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Annals of Oncology : Official Journal... Feb 2022
Topics: Humans; Mesothelioma; Mesothelioma, Malignant; Pleural Neoplasms
PubMed: 34883215
DOI: 10.1016/j.annonc.2021.11.019 -
Pathology, Research and Practice Dec 2021The role of 2-deoxy-2-[F]fluoro-D-glucose positron emission tomography/computed tomography ([F]FDG PET/CT) in evaluating induction chemotherapy in pleural mesothelioma...
The role of 2-deoxy-2-[F]fluoro-D-glucose positron emission tomography/computed tomography ([F]FDG PET/CT) in evaluating induction chemotherapy in pleural mesothelioma (PM) patients is debated. We compared histology at tumor sites with high versus low [F]FDG uptake in order to define a morphologic correlate for persistent metabolic activity. Twenty PM patients with talc pleurodesis and induction chemotherapy followed by extrapleural pleuro-pneumonectomy (EPP, n = 17) or tumor debulking (n = 3) were included. All patients received a PET/CT scan prior to surgery. Orthogonal tissue sections of pleural rind (n total=86) were taken at areas of maximum standardized uptake value (SUV, n = 53) and of low [F]FDG uptake (n = 33) and scored on hematoxylin-eosin and immunohistochemical stainings. Total metabolic activity was scored semiquantitatively. Mean SUV of hot and cold spots correlated with total metabolic activity per patient, but no correlation was found with ypT and tumor cells were present in both hot and cold areas. SUV of only hot spots and cold versus hot spots as well as cold versus hot patients correlated with increased thickness of total pleural rind and fibrosis reaction, but not thickness of vital tumor cells or giant cell reaction. They further correlated with increased expression of glucose transporter 1 (GLUT1) in giant cells but not mesothelioma amount, density, vitality or vascularization. Biphasic histology was associated with SUV in only hot spots and higher total metabolic activity (all p-values <0.05). Interpretation of [F]FDG PET/CT in PM patients is difficult after talc pleurodesis and induction chemotherapy. High glucose turnover is mostly related to fibro-inflammatory remodeling of the pleural rind and GLUT1 transporter expression in giant cells. Response assessment using this technology should only be done to assess extra-thoracic lesions.
Topics: Female; Fluorodeoxyglucose F18; Humans; Induction Chemotherapy; Male; Mesothelioma; Neoadjuvant Therapy; Neoplasm Staging; Pleura; Pleural Neoplasms; Pleurodesis; Positron Emission Tomography Computed Tomography; Radiopharmaceuticals; Talc; Treatment Outcome
PubMed: 34749212
DOI: 10.1016/j.prp.2021.153660 -
Cancer Medicine Jun 2023The role of postoperative radiotherapy (PORT) in malignant pleural mesothelioma (MPM) remains controversial and the eighth edition TNM staging scheme for MPM has not...
OBJECTIVES
The role of postoperative radiotherapy (PORT) in malignant pleural mesothelioma (MPM) remains controversial and the eighth edition TNM staging scheme for MPM has not been fully verified. We aimed to develop an individualized prediction model for identifying optimal candidates for PORT among MPM patients who received surgery plus chemotherapy and externally validate the performance of the new TNM staging scheme.
MATERIALS AND METHODS
Detailed characteristics of MPM patients during 2004-2015 were retrieved from SEER registries. Propensity score matching (PSM) was conducted to reduce disparities of baseline characteristics (age, sex, histologic type, stage, and type of surgery) between the PORT group and no-PORT group. A novel nomogram was constructed based on independent prognosticators identified by multivariate Cox regression model. The discriminatory performance and degree of calibration were evaluated. We stratified patients into different risk groups according to nomogram total scores and estimated the survival benefit of PORT in different subgroups in order to identify the optimal candidates.
