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Interactive Cardiovascular and Thoracic... Oct 2021Meningiomas are the most common intracranial tumours in adults and they are infrequently associated with a metastasis clinical course. Pleural metastases are extremely...
Meningiomas are the most common intracranial tumours in adults and they are infrequently associated with a metastasis clinical course. Pleural metastases are extremely rare and no guidelines on a specific treatment have been established. When localized, surgical resection is the mainstay of treatment, but there is a high risk of pleural recurrence. We aimed to describe a novel surgical approach in pleural metastasis of meningiomas. We report the case of a 41-year-old man with the medical history of surgically resected intracranial atypical meningioma. Nine years after diagnosis of atypical meningioma, a CT scan of the chest disclosed 10 pleural implants gathered in the fissure, in the paramediastinal pleura and at the base of the left hemithorax. Surgical resection was decided. Parietal and mediastinal pleura resection with visceral pleural lesions removal were performed. Cytoreductive surgery was associated with intrathoracic hyperthermic chemotherapy. Postoperative course was uneventful and no adjuvant therapy was undertaken. The patient is free of pleural recurrence 12 months post operatively. The present case report suggests that cytoreductive surgery with intrathoracic hyperthermic chemotherapy is feasible and safe in pleural metastasis from meningioma. Prolonged follow-up and prospective studies are mandatory to assess its oncological benefit.
Topics: Adult; Humans; Hyperthermia, Induced; Male; Meningeal Neoplasms; Meningioma; Pleura; Pleural Neoplasms; Prospective Studies
PubMed: 34160042
DOI: 10.1093/icvts/ivab174 -
Acta Cytologica 2023In most cases, the diagnostic workup of pleural mesotheliomas (MPMs) starts with cytological examination of pleural effusion, but histology is needed to confirm the...
INTRODUCTION
In most cases, the diagnostic workup of pleural mesotheliomas (MPMs) starts with cytological examination of pleural effusion, but histology is needed to confirm the diagnosis. The introduction of BAP1 and methylthio-adenosine phosphorylase (MTAP) immunohistochemistry has become a powerful tool to confirm the malignant nature of mesothelial proliferations also in cytological specimens. The objective of this study was to determine the concordance of BAP1, MTAP, and p16 expression between cytological and histological samples of patients with MPM.
METHODS
Immunohistochemistry of BAP1, MTAP, and p16 was performed on cytological samples and compared with the corresponding histological specimen of 25 patients with MPM. Inflammatory and stromal cells served as positive internal control for all three markers. In addition, samples of 11 patients with reactive mesothelial proliferations served as an external control group.
RESULTS
Loss of BAP1, MTAP, and p16 expression was found in 68%, 72%, and 92% of MPM, respectively. Loss of MTAP was associated with loss of p16 expression in all cases. Concordance of BAP1 between cytological and corresponding histological samples was 100% (kappa coefficient 1; p = 0.008). For MTAP and p16, kappa coefficient was 0.9 (p = 0.01) and 0.8 (p = 0.7788), respectively.
CONCLUSIONS
Concordant BAP1, MTAP, and p16 expression is found between cytological and corresponding histological samples, indicating that a reliable diagnosis of MPM can be made on cytology only. Of the three markers, BAP1 and MTAP are most reliable in distinguishing malignant from reactive mesothelial proliferations.
Topics: Humans; Immunohistochemistry; Lung Neoplasms; Tumor Suppressor Proteins; Mesothelioma, Malignant; Mesothelioma; Pleural Neoplasms; Biomarkers, Tumor; Diagnosis, Differential; Ubiquitin Thiolesterase
PubMed: 36889303
DOI: 10.1159/000530002 -
Cancer Reports (Hoboken, N.J.) Apr 2024Extrapleural pneumonectomy (EPP) is a complex surgical procedure involving en-bloc resection of the parietal and visceral pleura, lung, pericardium, and ipsilateral...
BACKGROUND
Extrapleural pneumonectomy (EPP) is a complex surgical procedure involving en-bloc resection of the parietal and visceral pleura, lung, pericardium, and ipsilateral diaphragm. Small case series of pleural-based sarcoma of predominantly pediatric patients suggest EPP may be a life-prolonging surgical option. We aimed to describe the characteristics and outcomes of adults who underwent EPP at a specialized sarcoma center.
