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Targeted Oncology Jan 2024Malignant pleural mesothelioma (MPM) is a rare and challenging cancer associated with asbestos fiber exposure, which offers limited treatment options. Historically,... (Review)
Review
Malignant pleural mesothelioma (MPM) is a rare and challenging cancer associated with asbestos fiber exposure, which offers limited treatment options. Historically, platinum-based chemotherapy has been the primary approach, but recent developments have introduced immunotherapy as a promising alternative for the treatment of this disease. Nevertheless, the unique growth patterns and occasionally ambiguous progressive characteristics of MPM make the interpretation of radiological assessments complex. Immunotherapy further complicates matters by introducing unconventional treatment response patterns such as hyperprogression and pseudoprogression. Consequently, there is a growing imperative to integrate the standard RECIST criteria with the mesothelioma-specific mRECIST criteria (version 1.1), as outlined in iRECIST. This comprehensive review is driven by the intent to provide a valuable resource for radiologists and clinicians engaged in the diagnosis, treatment, and monitoring of MPM in the era of immunotherapy. Specifically, the current imaging methods employed for staging and follow-up will be exposed and discussed, with a focus on the technical specificities and the mRECIST 1.1 methodology. Furthermore, we will provide a discussion about major clinical trials related to the use of immunotherapy in MPM patients. Finally, the latest advancements in radiomics, the applications of artificial intelligence in MPM, and their potential impact on clinical practice for prognosis and therapy, are discussed.
Topics: Humans; Mesothelioma, Malignant; Immune Checkpoint Inhibitors; Artificial Intelligence; Pleural Neoplasms; Lung Neoplasms; Combined Modality Therapy
PubMed: 38063957
DOI: 10.1007/s11523-023-01017-w -
Therapeutic Advances in Respiratory... 2024The prognosis of malignant pleural effusion (MPE) is poor. A timely and accurate diagnosis is the prerequisite for managing MPE patients. Carbohydrate antigen 72-4...
BACKGROUND
The prognosis of malignant pleural effusion (MPE) is poor. A timely and accurate diagnosis is the prerequisite for managing MPE patients. Carbohydrate antigen 72-4 (CA72-4) is a diagnostic tool for MPE.
OBJECTIVE
We aimed to evaluate the diagnostic accuracy of pleural fluid CA72-4 for MPE.
DESIGN
A prospective, preregistered, and double-blind diagnostic test accuracy study.
METHODS
We prospectively enrolled participants with undiagnosed pleural effusions from two centers in China (Hohhot and Changshu). CA72-4 concentration in pleural fluid was measured by electrochemiluminescence. Its diagnostic accuracy for MPE was evaluated by a receiver operating characteristic (ROC) curve. The net benefit of CA72-4 was determined by a decision curve analysis (DCA).
RESULTS
In all, 153 participants were enrolled in the Hohhot cohort, and 58 were enrolled in the Changshu cohort. In both cohorts, MPE patients had significantly higher CA72-4 levels than benign pleural effusion (BPE) patients. At a cutoff value of 8 U/mL, pleural fluid CA72-4 had a sensitivity, specificity, and area under the ROC curve (AUC) of 0.46, 1.00, and 0.79, respectively, in the Hohhot cohort. In the Changshu cohort, CA72-4 had a sensitivity, specificity, and AUC of 0.27, 0.94, and 0.86, respectively. DCA revealed the relatively high net benefit of CA72-4 determination. In patients with negative cytology, the AUC of CA72-4 was 0.67.
CONCLUSION
Pleural fluid CA72-4 helps differentiate MPE and BPE in patients with undiagnosed pleural effusions.
Topics: Humans; Diagnostic Tests, Routine; Pleural Effusion; Pleural Effusion, Malignant; Prospective Studies
PubMed: 38189269
DOI: 10.1177/17534666231222333 -
International Immunopharmacology Jan 2024The inhibitory effect of γδT17 cells on the formation of murine malignant pleural effusions (MPE) has been established. However, there is limited understanding...
BACKGROUND
The inhibitory effect of γδT17 cells on the formation of murine malignant pleural effusions (MPE) has been established. However, there is limited understanding regarding the phenotypic characterization of γδ T cells in MPE patients and their recruitment to the pleural cavity.