RESULTS
We identified 596 MPM patients, among which 190 patients (31.9%) received PORT. PORT conferred significant survival benefit in the unmatched population, while there was no significant survival difference favoring PORT in the matched population. The C-index of the new TNM staging scheme was closed to 0.5, which represented a poor discriminatory ability. A novel nomogram was constructed based on clinicopathological factors, including age, sex, histology, and N stage. We stratified patients into three risk groups. Subgroup analyses indicated that PORT was beneficial for high-risk group (p = 0.003) rather than low-risk group (p = 0.965) and intermediate-risk group (p = 0.661).
CONCLUSION
We established a novel predictive model, which could make individualized prediction of survival benefit of PORT for MPM and could compensate for weakness in TNM staging system.
Topics: Humans; Mesothelioma, Malignant; Mesothelioma; Pleural Neoplasms; Lung Neoplasms; Neoplasm Staging; Prognosis
PubMed: 37076977
DOI: 10.1002/cam4.5955 -
International Journal of Molecular... Nov 2021Malignant pleural mesothelioma (MPM) is an aggressive tumor mainly associated with asbestos exposure and is characterized by a very difficult pharmacological approach.... (Review)
Review
Malignant pleural mesothelioma (MPM) is an aggressive tumor mainly associated with asbestos exposure and is characterized by a very difficult pharmacological approach. One of the molecular mechanisms associated with cancer onset and invasiveness is the epithelial-to-mesenchymal transition (EMT), an event induced by different types of inducers, such as transforming growth factor β (TGFβ), the main inducer of EMT, and oxidative stress. MPM development and metastasis have been correlated to EMT; On one hand, EMT mediates the effects exerted by asbestos fibers in the mesothelium, particularly via increased oxidative stress and TGFβ levels evoked by asbestos exposure, thus promoting a malignant phenotype, and on the other hand, MPM acquires invasiveness via the EMT event, as shown by an upregulation of mesenchymal markers or, although indirectly, some miRNAs or non-coding RNAs, all demonstrated to be involved in cancer onset and metastasis. This review aims to better describe how EMT is involved in driving the development and invasiveness of MPM, in an attempt to open new scenarios that are useful in the identification of predictive markers and to improve the pharmacological approach against this aggressive cancer.
Topics: Biomarkers, Tumor; Epithelial-Mesenchymal Transition; Humans; Mesothelioma, Malignant; MicroRNAs; Neoplasm Metastasis; Neoplasm Proteins; Pleural Neoplasms; RNA, Neoplasm; Transforming Growth Factor beta
PubMed: 34830097
DOI: 10.3390/ijms222212216 -
Multimedia Manual of Cardiothoracic... Jan 2018Surgical staging of lung and pleural cancers is crucial for planning treatment and assessing prognosis. In some cases, we need to explore both the mediastinum and the...
Surgical staging of lung and pleural cancers is crucial for planning treatment and assessing prognosis. In some cases, we need to explore both the mediastinum and the pleural cavity to confirm or rule out tumor dissemination. The combination of video-assisted mediastinoscopic lymphadenectomy (VAMLA) and thoracoscopy through a single transcervical incision allows the surgeon to widen the range of the exploration and improve the staging for lung and pleural cancers. VAMLA consists of complete removal of the mediastinal fat and lymph nodes of the subcarinal space, the right paratracheal and pretracheal areas, and the left paratracheal space. Once this mediastinal tissue is removed, the right mediastinal pleura can be identified and incised. A 30o thoracoscope is then inserted through the video-mediastinoscope into the pleural cavity to obtain samples of pleural fluid and biopsies of the parietal pleura and lung nodules, if present. In the case of left-sided thoracoscopy the access route to the left pleural cavity is anterior to the aortic arch, as for extended cervical mediastinoscopy. The combination of VAMLA and thoracoscopy is useful for exploring the mediastinum and the pleural space from a single incision and in the same surgical setting as the transcervical approach.
