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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 -
Portuguese Journal of Cardiac Thoracic... Jan 2022Solitary fibrous tumor of the pleura (SFTP) is a rare neoplasm that accounts for less than 5% of all pleural tumors. We present the case of a 73-year-old man with a...
Solitary fibrous tumor of the pleura (SFTP) is a rare neoplasm that accounts for less than 5% of all pleural tumors. We present the case of a 73-year-old man with a history of recurrent episodes of severe hypoglycemia secondary to a large malignant SFTP. This paraneoplastic manifestation of SFTP occurs in less than 5% of cases and is referred to as Doege-Potter syndrome. Although rare, this is an important and reversible cause of hypoglycemia, which is resolved by complete surgical resection of the tumor. We describe the pathogenesis, diagnosis, and treatment of Doege-Potter syndrome. Key imaging findings and pathologic correlation are shown.
Topics: Aged; Congenital Abnormalities; Humans; Kidney; Kidney Diseases; Male; Pleural Neoplasms; Solitary Fibrous Tumor, Pleural
PubMed: 35334174
DOI: 10.48729/pjctvs.225 -
Respiration; International Review of... 2021Lung-sparing cytoreductive surgery by extended pleurectomy and decortication (EPD) in combination with hyperthermic intrathoracic chemoperfusion (HITOC) forms a...
BACKGROUND
Lung-sparing cytoreductive surgery by extended pleurectomy and decortication (EPD) in combination with hyperthermic intrathoracic chemoperfusion (HITOC) forms a promising treatment strategy for malignant pleural mesothelioma and recurrent pleural thymic malignancies.
OBJECTIVES
The objective of this study was to scrutinize the surgical procedure and perioperative patient management with emphasis on perioperative morbidity and local tumor control.
METHODS
In 2014, a standardized EPD and HITOC procedure was implemented at the Thoraxklinik Heidelberg. This retrospective analysis included clinical data of consecutive patients with pleural mesothelioma and pleural metastasized malignancies treated by EPD and HITOC. The surgical procedure, perioperative management, lung function data, and progression-free survival (PFS) were analyzed.
RESULTS
In the time range between April 2, 2014 and July 2018, 76 patients with pleural malignancies have been treated with EPD and HITOC, and were analyzed retrospectively. It included 61 patients with pleural mesothelioma and 15 patients with pleural metastases of thymic malignancies (12), non-small cell lung cancer (1), colorectal carcinoma (1), and sarcoma (1). Perioperative morbidity following EPD and HITOC treatments represented 23.7% of overall malignancies, while 30- and 90-day mortality were 0 and 1.3%, respectively. Median PFS lasted 18.4 months for mesothelioma and 72.2 months for thymic malignancies.
CONCLUSION
Combining EPD with HITOC can be performed in patients with either pleural mesothelioma or pleural metastases resulting in low perioperative morbidity and mortality as well as remarkable local tumor control.
Topics: Carcinoma, Non-Small-Cell Lung; Combined Modality Therapy; Cytoreduction Surgical Procedures; Humans; Hyperthermia, Induced; Lung Neoplasms; Mesothelioma; Mesothelioma, Malignant; Neoplasm Recurrence, Local; Pleural Neoplasms; Retrospective Studies; Thoracic Surgery; Thymus Neoplasms; Treatment Outcome
PubMed: 34384085
DOI: 10.1159/000517334 -
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 -
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 -
The Annals of Thoracic Surgery Nov 2016In patients with thymic neoplasms, the pleural space is a frequent site of either synchronous or metachronous tumor dissemination after surgical resection. The objective...
BACKGROUND
In patients with thymic neoplasms, the pleural space is a frequent site of either synchronous or metachronous tumor dissemination after surgical resection. The objective of this study was to identify factors that predict pleural dissemination, which would allow for better surgical planning and consideration of novel adjuvant or surveillance strategies.
METHODS
A retrospective review of a prospective database (2000 to 2014) was performed to identify patients with thymic tumors (excluding neuroendocrine). Demographic, clinical, and pathologic data were reviewed. Multivariable Cox regression analysis was performed to determine independent predictors of pleural implants (either occult synchronous or metachronous). Univariate predictors (p < 0.20) were selected for inclusion in a multivariable model. Receiver operating characteristic (ROC) curve was used to assess the effect and cutoff value of tumor size on the incidence of pleural metastasis.