METHODS
We quantified γδ T cell prevalence in pleural effusions and corresponding peripheral blood from malignant and benign patients using immunohistochemistry and flow cytometry. The expression of effector memory phenotype, stimulatory/inhibitory/chemokine receptors and cytokines on γδ T cells in MPE was analyzed using multicolor flow cytometry. The infiltration of γδ T cells in MPE was assessed through immunofluorescence, ELISA, flow cytometry and transwell migration assay.
RESULTS
We observed a significant infiltration of γδ T cells in MPE, surpassing the levels found in blood and benign pleural effusion. γδ T cells in MPE exhibited heightened expression of CD56 and an effector memory phenotype, while displaying lower levels of PD-1. Furthermore, γδ T cells in MPE showed higher levels of cytokines (IFN-γ, IL-17A and IL-22) and chemokine receptors (CCR2, CCR5 and CCR6). CCR2 expression was notably higher in the Vδ2 subtype compared to Vδ1 cells. Moreover, the complement C5a enhanced cytokine release by γδ T cells, upregulated CCR2 expression in Vδ2 subsets, and stimulated the production of chemokines (CCL2, CCL7 and CCL20) in MPE. In vitro utilizing CCR2 neutralising and C5aR antagonist significantly reduced the recruitment of γδ T cells.
CONCLUSIONS
γδ T cells infiltrate MPE by overexpressing CCR2 and exhibit hightened inflammation, which is further augmented by C5a.
Topics: Animals; Humans; Mice; Chemotaxis; Cytokines; Inflammation; Pleural Effusion; Pleural Effusion, Malignant; Receptors, Antigen, T-Cell, gamma-delta; Receptors, Chemokine; Complement C5a
PubMed: 38071913
DOI: 10.1016/j.intimp.2023.111332 -
Seminars in Respiratory and Critical... Aug 2023
Topics: Humans; Pleural Diseases; Pleural Effusion
PubMed: 37429294
DOI: 10.1055/s-0043-1769613 -
Molecular Oncology Apr 2024Mesothelioma is a type of late-onset cancer that develops in cells covering the outer surface of organs. Although it can affect the peritoneum, heart, or testicles, it... (Review)
Review
Mesothelioma is a type of late-onset cancer that develops in cells covering the outer surface of organs. Although it can affect the peritoneum, heart, or testicles, it mainly targets the lining of the lungs, making pleural mesothelioma (PMe) the most common and widely studied mesothelioma type. PMe is caused by exposure to fibres of asbestos, which when inhaled leads to inflammation and scarring of the pleura. Despite the ban on asbestos by most Western countries, the incidence of PMe is on the rise, also facilitated by a lack of specific symptomatology and diagnostic methods. Therapeutic options are also limited to mainly palliative care, making this disease untreatable. Here we present an overview of biological aspects underlying PMe by listing genetic and molecular mechanisms behind its onset, aggressive nature, and fast-paced progression. To this end, we report on the role of deubiquitinase BRCA1-associated protein-1 (BAP1), a tumour suppressor gene with a widely acknowledged role in the corrupted signalling and metabolism of PMe. This review aims to enhance our understanding of this devastating malignancy and propel efforts for its investigation.
Topics: Humans; Mesothelioma; Mesothelioma, Malignant; Pleural Neoplasms; Asbestos; Lung Neoplasms
PubMed: 38459714
DOI: 10.1002/1878-0261.13591 -
Journal of Thoracic Oncology : Official... Sep 2023Pleural mesothelioma (PM) is an aggressive malignancy with increasing prevalence and poor prognosis. Real-life data are a unique approach to reflect the reality of PM...
European Epidemiology of Pleural Mesothelioma-Real-Life Data From a Joint Analysis of the Mesoscape Database of the European Thoracic Oncology Platform and the European Society of Thoracic Surgery Mesothelioma Database.
INTRODUCTION
Pleural mesothelioma (PM) is an aggressive malignancy with increasing prevalence and poor prognosis. Real-life data are a unique approach to reflect the reality of PM epidemiology, treatment, and prognosis in Europe.
METHODS
A joint analysis of the European Thoracic Oncology Platform Mesoscape and the European Society of Thoracic Surgeons (ESTS) databases was performed to better understand the characteristics and epidemiology of PM, including histologic subtype, staging, and treatment. Overall survival (OS) was assessed, adjusting for parameters of clinical interest.