Topics: Biopsy; Humans; Lung Neoplasms; Lymph Node Excision; Lymph Nodes; Mediastinoscopy; Mediastinum; Neoplasm Staging; Pleural Cavity; Pleural Neoplasms; Thoracic Surgery, Video-Assisted; Thoracoscopy; Video-Assisted Surgery
PubMed: 29384599
DOI: 10.1510/mmcts.2018.004 -
Thoracic Surgery Clinics Nov 2020In the absence of standardized treatment algorithms for patients with malignant pleural mesothelioma, one of the main difficulties remains patient allocation to... (Review)
Review
In the absence of standardized treatment algorithms for patients with malignant pleural mesothelioma, one of the main difficulties remains patient allocation to therapies with potential benefit. This article discusses clinical, radiologic, pathologic, and molecular prognostic factors as well as genetic background leading to preoperative identification of benefit from surgery, which have been investigated over the past years to simplify and at the same time specify patient selection for surgical treatment.
Topics: Humans; Mesothelioma, Malignant; Patient Selection; Pleural Neoplasms; Preoperative Care; Prognosis
PubMed: 33012431
DOI: 10.1016/j.thorsurg.2020.08.003 -
Cells Sep 2022Malignant pleural mesothelioma (MPM) is a fatal disease of respiratory system. Despite the availability of invasive biomarkers with promising results, there are still...
Malignant pleural mesothelioma (MPM) is a fatal disease of respiratory system. Despite the availability of invasive biomarkers with promising results, there are still significant diagnostic and therapeutic challenges in the treatment of MPM. One of three main mesothelioma cell types, epithelioid mesothelioma makes up approximately 70% of all mesothelioma cases. Different observational findings are under process, but the molecular heterogeneity and pathogenesis of epithelioid malignant pleural mesothelioma (eMPM) are still not well understood. Through molecular analysis, expression profiling data were used to determine the possibility and optimal number of eMPM molecular subtypes. Next, clinicopathological characteristics and different molecular pathways of each subtype were analyzed to prospect the clinical applications and advanced mechanisms of eMPM. In this study, we identified two distinct epithelioid malignant pleural mesothelioma subtypes with distinct gene expression patterns. Subtype I eMPMs were involved in steroid hormone biosynthesis, porphyrin and chlorophyll metabolism, and drug metabolism, while subtype II eMPMs were involved in rational metabolism, tyrosine metabolism, and chemical carcinogenesis pathways. Additionally, we identified potential subtype-specific therapeutic targets, including CCNE1, EPHA3, RNF43, ROS1, and RSPO2 for subtype I and CDKN2A and RET for subtype II. Considering the need for potent diagnostic and therapeutic biomarkers for eMPM, we are anticipating that our findings will help both in exploring underlying mechanisms in the development of eMPM and in designing targeted therapy for eMPM.
Topics: Chlorophyll; Hormones; Humans; Lung Neoplasms; Mesothelioma; Mesothelioma, Malignant; Pleural Neoplasms; Porphyrins; Proto-Oncogene Proteins; Steroids; Tyrosine
PubMed: 36139498
DOI: 10.3390/cells11182924 -
Respirology (Carlton, Vic.) Jan 2017Malignant pleural effusion (MPE) affects >90% of mesothelioma patients. Research on MPE has focused on its physical impact on breathlessness; MPE is rich in growth...
BACKGROUND AND OBJECTIVE
Malignant pleural effusion (MPE) affects >90% of mesothelioma patients. Research on MPE has focused on its physical impact on breathlessness; MPE is rich in growth mediators but its contribution to tumour biology has not been investigated. We aimed to examine the potential effects of MPE in promoting growth, migration and chemo-resistance of mesothelioma.
METHODS
Pleural fluid samples from 151 patients (56 mesothelioma, 60 metastatic pleural cancer and 35 benign) were used. Seven validated human mesothelioma cell lines and three primary cultured mesothelioma lines were employed.
RESULTS
Pleural fluid from mesothelioma patients (diluted to 30%) consistently stimulated cell proliferation (trypan-blue cell viability assay) in five mesothelioma cell lines tested by (median) 2.23-fold over controls (all P < 0.0001). The fluid also induced cell migration by (median) 2.13-fold in six mesothelioma cell lines using scratch-wound assay. In a murine flank model of mesothelioma, tumour infused with daily instillations of pleural fluid grew significantly faster over saline controls (median 52.5 cm vs 28.0 cm at day 13, P = 0.028). Addition of MPE (diluted to 30%) to culture media significantly protected mesothelioma from cisplatin/pemetrexed-induced cell death in all three cell lines tested (median fold reduction of 1.29, 1.98 and 3.90, all P < 0.001 vs control). The growth effects of matched pleural fluid and cultured mesothelioma cells from the same patients did not differ significantly from unmatched pairs.
