I 42.9%). We also observed that massive pleural effusion was a prognostic factor associated with a poorer prognosis compared to minimal pleural effusion. Pleural effusion had prognostic value in both OS and PFS of patients with cancer, except for patients with malignant pleural mesothelioma, regardless of whether the malignant effusion was confirmed histologically or cytologically. However, future evidence of other pleural effusion characteristics is still needed.
Topics: Humans; Lung Neoplasms; Mesothelioma, Malignant; Pleural Effusion; Prognosis; Proportional Hazards Models
PubMed: 35212454
DOI: 10.1111/cts.13260 -
Thorax Jan 2023Pleural fluid cytology is an important diagnostic test used for the investigation of pleural effusions. There is considerable variability in the reported sensitivity for... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Pleural fluid cytology is an important diagnostic test used for the investigation of pleural effusions. There is considerable variability in the reported sensitivity for the diagnosis of malignant pleural effusions (MPE) in the literature.
OBJECTIVE
The purpose of this review is to determine the diagnostic sensitivity of pleural fluid cytology for MPE, both overall and by tumour type, to better inform the decision-making process when investigating pleural effusions.
DATA SOURCES
A literature search of EMBASE and MEDLINE was performed by four reviewers. Articles satisfying inclusion criteria were evaluated for bias using the QUADAS-2 tool.
DATA EXTRACTION
For quantitative analysis, we performed a metaanalysis using a binary random-effects model to determine pooled sensitivity. Subgroup analysis was performed based on primary cancer site and meta-regression by year of publication.
SYNTHESIS
Thirty-six studies with 6057 patients with MPE were included in the meta-analysis. The overall diagnostic sensitivity of pleural fluid cytology for MPE was 58.2% (95% CI 52.5% to 63.9%; range 20.5%-86.0%). There was substantial heterogeneity present among studies (I 95.5%). For primary thoracic malignancies, sensitivity was highest in lung adenocarcinoma (83.6%; 95% CI 77.7% to 89.6%) and lowest in lung squamous cell carcinoma (24.2%; 95% CI 17.0% to 31.5%) and mesothelioma (28.9%; 95% CI 16.2% to 41.5%). For malignancies with extrathoracic origin, sensitivity was high for ovarian cancer (85.2%; 95% CI 74.2% to 96.1%) and modest for breast cancer (65.3%; 95% CI 49.8% to 80.8%).
CONCLUSIONS
Pleural fluid cytology has an overall sensitivity of 58.2% for the diagnosis of MPE. Clinicians should be aware of the high variability in diagnostic sensitivity by primary tumour type as well as the potential reasons for false-negative cytology results.PROSPERO registration numberCRD42021231473.
Topics: Humans; Pleural Effusion, Malignant; Pleura; Mesothelioma; Pleural Effusion; Lung Neoplasms; Sensitivity and Specificity
PubMed: 35110369
DOI: 10.1136/thoraxjnl-2021-217959 -
Expert Review of Respiratory Medicine Jan 2020: Malignant pleural mesothelioma (MPM) is a fatal malignancy for which there is no definitive cure. The most effective multimodality treatment in prolonging survival is...
: Malignant pleural mesothelioma (MPM) is a fatal malignancy for which there is no definitive cure. The most effective multimodality treatment in prolonging survival is still matter of debate. Surgery remains one of the cornerstones in the multimodality therapy for MPM. Extra-pleural pneumonectomy and pleurectomy/decortication are the two main curative-intent procedures; however, the superiority of one technique over the other is still debated. This review aims to assess short- and long-term results of extrapleural pneumonectomy for MPM.: This article focuses on the role of extrapleural pneumonectomy in MPM. A systematic review was performed by using electronic databases to identify studies that included patients treated by this procedure for MPM. Endpoints included overall survival, disease-free survival, recurrence rate, perioperative mortality, and morbidity.: This paper offers an overview of the results that are currently obtained in patients undergoing extrapleural pneumonectomy for MPM. The benefit of surgical treatments in MPM is still debated and its primary goal should be the achievement of a macroscopic complete resection. Several alternative multimodality protocols exist, with specific advantages and drawbacks; therefore, individualization of care for each patient is fundamental. The complexity of the surgical treatment mandates that patients be referred to specialized centers.
Topics: Humans; Mesothelioma; Mesothelioma, Malignant; Pleural Neoplasms; Pneumonectomy; Treatment Outcome
PubMed: 31674841
DOI: 10.1080/17476348.2020.1688147 -
Cancer Dec 2023Obesity has been recognized as a risk factor in the development and recurrence of breast cancer and is also associated with poor prognostic outcomes. This systematic... (Meta-Analysis)
Meta-Analysis Review
What are the most effective exercise, physical activity and dietary interventions to improve body composition in women diagnosed with or at high-risk of breast cancer? A systematic review and network meta-analysis.