RESULTS
One hundred sixty-two patients with thymic tumors were identified. Pleural deposits were incidentally identified intraoperatively in 4 patients (2.5%) and developed during follow-up in 15 patients (10%), with a median follow-up of 34 months (interquartile range, 12 to 71). Univariate predictors of pleural metastasis were macroscopic capsular/organ invasion, preoperative core/surgical biopsy, induction therapy, pathologic tumor size, and World Health Organization type B3/C. In the multivariable model, core/surgical biopsy (hazard ratio [HR] 9.45, p = 0.002), macroscopic capsular invasion (HR 10.18, p = 0.008), and larger tumor size (HR 1.34, p = 0.044) were found to be independent predictors of pleural metastasis. The relation between the pathologic tumor size and development of pleural metastasis was further investigated with the ROC curve (area under the curve 0.78, p < 0.001), and the cutoff tumor size that gave the best combined sensitivity and specificity was 6.5 cm. Overall survival of patients with pleural implants was 88% and 50% at 5 and 10 years, respectively. Five- and 10- year disease-free survival for the whole cohort was 80% and 30%, respectively.
CONCLUSIONS
Development of pleural metastasis is predictable. Pathologic tumor size, an independent predictor of pleural implants, can be assessed intraoperatively. Because preoperative core needle biopsy is also an independent predictor of pleural dissemination, its use and execution should be carefully considered. Pleural exploration at the index operation should be considered in high-risk patients. Further studies are needed to confirm these findings and to assess the role of novel therapeutic strategies in reducing pleural disease.
Topics: Adult; Aged; Biopsy, Needle; Disease-Free Survival; Female; Follow-Up Studies; Forecasting; Humans; Male; Middle Aged; Neoplasm Invasiveness; Neoplasm Staging; New York; Pleura; Pleural Neoplasms; Prognosis; Retrospective Studies; Risk Factors; Survival Rate; Thymectomy; Thymus Neoplasms; Tumor Burden
PubMed: 27324527
DOI: 10.1016/j.athoracsur.2016.04.026 -
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 -
Academic Radiology Mar 2015To evaluate the clinical utility of three-dimensional (3D) computed tomography (CT) for predicting pleural invasion by peripheral lung cancer.
RATIONALE AND OBJECTIVES
To evaluate the clinical utility of three-dimensional (3D) computed tomography (CT) for predicting pleural invasion by peripheral lung cancer.
MATERIALS AND METHODS
CT findings (tumor size, vertical diameter, length and area of the interface between tumor and the pleura, ratios of length and area [Rarea] of interface between tumor and the pleura to tumor size, angle between the tumor and adjacent pleura, presence or absence of pleural thickening, and originally developed 3D pleural patterns) in 201 consecutive patients with lung cancer of ≤3 cm in contact with pleural surface were correlated with pathologic findings. Logistic modeling was used for determining the significant factors for prediction of pleural invasion, and receiver operating characteristic (ROC) curves were used for investigating diagnostic capability of significant factors, resulting in a recommendation to the optimal criteria for predicting pleural invasion and to the optimal threshold for differentiating parietal from visceral invasion.
RESULTS
Sixty-one (30%) of the 201 patients had pathologically verified pleural invasion. Logistic modeling revealed that the 3D pleural pattern was the only significant factor (P < .001; relative risk of 7.34). Among every combination of the 3D patterns, skirt-like pattern showed the highest accuracy of 77% for predicting pleural invasion. In differentiating parietal from visceral pleural invasion, ROC analysis revealed that Rarea was optimal for differentiating parietal from visceral pleural invasion, and the highest accuracy of 77% was obtained with a cut-off value of 13.4 for this criterion.
CONCLUSIONS
Computer-aided 3D CT analysis of the pleura was useful for predicting pleural invasion.
Topics: Aged; Contrast Media; Female; Humans; Imaging, Three-Dimensional; Lung Neoplasms; Male; Middle Aged; Neoplasm Invasiveness; Observer Variation; Pleura; Pleural Neoplasms; Predictive Value of Tests; ROC Curve; Radiographic Image Enhancement; Reproducibility of Results; Tomography, X-Ray Computed
PubMed: 25542401
DOI: 10.1016/j.acra.2014.10.002