CONCLUSION
This 'proof-of-concept' study reveals potent biological capabilities of malignant pleural fluid in mesothelioma pathobiology.
Topics: Animals; Antineoplastic Agents; Cell Line, Tumor; Cell Movement; Cell Proliferation; Cell Survival; Cisplatin; Drug Resistance, Neoplasm; Exudates and Transudates; Humans; Lung Neoplasms; Mesothelioma; Mesothelioma, Malignant; Mice; Pemetrexed; Pleural Effusion, Malignant; Pleural Neoplasms
PubMed: 27560254
DOI: 10.1111/resp.12874 -
In Vivo (Athens, Greece) 2018A strategy for improving survival of malignant pleural mesothelioma (MPM) patients is earlier diagnosis paired with earlier stage implementation of therapeutic...
BACKGROUND/AIM
A strategy for improving survival of malignant pleural mesothelioma (MPM) patients is earlier diagnosis paired with earlier stage implementation of therapeutic interventions. This study aimed to determine the clinical signs of early-stage MPM to aid an earlier diagnosis and earlier-stage intervention.
MATERIALS AND METHODS
Out of the 72 cases in our institution, 40 cases with F-FDG-PET/CT-negative MPM were retrospectively identified between 2007 and 2015. Overall survival rates were determined and compared with pathological features, histology, and treatment.
RESULTS
The biphasic histological type of early-stage MPM was characterized by poor prognosis (p=0.0006). Additionally, the cytology-negative group (Class III and below) showed significantly shorter survival times (p=0.0290). There was no significant difference in survival between patients who received pleurectomy and those who received chemotherapy only (p=0.6991). Bimodal therapy resulted in a longer survival rate than trimodal therapy.
CONCLUSION
In early-stage PET-negative MPM cases, biphasic histology and pleural effusion of Class III and below correlated with a poor prognosis. Surgical treatment using pleurectomy/decortication resulted in higher patient survival outcomes than therapy with extrapleural pneumonectomy.
Topics: Aged; Combined Modality Therapy; Female; Fluorodeoxyglucose F18; Humans; Kaplan-Meier Estimate; Lung Neoplasms; Male; Mesothelioma; Mesothelioma, Malignant; Middle Aged; Neoplasm Staging; Pleural Neoplasms; Positron Emission Tomography Computed Tomography; Treatment Outcome
PubMed: 30150440
DOI: 10.21873/invivo.11360 -
The European Respiratory Journal Jan 2024The pleural lining of the thorax regulates local immunity, inflammation and repair. A variety of conditions, both benign and malignant, including pleural mesothelioma,...
The pleural lining of the thorax regulates local immunity, inflammation and repair. A variety of conditions, both benign and malignant, including pleural mesothelioma, can affect this tissue. A lack of knowledge concerning the mesothelial and stromal cells comprising the pleura has hampered the development of targeted therapies. Here, we present the first comprehensive single-cell transcriptomic atlas of the human parietal pleura and demonstrate its utility in elucidating pleural biology. We confirm the presence of known universal fibroblasts and describe novel, potentially pleural-specific, fibroblast subtypes. We also present transcriptomic characterisation of multiple models of benign and malignant mesothelial cells, and characterise these through comparison with transcriptomic data. While bulk pleural transcriptomes have been reported previously, this is the first study to provide resolution at the single-cell level. We expect our pleural cell atlas will prove invaluable to those studying pleural biology and disease. It has already enabled us to shed light on the transdifferentiation of mesothelial cells, allowing us to develop a simple method for prolonging mesothelial cell differentiation .
Topics: Humans; Pleura; Mesothelioma; Mesothelioma, Malignant; Pleural Neoplasms; Gene Expression Profiling
PubMed: 38212075
DOI: 10.1183/13993003.00143-2023