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Journal of Proteomics Jun 2024To identify protein biomarkers capable of early prediction regarding the distinguishing malignant pleural effusion (MPE) from benign pleural effusion (BPE) in patients...
To identify protein biomarkers capable of early prediction regarding the distinguishing malignant pleural effusion (MPE) from benign pleural effusion (BPE) in patients with lung disease. A four-dimensional data independent acquisition (4D-DIA) proteomic was performed to determine the differentially expressed proteins in samples from 20 lung adenocarcinoma MPE and 30 BPE. The significantly differential expressed proteins were selected for Gene Ontology (GO) enrichment and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway analysis. Protein biomarkers with high capability to discriminate MPE from BPE patients were identified by Random Forest (RF) algorithm prediction model, whose diagnostic and prognostic efficacy in primary tumors were further explored in public datasets, and were validated by ELISA experiment. 50 important proteins (30 up-regulated and 20 down-regulated) were selected out as potential markers to distinguish the MPE from BPE group. GO analysis revealed that those proteins involving the most important cell component is extracellular space. KEGG analysis identified the involvement of cellular adhesion molecules pathway. Furthermore, the Area Under Curve (AUC) of these proteins were ranged from 0.717 to 1.000,with excellent diagnostic properties to distinguish the MPE. Finally, significant survival and gene and protein expression analysis demonstrated BPIFB1, DPP4, HPRT1 and ABI3BP had high discriminating values. SIGNIFICANCE: We performed a 4D-DIA proteomics to determine the differentially expressed proteins in pleural effusion samples from MPE and BPE. Some potential protein biomarkers were identified to distinguish the MPE from BPE patients., which may provide helpful diagnostic and therapeutic insights for lung cancer. This is significant because the median survival time of patients with MPE is usually 4-12 months, thus, it is particularly important to diagnose MPE early to start treatments promptly. The most common causes of MPE are lung cancers, while pneumonia and tuberculosis are the main causes of BPE. If more diagnostic markers could be identified periodically, there would be an important significance to clinical diagnose and treatment with drugs in lung cancer patients.
Topics: Humans; Pleural Effusion, Malignant; Biomarkers, Tumor; Proteomics; Female; Male; Lung Neoplasms; Pleural Effusion; Diagnosis, Differential; Middle Aged; Neoplasm Proteins; Aged; Adenocarcinoma of Lung
PubMed: 38768894
DOI: 10.1016/j.jprot.2024.105201 -
Pharmacological Research Jun 2024
Topics: Humans; Mesothelin; Immunotherapy, Adoptive; Mesothelioma, Malignant; Receptors, Chimeric Antigen; GPI-Linked Proteins; Animals; Lung Neoplasms
PubMed: 38768670
DOI: 10.1016/j.phrs.2024.107220 -
BMJ Open May 2024Extrapleural pneumonectomy (EPP) and extended pleurectomy/decortication (ePD) are surgical cytoreductive techniques aimed at achieving macroscopic resection in malignant... (Review)
Review
INTRODUCTION
Extrapleural pneumonectomy (EPP) and extended pleurectomy/decortication (ePD) are surgical cytoreductive techniques aimed at achieving macroscopic resection in malignant pleural tumours such as pleural mesothelioma, non-mesothelioma pleural malignancies such as thymoma and sarcoma, and rarely for pleural tuberculosis, in a more limited fashion. Despite extensive studies on both surgical techniques and consequences, a significant knowledge gap remains regarding how best to approach the perioperative anaesthesia challenges for EPP and ePD.It is unknown if the risk stratification processes for such surgeries are standardised or what types of functional and dynamic cardiac and pulmonary tests are employed preoperatively to assist in the perioperative risk stratification. Further, it is unknown whether the types of anaesthesia and analgesia techniques employed, and the types of haemodynamic monitoring tools used, impact on outcomes. It is also unknown whether individualised haemodynamic protocols are used to guide the rational use of fluids, vasoactive drugs and inotropes.Finally, there is a dearth of evidence regarding how best to monitor these patients postoperatively or what the most effective enhanced recovery protocols are to best mitigate postoperative complications and accelerate hospital discharge. To increase our knowledge of the perioperative and anaesthetic treatment for patients undergoing EPP/ePD, this scoping review attempts to synthesise the literature and identify these knowledge gaps.