METHODS
Clinicopathologic variables, surgical details, and follow-up information were extracted for patients undergoing EPP for pleural-based sarcoma between August 2017 and December 2020. Primary outcomes were event-free survival (EFS) and overall survival (OS) from the date of EPP. Secondary outcomes were disease-free interval (DFI) prior to EPP, and early and late postoperative complications.
RESULTS
Eight patients were identified, seven with soft tissue sarcoma and one with bone sarcoma. Patients had either localized disease with a primary thoracic sarcoma, sarcoma recurrent to the thorax, or de novo metastatic disease. All patients underwent resection of their pleural-based sarcoma by an experienced cardiothoracic surgeon, and some patients had pre or postoperative treatment. The perioperative morbidity was comparable with previously published reports of EPP performed in mesothelioma patients. At median follow-up of 22.5 months, median EFS was 6.0 months and OS was 20.7 months. Six patients (75%) had disease recurrence; five (62.5%) died of progressive disease. Two patients (25%) had not recurred: one died of a radiation-related esophageal rupture, and one was alive with no evidence of disease at 37.0 months. Characteristics of those with the longest EFS included low-grade histology and achieving a metabolic response to preoperative chemotherapy.
CONCLUSIONS
In adults with pleural-based sarcoma, EPP is rarely curative but appears to be a feasible salvage procedure when performed at specialized centers. Patient selection is critical with strong consideration given to multimodal therapy to optimize patient outcomes. In the absence of a confirmed response to neoadjuvant treatment, long term survival is poor and EPP should not be recommended.
Topics: Adult; Humans; Child; Pneumonectomy; Pleural Neoplasms; Neoplasm Recurrence, Local; Mesothelioma; Sarcoma
PubMed: 38627902
DOI: 10.1002/cnr2.2065 -
European Respiratory Review : An... Dec 2021Malignant pleural mesothelioma (MPM) is characterised by late-stage diagnosis and poor prognosis. Currently, no screening tool is advocated and diagnosis is based on... (Meta-Analysis)
Meta-Analysis Review
Malignant pleural mesothelioma (MPM) is characterised by late-stage diagnosis and poor prognosis. Currently, no screening tool is advocated and diagnosis is based on invasive techniques, which are not well tolerated. Non-invasive diagnostic biomarkers have shown potential and could have a huge clinical benefit. However, despite extensive research, there is no consensus yet on their clinical use, with many articles reporting contradicting results, limiting their clinical implementation. The aim of this systematic review is therefore to explore the different semi- and non-invasive diagnostic markers in several human matrices and identify those that might clinically be relevant. A total of 100 articles were selected through Web of Science and PubMed, with 56 articles included in the quantitative analysis. Although many studies have reported on the diagnostic accuracy of MPM biomarkers such as serum mesothelin and high-mobility group box protein 1 and plasma fibulin-3, none have resulted in a validated test for early detection. Future research should focus on external validation, combinations into biomarker panels, the inclusion of early stage MPM patients and a combination of different biomarker matrices, as well as new markers.
Topics: Biomarkers, Tumor; Humans; Lung Neoplasms; Mesothelioma; Mesothelioma, Malignant; Pleural Neoplasms; Prognosis
PubMed: 34789461
DOI: 10.1183/16000617.0057-2021 -
Thoracic Cancer Dec 2020Treatment of malignant pleural mesothelioma (MPM) represents a major challenge for oncologists. Multimodality treatment, which generally involves induction chemotherapy,...
BACKGROUND
Treatment of malignant pleural mesothelioma (MPM) represents a major challenge for oncologists. Multimodality treatment, which generally involves induction chemotherapy, surgery and radiotherapy have recently shown promising results. The aim of this study was to evaluate the locoregional control and toxicity of intensity modulated radiotherapy (IMRT) after pleurectomy and decortication (P/D) as part of trimodality therapy for patients with locally advanced MPM.
METHODS
We prospectively analyzed data from 20 patients with MPM treated at a single tertiary-care institution. Initially every patient received induction chemotherapy with platinum-based chemotherapy. After chemotherapy, patients without progression underwent P/D, and if feasible, hemi-thoracic IMRT was administered at a planned dose of 50.4-54 Gy in 28-30 fractions and treated with 9-11 noncoplanar fields.