RESULTS
The analysis included 2766 patients (Mesoscape: 497/10 centers/ESTS: 2269/77 centers). The primary histologic subtype was epithelioid (71%), with 57% patients on stages III to IV. Within Mesoscape, the patients received either multimodality (59%) or palliative intention treatment (41%). The median follow-up was 47.2 months, on the basis of 1103 patients (Mesoscape: 491/ESTS: 612), with 823 deaths, and median OS was 17.4 months. In multivariable analysis, female sex, epithelioid subtype, and lower stage were associated with longer OS, when stratifying by cohort, age, and Eastern Cooperative Oncology Group Performance Status. Within Mesoscape, multimodality treatment including surgery was predictive of longer OS (hazard ratio = 0.56, 95% confidence interval: 0.45-0.69), adjusting for sex, histologic subtype, and Eastern Cooperative Oncology Group Performance Status. Overall, surgical candidates with a macroscopic complete resection had a significantly longer median OS compared with patients with R2 (25.2 m versus 16.4 m; log-rank p < 0.001).
CONCLUSIONS
This combined European Thoracic Oncology Platform/ESTS database analysis offers one of the largest databases with detailed clinical and pathologic outcome. Our finding reflects a benefit for selected patients that undergo multimodality treatment, including macroscopic complete resection, and represents a valuable resource to inform the epidemiology and treatment options for individual patients.
Topics: Humans; Female; Thoracic Surgery; Lung Neoplasms; Mesothelioma, Malignant; Mesothelioma; Pleural Neoplasms
PubMed: 37356802
DOI: 10.1016/j.jtho.2023.06.011 -
Journal of Translational Medicine Sep 2023Metagenomic next-generation sequencing (mNGS) has become a powerful tool for pathogen detection, but the value of human sequencing reads generated from it is...
BACKGROUND
Metagenomic next-generation sequencing (mNGS) has become a powerful tool for pathogen detection, but the value of human sequencing reads generated from it is underestimated.
METHODS
A total of 138 patients with pleural effusion (PE) were diagnosed with tuberculous pleurisy (TBP, N = 82), malignant pleural effusion (MPE, N = 35), or non-TB infection (N = 21), whose PE samples all underwent mNGS analysis. Clinical TB tests including culture, Acid-Fast Bacillus (AFB) test, Xpert, and T-SPOT, were performed. To utilize mNGS for MPE identification, 25 non-MPE samples (20 TBP and 5 non-TB infection) were randomly selected to set human chromosome copy number baseline and generalized linear modeling was performed using copy number variant (CNV) features of the rest 113 samples (35 MPE and 78 non-MPE).
RESULTS
The performance of TB detection was compared among five methods. T-SPOT demonstrated the highest sensitivity (61% vs. culture 32%, AFB 12%, Xpert 35%, and mNGS 49%) but with the highest false-positive rate (10%) as well. In contrast, mNGS was able to detect TB-genome in nearly half (40/82) of the PE samples from TBP subgroup, with 100% specificity. To evaluate the performance of using CNV features of the human genome for MPE prediction, we performed the leave-one-out cross-validation (LOOCV) in the subcohort excluding the 25 non-MPE samples for setting copy number standards, which demonstrated 54.1% sensitivity, 80.8% specificity, 71.7% accuracy, and an AUC of 0.851.
CONCLUSION
In summary, we exploited the value of human and non-human sequencing reads generated from mNGS, which showed promising ability in simultaneously detecting TBP and MPE.
Topics: Humans; Tuberculosis, Pleural; Pleural Effusion, Malignant; Pleural Effusion; High-Throughput Nucleotide Sequencing; Metagenomics; Sensitivity and Specificity
PubMed: 37777783
DOI: 10.1186/s12967-023-04492-x -
Tidsskrift For Den Norske Laegeforening... Apr 2024Pneumothorax following shoulder arthroscopy, although rare, is documented in over 30 PubMed case reports as occurring during or within 10 hours post-procedure.
BACKGROUND
Pneumothorax following shoulder arthroscopy, although rare, is documented in over 30 PubMed case reports as occurring during or within 10 hours post-procedure.