METHODS AND ANALYSIS
This scoping review will be conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis Extension for Scoping Review Protocols methodology. Electronic databases, OVID Medline, EMBASE and the Cochrane Library, will be systematically searched for relevant literature corresponding to EPP or ePD and perioperative or anaesthetic management. Data will be analysed and summarised descriptively and organised according to the three perioperative stages: preoperative, intraoperative and postoperative factors in clinical care.
ETHICS AND DISSEMINATION
Ethics approval was not required. The findings will be disseminated through professional networks, conference presentations and publications in scientific journals.
Topics: Humans; Pneumonectomy; Anesthesia; Pleura; Perioperative Care; Pleural Neoplasms; Postoperative Complications
PubMed: 38760041
DOI: 10.1136/bmjopen-2023-078125 -
BMJ Open May 2024Recruiting to randomised trials is often challenging particularly when the intervention arms are markedly different. The Mesothelioma and Radical Surgery 2 randomised... (Randomized Controlled Trial)
Randomized Controlled Trial
Strategies to address recruitment to a randomised trial of surgical and non-surgical treatment for cancer: results from a complex recruitment intervention within the Mesothelioma and Radical Surgery 2 (MARS 2) study.
OBJECTIVES
Recruiting to randomised trials is often challenging particularly when the intervention arms are markedly different. The Mesothelioma and Radical Surgery 2 randomised controlled trial (RCT) compared standard chemotherapy with or without (extended) pleurectomy decortication surgery for malignant pleural mesothelioma. Anticipating recruitment difficulties, a QuinteT Recruitment Intervention was embedded in the main trial phase to unearth and address barriers. The trial achieved recruitment to target with a 4-month COVID-19 pandemic-related extension. This paper presents the key recruitment challenges, and the strategies delivered to optimise recruitment and informed consent.
DESIGN
A multifaceted, flexible, mixed-method approach to investigate recruitment obstacles drawing on data from staff/patient interviews, audio recorded study recruitment consultations and screening logs. Key findings were translated into strategies targeting identified issues. Data collection, analysis, feedback and strategy implementation continued cyclically throughout the recruitment period.
SETTING
Secondary thoracic cancer care.
RESULTS
Respiratory physicians, oncologists, surgeons and nursing specialists supported the trial, but recruitment challenges were evident. The study had to fit within a framework of a thoracic cancer service considered overstretched where patients encountered multiple healthcare professionals and treatment views, all of which challenged recruitment. Clinician treatment biases, shaped in part by the wider clinical and research context alongside experience, adversely impacted several aspects of the recruitment process by restricting referrals for study consideration, impacting eligibility decisions, affecting the neutrality in which the study and treatment was presented and shaping patient treatment expectations and preferences. Individual and group recruiter feedback and training raised awareness of key equipoise issues, offered support and shared good practice to safeguard informed consent and optimise recruitment.
CONCLUSIONS
With bespoke support to overcome identified issues, recruitment to a challenging RCT of surgery versus no surgery in a thoracic cancer setting with a complex recruitment pathway and multiple health professional involvement is possible.
TRIAL REGISTRATION NUMBER
ISRCTN ISRCTN44351742, Clinical Trials.gov NCT02040272.
Topics: Humans; Patient Selection; Mesothelioma; COVID-19; Mesothelioma, Malignant; Pleural Neoplasms; Randomized Controlled Trials as Topic; Lung Neoplasms; SARS-CoV-2; Informed Consent; Female; Male
PubMed: 38760029
DOI: 10.1136/bmjopen-2023-079108 -
BMC Pulmonary Medicine May 2024Pleural fluid is one of the common complications of thoracic diseases, and tuberculous pleural effusion (TPE) is the most common cause of pleural effusion in TB-endemic...