RESULTS
A total of 15 of the 20 enrolled patients underwent P/D followed by IMRT to the hemi-thoracic cavity. The median total radiotherapy dose was 48.7 Gy (23.4-54 Gy). Radiation pneumonitis (RP) developed in nine patients (60%), and of these, two patients (13.3%) experienced G3 or G4 RP. The estimated locoregional-relapse-free survival at two years was 75.9%, and the main pattern of recurrence was distant (72.7%). For the entire cohort median follow-up was 22.7 months, median progression-free survival was 18.9 months and median overall survival 23.6 months.
CONCLUSIONS
Platinum-based chemotherapy followed by lung-sparing surgery (P/D) and IMRT is a feasible and safe treatment modality that yields acceptable locoregional control in patients with locally advanced MPM; however, these results should be corroborated in larger studies.
Topics: Aged; Aged, 80 and over; Female; Humans; Male; Mesothelioma, Malignant; Middle Aged; Pleural Neoplasms; Prospective Studies; Radiotherapy, Intensity-Modulated
PubMed: 33030313
DOI: 10.1111/1759-7714.13668 -
European Respiratory Review : An... Mar 2023Despite the progress in outcomes seen with immunotherapy in various malignancies, including nonsmall cell lung cancer, the benefits are less in small cell lung cancer,... (Review)
Review
Despite the progress in outcomes seen with immunotherapy in various malignancies, including nonsmall cell lung cancer, the benefits are less in small cell lung cancer, malignant pleural mesothelioma and thymic epithelial tumours. New effective treatment options are needed, guided more in-depth insights into the pathophysiology of these rare malignancies. This review comprehensively presents an overview of the clinical presentation, diagnostic tools, staging systems, pathophysiology and treatment options for these rare thoracic cancers. In addition, opportunities for further improvement of therapies are discussed.
Topics: Humans; Mesothelioma, Malignant; Small Cell Lung Carcinoma; Mesothelioma; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Pleural Neoplasms; Neoplasms, Glandular and Epithelial
PubMed: 36754434
DOI: 10.1183/16000617.0174-2022 -
International Journal of Molecular... Aug 2021Malignant Pleural Mesothelioma (MPM) is a rare and aggressive neoplasm of the pleural mesothelium, mainly associated with asbestos exposure and still lacking effective... (Review)
Review
Malignant Pleural Mesothelioma (MPM) is a rare and aggressive neoplasm of the pleural mesothelium, mainly associated with asbestos exposure and still lacking effective therapies. Modern targeted biological strategies that have revolutionized the therapy of other solid tumors have not had success so far in the MPM. Combination immunotherapy might achieve better results over chemotherapy alone, but there is still a need for more effective therapeutic approaches. Based on the peculiar disease features of MPM, several strategies for local therapeutic delivery have been developed over the past years. The common rationale of these approaches is: (i) to reduce the risk of drug inactivation before reaching the target tumor cells; (ii) to increase the concentration of active drugs in the tumor micro-environment and their bioavailability; (iii) to reduce toxic effects on normal, non-transformed cells, because of much lower drug doses than those used for systemic chemotherapy. The complex interactions between drugs and the local immune-inflammatory micro-environment modulate the subsequent clinical response. In this perspective, the main interest is currently addressed to the development of local drug delivery platforms, both cell therapy and engineered nanotools. We here propose a review aimed at deep investigation of the biologic effects of the current local therapies for MPM, including cell therapies, and the mechanisms of interaction with the tumor micro-environment.
Topics: Combined Modality Therapy; Drug Delivery Systems; Humans; Immunotherapy; Mesothelioma; Mesothelioma, Malignant; Pleural Neoplasms; Soft Tissue Neoplasms; Tumor Microenvironment
PubMed: 34445720
DOI: 10.3390/ijms22169014 -
Thoracic Cancer Aug 2023Pleural mesothelioma (PM) is a relatively rare malignancy with limited treatment options and dismal prognosis. We have previously found elevated FGF18 expression in PM...
BACKGROUND
Pleural mesothelioma (PM) is a relatively rare malignancy with limited treatment options and dismal prognosis. We have previously found elevated FGF18 expression in PM tissue specimens compared with normal mesothelium. The objective of the current study was to further explore the role of FGF18 in PM and evaluate its suitability as a circulating biomarker.