BACKGROUND
Obesity has been recognized as a risk factor in the development and recurrence of breast cancer and is also associated with poor prognostic outcomes. This systematic review and network meta-analysis aimed to identify the most effective exercise, physical activity, and dietary interventions to reduce fat mass, body fat percentage and body weight as well as potentially increase lean mass in women diagnosed with or at high risk of breast cancer.
METHODS
A systematic search of databases was performed up to May 2022. Eligible randomized controlled trials examined the effects of exercise, physical activity and/or dietary interventions on fat mass and lean mass in women diagnosed with or at high risk of breast cancer. A random-effects network meta-analysis was conducted to determine the effects of different interventions across outcomes when sufficient studies were available.
RESULTS
Eighty-four studies (n = 6428) were included in this review. Caloric restriction and combined exercise + caloric restriction significantly reduced fat mass (range, -3.9 to -3.7 kg) and body weight (range, -5.3 to -4.7 kg), whereas physical activity + caloric restriction significantly reduced body fat percentage (-2.4%; 95% confidence interval [CI], -3.4% to -13%) and body mass index (-2.2 kg × m ; 95% CI, -3.0 to -1.4 kg × m ) in breast cancer patients. Resistance exercise was the most effective intervention to increase lean mass (0.7 kg; 95% CI, 0.5-1.0 kg) in breast cancer patients.
CONCLUSION
Multimodal exercise and diet programs were the most effective interventions to reduce fat mass, body fat percentage, and body weight and increase and/or preserve lean mass.
Topics: Humans; Female; Breast Neoplasms; Network Meta-Analysis; Body Weight; Exercise; Body Composition
PubMed: 37788151
DOI: 10.1002/cncr.35043 -
European Respiratory Review : An... Dec 2022Thoracentesis and thoracoscopy are used to diagnose malignant pleural effusions (MPE). Data on how sensitivity varies with tumour type is limited. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Thoracentesis and thoracoscopy are used to diagnose malignant pleural effusions (MPE). Data on how sensitivity varies with tumour type is limited.
METHODS
Systematic review using PubMed was performed through August 2020 to determine the sensitivity of thoracentesis and thoracoscopy for MPE secondary to malignancy, by cancer type, and complication rates. Tests to identify sources of heterogeneity were performed. Study quality was assessed using Quality Assessment of Diagnostic Accuracy Studies (QUADAS)-2 and National Institutes of Health quality assessment tools. Publication bias was tested using funnel plots.
RESULTS
Meta-analyses for sensitivity of thoracentesis for MPE secondary to malignancy, mesothelioma and lung and breast cancer included 29, eight, 12 and nine studies, respectively. Pooled sensitivities were 0.643 (95% CI 0.592-0.692), 0.451 (95% CI 0.249-0.661), 0.738 (95% CI 0.659-0.836) and 0.820 (95% CI 0.700-0.917), respectively. For sensitivity of thoracoscopy for MPE secondary to malignancy and mesothelioma, 41 and 15 studies were included, respectively. Pooled sensitivities were 0.929 (95% CI 0.905-0.95) and 0.915 (95% CI 0.871-0.952), respectively. Pooled complication rates of thoracentesis and thoracoscopy were 0.041 (95% CI 0.025-0.051) and 0.040 (95% CI 0.029-0.052), respectively. Heterogeneity was significant for all meta-analyses. Funnel plots were asymmetric.
INTERPRETATION
Sensitivity of thoracentesis varied significantly per cancer type. Pooled complication rates were low. Awareness of how sensitivity of thoracentesis changes across cancers can improve decision-making when MPE is suspected.
Topics: Humans; Thoracentesis; Retrospective Studies; Pleural Effusion, Malignant; Mesothelioma; Mesothelioma, Malignant; Thoracoscopy
PubMed: 36543349
DOI: 10.1183/16000617.0053-2022 -
Lung Cancer (Amsterdam, Netherlands) Dec 2021The role of PET and integrated PET-CT in the diagnostic workup of suspected malignant pleural effusions is unknown. Earlier systematic reviews (published 2014 and 2015)... (Meta-Analysis)
Meta-Analysis Review
The role of PET and integrated PET-CT in the diagnostic workup of suspected malignant pleural effusions is unknown. Earlier systematic reviews (published 2014 and 2015) both included pleural pathology without effusion, and reached contradictory conclusions. Five studies have been published since the latest review. This systematic review and meta-analysis aims to summarise the evidence of PET and integrated PET-CT in predicting pleural malignancy in patients suspected of having malignant pleural effusions. A meta-analysis based on a systematic literature search in Cochrane Library, Medline, EMBASE and Clinicaltrials.gov was performed. Diagnostic studies evaluating the performance of PET or PET-CT in patients with suspected malignant pleural effusion, using pleural fluid cytology or histopathology as the reference test, and presenting sufficient data for constructing a 2x2 table were included. The quality of the studies was assessed by the Quality Assessment of Diagnostic Accuracy Studies-2 score. Subgroup analyses on image modality, interpretation method and known malignancy status pre index-test application were planned. Seven studies with low risk of bias were included. The pooled ability to separate benign from malignant effusions varied with image modality, interpretation method and known malignancy status pre index-test application. In studies using PET-CT, visual/qualitative image analysis was superior to semi-quantitative with positive (LR + ) and negative likelihood ratio (LR-) of 9.9 (4.5-15.3) respectively 0.1 (0.1-0.2). There was considerable heterogeneity among studies. In conclusion, visual/qualitative image analysis of integrated PET-CT seems to add relevant information in the work-up of suspected malignant pleural effusions with LR + and LR- close to rigorous pre-set cut-offs of > 10 and < 0.1. However, the quality of evidence was low due to inter-study heterogeneity, and inability to assess meta-bias. Clinical Trial Registration: The protocol was uploaded to the PROSPERO database (CRD42020213319) on the 13th of October 2020.