BACKGROUND
Pleural fluid is one of the common complications of thoracic diseases, and tuberculous pleural effusion (TPE) is the most common cause of pleural effusion in TB-endemic areas and the most common type of exudative pleural effusion in China. In clinical practice, distinguishing TPE from pleural effusion caused by other reasons remains a relatively challenging issue. The objective of present study was to explore the clinical significance of the pleural fluid lactate dehydrogenase/adenosine deaminase ratio (pfLDH/pfADA) in the diagnosis of TPE.
METHODS
The clinical data of 618 patients with pleural effusion were retrospectively collected, and the patients were divided into 3 groups: the TPE group (412 patients), the parapneumonic pleural effusion (PPE) group (106 patients), and the malignant pleural effusion (MPE) group (100 patients). The differences in the ratios of pleural effusion-related and serology-related indicators were compared among the three groups, and receiver operating characteristic curves were drawn to analyze the sensitivity and specificity of the parameter ratios of different indicators for the diagnosis of TPE.
RESULTS
The median serum ADA level was higher in the TPE group (13 U/L) than in the PPE group (10 U/L, P < 0.01) and MPE group (10 U/L, P < 0.001). The median pfADA level in the TPE group was 41 (32, 52) U/L; it was lowest in the MPE group at 9 (7, 12) U/L and highest in the PPE group at 43 (23, 145) U/L. The pfLDH level in the PPE group was 2542 (1109, 6219) U/L, which was significantly higher than that in the TPE group 449 (293, 664) U/L. In the differential diagnosis between TPE and non-TPE, the AUC of pfLDH/pfADA for diagnosing TPE was the highest at 0.946 (0.925, 0.966), with an optimal cutoff value of 23.20, sensitivity of 93.9%, specificity of 87.0%, and Youden index of 0.809. In the differential diagnosis of TPE and PPE, the AUC of pfLDH/pfADA was the highest at 0.964 (0.939, 0.989), with an optimal cutoff value of 24.32, sensitivity of 94.6%, and specificity of 94.4%; this indicated significantly better diagnostic efficacy than that of the single index of pfLDH. In the differential diagnosis between TPE and MPE, the AUC of pfLDH/pfADA was 0.926 (0.896, 0.956), with a sensitivity of 93.4% and specificity of 80.0%; this was not significantly different from the diagnostic efficacy of pfADA.
CONCLUSIONS
Compared with single biomarkers, pfLDH/pfADA has higher diagnostic value for TPE and can identify patients with TPE early, easily, and economically.
Topics: Humans; Adenosine Deaminase; Male; Female; Retrospective Studies; Middle Aged; Pleural Effusion; L-Lactate Dehydrogenase; Tuberculosis, Pleural; Adult; Aged; Sensitivity and Specificity; ROC Curve; China; Diagnosis, Differential; Pleural Effusion, Malignant; Biomarkers; Clinical Relevance
PubMed: 38750432
DOI: 10.1186/s12890-024-03055-0 -
Jornal Brasileiro de Pneumologia :... 2024To review the pathological diagnosis of possible cases and/or hidden cases of malignant mesothelioma (MM) between 2000 and 2012 using the Hospital-Based Cancer Registry...
OBJECTIVE
To review the pathological diagnosis of possible cases and/or hidden cases of malignant mesothelioma (MM) between 2000 and 2012 using the Hospital-Based Cancer Registry database in the state of São Paulo, Brazil.
METHODS
Possible cases were retrieved by assessing the database. Inclusion criteria were being older than 30 years of age and having ICD-O-3 topography and morphology codes related to MM. A board of expert pathologists reviewed the pathology reports and requested paraffin blocks in cases that demanded revision. After staining with calretinin, D2-40, WT-1 (as positive MM markers) and Ber-EP4 and MOC31 (as negative MM markers), cases were divided and studied independently by a pair of pathologists to confirm or discard the diagnosis of MM.
RESULTS
Our sample comprised 482 cases from 25 hospitals, and 130 needed further histological revision. We received 73 paraffin blocks with adequate material. After board analysis, there were 9 cases with a definitive diagnosis of MM, improving the diagnostic rate in 12%. Two cases of previously diagnosed MM were discarded by review.
CONCLUSIONS
Our results confirm that part of MM underdiagnosis and underreporting in Brazil is due to incomplete or mistaken pathological diagnosis.