METHODS
FGF18 mRNA expression was analyzed by real-time PCR in cell lines and in silico in datasets from the Cancer Genome Atlas (TCGA). Cell lines overexpressing FGF18 were generated by retroviral transduction and cell behavior was investigated by clonogenic growth and transwell assays. Plasma was collected from 40 PM patients, six patients with pleural fibrosis, and 40 healthy controls. Circulating FGF18 was measured by ELISA and correlated to clinicopathological parameters.
RESULTS
FGF18 showed high mRNA expression in PM and PM-derived cell lines. PM patients with high FGF18 mRNA expression showed a trend toward longer overall survival (OS) in the TCGA dataset. In PM cells with low endogenous FGF18 expression, forced overexpression of FGF18 resulted in reduced growth but increased migration. Surprisingly, despite the high FGF18 mRNA levels observed in PM, circulating FGF18 protein was significantly lower in PM patients and patients with pleural fibrosis than in healthy controls. No significant association of circulating FGF18 with OS or other disease parameters of PM patients was observed.
CONCLUSIONS
FGF18 is not a prognostic biomarker in PM. Its role in PM tumor biology and the clinical significance of decreased plasma FGF18 in PM patients warrant further investigation.
Topics: Humans; Fibrosis; Lung Neoplasms; Mesothelioma; Mesothelioma, Malignant; Pleural Neoplasms; Prognosis; RNA, Messenger
PubMed: 37340889
DOI: 10.1111/1759-7714.15004 -
Clinical & Translational Oncology :... May 2021Mesothelioma is a rare and aggressive tumour with dismal prognosis arising in the pleura and associated with asbestos exposure. Its incidence is on the rise worldwide.... (Review)
Review
Mesothelioma is a rare and aggressive tumour with dismal prognosis arising in the pleura and associated with asbestos exposure. Its incidence is on the rise worldwide. In selected patients with early-stage MPM, a maximal surgical cytoreduction in combination with additional antitumour treatment may be considered in selected patients assessed by a multidisciplinary tumor board. In patients with unresectable or advanced MPM, chemotherapy with platinum plus pemetrexed is the standard of care. Currently, no standard salvage therapy has been approved yet, but second-line chemotherapy with vinorelbine or gemcitabine is commonly used. Novel therapeutic approaches based on dual immunotherapy or chemotherapy plus immunotherapy demonstrated promising survival benefit and will probably be incorporated in the future.
Topics: Antineoplastic Agents; Asbestos; Carcinogens; Combined Modality Therapy; Cytoreduction Surgical Procedures; Deoxycytidine; Genetic Testing; High-Throughput Nucleotide Sequencing; Humans; Immunotherapy; Medical Oncology; Mesothelioma, Malignant; Neoplasm Staging; Pemetrexed; Platinum Compounds; Pleural Neoplasms; Radiotherapy; Societies, Medical; Spain; Vinorelbine; Gemcitabine
PubMed: 33538989
DOI: 10.1007/s12094-020-02532-2 -
Expert Review of Respiratory Medicine Oct 2015Malignant mesothelioma is an aggressive cancer whose pathogenesis is causally linked to occupational exposure to asbestos. Familial clusters of mesotheliomas have been... (Review)
Review
Malignant mesothelioma is an aggressive cancer whose pathogenesis is causally linked to occupational exposure to asbestos. Familial clusters of mesotheliomas have been observed in settings of genetic predisposition. Mesothelioma incidence is anticipated to increase worldwide in the next two decades. Novel treatments are needed, as current treatment modalities may improve the quality of life, but have shown modest effects in improving overall survival. Increasing knowledge on the molecular characteristics of mesothelioma has led to the development of novel potential therapeutic strategies, including: molecular targeted approaches, that is the inhibition of vascular endothelial growth factor with bevacizumab; immunotherapy with chimeric monoclonal antibody, immunotoxin, antibody drug conjugate, vaccine and viruses; inhibition of asbestos-induced inflammation, that is aspirin inhibition of HMGB1 activity may decrease or delay mesothelioma onset and/or growth. We elaborate on the rationale behind new therapeutic strategies, and summarize available preclinical and clinical results, as well as efforts still ongoing.
Topics: Humans; Immunotherapy; Lung Neoplasms; Mesothelioma; Mesothelioma, Malignant; Molecular Targeted Therapy; Peritoneal Neoplasms; Pleural Neoplasms
PubMed: 26308799
DOI: 10.1586/17476348.2015.1081066