CASE PRESENTATION
A fit septuagenarian underwent a two-hour arthroscopic rotator cuff repair with IV anaesthesia and laryngeal mask airway, without a nerve block. With one hour remaining of the operation, the patient had desaturation and hypotension. Lung sliding was absent on ultrasound and x-ray confirmed left-sided tension pneumothorax. Successful thoracic drain insertion and lung re-expansion facilitated his recovery, allowing discharge after 24 hours and symptom-free status at 6 months.
INTERPRETATION
This case highlights pneumothorax as an uncommon yet possible post-arthroscopic event. The speculated aetiology is the surgical procedure, where pump-induced pressure fluctuations may displace air into surrounding tissue. Instances of pneumomediastinum and subcutaneous emphysema without pneumothorax suggest arthroscopic origin of air. Prompt perioperative ultrasound can aid in detecting such critical complications.
Topics: Humans; Pneumothorax; Male; Arthroscopy; Middle Aged; Rotator Cuff Injuries
PubMed: 38651717
DOI: 10.4045/tidsskr.23.0542 -
PLoS Neglected Tropical Diseases Dec 2023Pulmonary paragonimiasis, a food-borne zoonotic helminthiasis, is a parasitic disease of the lung caused by infection with trematodes species of the genus Paragonimus....
BACKGROUND
Pulmonary paragonimiasis, a food-borne zoonotic helminthiasis, is a parasitic disease of the lung caused by infection with trematodes species of the genus Paragonimus. Although pneumothorax has been reported as occuring with paragonimiasis, to date no study has been performed concerning the clinical features and predictive risk factors for this condition.
METHODS
This retrospective study, which aims to fill this gap, was conducted at Jeonbuk National University Hospital. All patients (aged ≥19 years) were diagnosed with paragonimiasis between May 2011 and December 2021. Medical records were reviewed and information concerning age, sex, vital signs, underlying diseases, clinical signs and symptoms, laboratory findings, radiologic findings, treatment, and clinical outcomes was collected. An odds ratio (OR) for the risk factors associated with pneumothorax was calculated using the binary logistic regression model.
RESULTS
Among 179 consecutive patients diagnosed with pulmonary paragonimiasis, the postive rate of pneumothorax was 10.6% (19/179). Pneumothorax occurred mostly in the right lung (78.9%, 15/19), and intrapulmonary parenchymal lesions showed an ipsilateral relationship with pneumothorax (94.7%, 18/19). Fifteen patients (78.9%, 15/19) of pneumothorax associated with pulmonary paragonimiasis are accompanied by pleural effusion. Most of patients with pneumothorax (89.5%, 17/19) underwent chest tube insertion as a first treatment. Three patients (15.8%) showed relapses but in no case was a death recorded. Asthma (odds ratio [OR] 8.10, 95% confidence interval [CI] 1.43-45.91), chest pain (OR 8.15, 95% CI 2.70-24.58), and intrapulmonary lesions (OR 8.94, 95% CI 1.12-71.36) were independent risk factors for pulmonary paragonimiasis-associated pneumothorax.
CONCLUSIONS
Our findings suggest that clinicians should keep in mind the possibility of pneumothorax when approached by patients with pulmonary paragonimiasis complaining of chest pain, accompanied by intrapulmonary lesions or with asthma as an underlying disease.
Topics: Animals; Humans; Paragonimiasis; Pneumothorax; Retrospective Studies; Paragonimus; Risk Factors; Asthma; Chest Pain
PubMed: 38100524
DOI: 10.1371/journal.pntd.0011828 -
Journal of the American College of... Jun 2024Pleural effusions are categorized as transudative or exudative, with transudative effusions usually reflecting the sequala of a systemic etiology and exudative...
Pleural effusions are categorized as transudative or exudative, with transudative effusions usually reflecting the sequala of a systemic etiology and exudative effusions usually resulting from a process localized to the pleura. Common causes of transudative pleural effusions include congestive heart failure, cirrhosis, and renal failure, whereas exudative effusions are typically due to infection, malignancy, or autoimmune disorders. This document summarizes appropriateness guidelines for imaging in four common clinical scenarios in patients with known or suspected pleural effusion or pleural disease. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.
Topics: Humans; Pleural Effusion; Evidence-Based Medicine; United States; Societies, Medical; Pleural Diseases; Diagnostic Imaging; Diagnosis, Differential
PubMed: 38823955
DOI: 10.1016/j.jacr.2024.02.013