Topics: Humans; Brazil; Mesothelioma; Mesothelioma, Malignant; Registries; Male; Female; Middle Aged; Aged; Lung Neoplasms; Adult; Aged, 80 and over; Biomarkers, Tumor; Pleural Neoplasms
PubMed: 38747814
DOI: 10.36416/1806-3756/e20230343 -
Multimedia Manual of Cardiothoracic... May 2024The current treatment for mesothelioma, in selected cases, consists of extended pleurodecortication and intrathoracic hyperthermic chemotherapy. This technique is...
The current treatment for mesothelioma, in selected cases, consists of extended pleurodecortication and intrathoracic hyperthermic chemotherapy. This technique is laborious and detailed and must be followed step by step to achieve good results. We present the case of a patient with epithelioid mesothelioma meeting surgical criteria who underwent the mentioned technique, experiencing an adequate postoperative period and an early discharge. This experience demonstrates that the technique is safe when performed in centres with experience and the means to address this complex pathology.
Topics: Humans; Pleural Neoplasms; Mesothelioma, Malignant; Hyperthermia, Induced; Combined Modality Therapy; Mesothelioma; Male; Lung Neoplasms; Middle Aged
PubMed: 38747474
DOI: 10.1510/mmcts.2024.007 -
The Lancet. Respiratory Medicine Jun 2024Extended pleurectomy decortication for complete macroscopic resection for pleural mesothelioma has never been evaluated in a randomised trial. The aim of this study was... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
BACKGROUND
Extended pleurectomy decortication for complete macroscopic resection for pleural mesothelioma has never been evaluated in a randomised trial. The aim of this study was to compare outcomes after extended pleurectomy decortication plus chemotherapy versus chemotherapy alone.
METHODS
MARS 2 was a phase 3, national, multicentre, open-label, parallel two-group, pragmatic, superiority randomised controlled trial conducted in the UK. The trial took place across 26 hospitals (21 recruiting only, one surgical only, and four recruiting and surgical). Following two cycles of chemotherapy, eligible participants with pleural mesothelioma were randomly assigned (1:1) to surgery and chemotherapy or chemotherapy alone using a secure web-based system. Individuals aged 16 years or older with resectable pleural mesothelioma and adequate organ and lung function were eligible for inclusion. Participants in the chemotherapy only group received two to four further cycles of chemotherapy, and participants in the surgery and chemotherapy group received pleurectomy decortication or extended pleurectomy decortication, followed by two to four further cycles of chemotherapy. It was not possible to mask allocation because the intervention was a major surgical procedure. The primary outcome was overall survival, defined as time from randomisation to death from any cause. Analyses were done on the intention-to-treat population for all outcomes, unless specified. This study is registered with ClinicalTrials.gov, NCT02040272, and is closed to new participants.
FINDINGS
Between June 19, 2015, and Jan 21, 2021, of 1030 assessed for eligibility, 335 participants were randomly assigned (169 to surgery and chemotherapy, and 166 to chemotherapy alone). 291 (87%) participants were men and 44 (13%) women, and 288 (86%) were diagnosed with epithelioid mesothelioma. At a median follow-up of 22·4 months (IQR 11·3-30·8), median survival was shorter in the surgery and chemotherapy group (19·3 months [IQR 10·0-33·7]) than in the chemotherapy alone group (24·8 months [IQR 12·6-37·4]), and the difference in restricted mean survival time at 2 years was -1·9 months (95% CI -3·4 to -0·3, p=0·019). There were 318 serious adverse events (grade ≥3) in the surgery group and 169 in the chemotherapy group (incidence rate ratio 3·6 [95% CI 2·3 to 5·5], p<0·0001), with increased incidence of cardiac (30 vs 12; 3·01 [1·13 to 8·02]) and respiratory (84 vs 34; 2·62 [1·58 to 4·33]) disorders, infection (124 vs 53; 2·13 [1·36 to 3·33]), and additional surgical or medical procedures (15 vs eight; 2·41 [1·04 to 5·57]) in the surgery group.