Topics: Fluorodeoxyglucose F18; Humans; Lung Neoplasms; Pleural Effusion; Pleural Effusion, Malignant; Pleural Neoplasms; Positron Emission Tomography Computed Tomography; Positron-Emission Tomography; Radiopharmaceuticals; Sensitivity and Specificity
PubMed: 34775214
DOI: 10.1016/j.lungcan.2021.10.018 -
Thoracic Surgery Clinics Nov 2020Despite multiple diagnostic toolkits, the diagnosis of diffuse malignant pleural mesothelioma relies primarily on proper histologic assessment. The definitive diagnosis...
Despite multiple diagnostic toolkits, the diagnosis of diffuse malignant pleural mesothelioma relies primarily on proper histologic assessment. The definitive diagnosis of diffuse malignant pleural mesothelioma is based on the pathologic assessment of tumor tissue, which can be obtained from core biopsy sampling, pleurectomy, or other more extensive resections, such as extrapleural pneumonectomy. Given its rarity and overlapping microscopic features with other conditions, the histologic diagnosis of diffuse malignant pleural mesothelioma is challenging. This review discusses the pathologic features and the differential diagnosis of diffuse malignant pleural mesothelioma, including select diagnostic pitfalls.
Topics: Biopsy; Diagnosis, Differential; Humans; Mesothelioma, Malignant; Pleural Neoplasms; Thoracic Surgical Procedures
PubMed: 33012427
DOI: 10.1016/j.thorsurg.2020.08.007 -
Pathology, Research and Practice Sep 2023Highly supported microRNAs (miRNAs) are key players in cancer development. Each of these miRNAs may act as an oncomir, a tumor-suppressor, or both in various cancers.... (Review)
Review
BACKGROUND
Highly supported microRNAs (miRNAs) are key players in cancer development. Each of these miRNAs may act as an oncomir, a tumor-suppressor, or both in various cancers. Mir-151a-5p is believed to be one of these miRNAs with diverse roles. We have conducted this systematic review to clarify the role of mir-151a-5p in formation of various cancers.
METHODS AND MATERIALS
We searched for existing articles in PubMed, Web of Science, Cochrane, Scopus, and RNAcentral databases up to November 2022. A total of 23 articles were qualified and included in the present systematic review. This review is registered on JBI at https://jbi.global/systematic-review-register. Expression levels, diagnostic and prognostic values, biological processes, and targeted downstream genes are included.
RESULTS
Assembled data indicate the expression levels of mir-151a-5p vary from down- to up-regulated based on the type of the cancer. Its functional role depends on the genetic profile of cancerous tissue. Results mostly point to the oncogenic role of this miRNA in Pituitary adenomas, Acute Myeloid Leukemia (AML), Endometrial, Lung, Barrett's carcinogenesis, Colorectal, Myelodysplastic syndromes, Hepatocellular carcinoma and Breast cancers, as its inhibited targets seem to be controlling several signaling pathways, cell adhesion, and cell cycle. At the same time, tumor-suppressing role has also been observed only in Malignant Pleural Mesothelioma, Central Nerve System (CNS) lymphoma, Chronic Myeloid and Acute Lymphocytic Leukemia. Two types of cancers, prostate and colon, show contradictory results as there are studies supporting both up- and down-regulation in these cancers. Pituitary adenomas, Barrett's carcinogenesis and CNS lymphomas are top cancers diagnosed with mir-151-5p. However, prognostic feature is only applicable to Lung adenocarcinoma.
DISCUSSION
Based on the present findings and further studies in the future, mir-151a-5p may be used as diagnostic and prognostic biomarkers or even a therapeutic target in cancer studies.
DATA AVAILABILITY STATEMENT
The articles used in this study can be found with the defined search phrase in mentioned databases. A list of selected articles will be available on reasonable requests.
Topics: Male; Humans; Pituitary Neoplasms; MicroRNAs; Carcinogenesis; Cell Transformation, Neoplastic; Genes, Tumor Suppressor; Gene Expression Regulation, Neoplastic
PubMed: 37562284
DOI: 10.1016/j.prp.2023.154576