INTERPRETATION
Extended pleurectomy decortication was associated with worse survival to 2 years, and more serious adverse events for individuals with resectable pleural mesothelioma, compared with chemotherapy alone.
FUNDING
National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (15/188/31), Cancer Research UK Feasibility Studies Project Grant (A15895).
Topics: Humans; Female; Male; Pleural Neoplasms; Middle Aged; Aged; Mesothelioma; Treatment Outcome; United Kingdom; Pleura; Mesothelioma, Malignant; Combined Modality Therapy; Adult; Antineoplastic Combined Chemotherapy Protocols; Lung Neoplasms
PubMed: 38740044
DOI: 10.1016/S2213-2600(24)00119-X -
Radiology Case Reports Aug 2024Nodular soft tissue pleural thickening on imaging is highly suggestive of malignancy, of which pleural malignant mesothelioma and metastatic disease are differentials....
Nodular soft tissue pleural thickening on imaging is highly suggestive of malignancy, of which pleural malignant mesothelioma and metastatic disease are differentials. We present the case of a 71-year-old male who presented with acute worsening of shortness of breath associated with a recurrent left pleural effusion post-pleurocentesis. He was an ex-smoker with previous asbestos exposure. Computed tomography performed demonstrated left-sided pleural thickening in the hemithorax and hemidiaphragm with complex pleural effusion. F-2-deoxy-d-glucose whole body PET scan revealed extensive uptake throughout the left hemithorax in multiple pleural masses. The imaging findings and clinical case were typical of malignant mesothelioma. However, histopathology results revealed small cell lung cancer. We need to be cognisant of this atypical presentation of a common disease entity. Even when all clinical and imaging findings point towards a certain diagnosis, histopathological assessment cannot be ignored.
PubMed: 38737188
DOI: 10.1016/j.radcr.2024.04.011 -
PloS One 2024With recent advances in magnetic resonance imaging (MRI) technology, the practical role of lung MRI is expanding despite the inherent challenges of the thorax. The...
BACKGROUND
With recent advances in magnetic resonance imaging (MRI) technology, the practical role of lung MRI is expanding despite the inherent challenges of the thorax. The purpose of our study was to evaluate the current status of the concurrent dephasing and excitation (CODE) ultrashort echo-time sequence and the T1-weighted volumetric interpolated breath-hold examination (VIBE) sequence in the evaluation of thoracic disease by comparing it with the gold standard computed tomography (CT).
METHODS
Twenty-four patients with lung cancer and mediastinal masses underwent both CT and MRI including T1-weighted VIBE and CODE. For CODE images, data were acquired in free breathing and end-expiratory images were reconstructed using retrospective respiratory gating. All images were evaluated through qualitative and quantitative approaches regarding various anatomical structures and lesions (nodule, mediastinal mass, emphysema, reticulation, honeycombing, bronchiectasis, pleural plaque and lymphadenopathy) inside the thorax in terms of diagnostic performance in making specific decisions.
RESULTS
Depiction of the lung parenchyma, mediastinal and pleural lesion was not significant different among the three modalities (p > 0.05). Intra-tumoral and peritumoral features of lung nodules were not significant different in the CT, VIBE or CODE images (p > 0.05). However, VIBE and CODE had significantly lower image quality and poorer depiction of airway, great vessels, and emphysema compared to CT (p < 0.05). Image quality of central airways and depiction of bronchi were significantly better in CODE than in VIBE (p < 0.001 and p = 0.005). In contrast, the depiction of the vasculature was better for VIBE than CODE images (p = 0.003). The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were significant greater in VIBE than CODE except for SNRlung and SNRnodule (p < 0.05).
CONCLUSIONS
Our study showed the potential of CODE and VIBE sequences in the evaluation of localized thoracic abnormalities including solid pulmonary nodules.
Topics: Humans; Female; Male; Middle Aged; Lung Neoplasms; Aged; Tomography, X-Ray Computed; Magnetic Resonance Imaging; Imaging, Three-Dimensional; Adult; Lung; Retrospective Studies; Breath Holding
PubMed: 38722966
DOI: 10.1371/journal.pone.0296696