-
Pharmacogenomics Jul 2018
Topics: Biomarkers, Tumor; Drug Resistance, Neoplasm; Humans; Lung Neoplasms; Mesothelioma; Mesothelioma, Malignant; Pemetrexed; Pleural Neoplasms; Proton-Coupled Folate Transporter
PubMed: 29916298
DOI: 10.2217/pgs-2018-0071 -
Chest Sep 2009Although the insulating properties of asbestos have been known for millennia, the link between asbestos exposure and mesothelioma was not recognized until 1960, when it... (Review)
Review
Although the insulating properties of asbestos have been known for millennia, the link between asbestos exposure and mesothelioma was not recognized until 1960, when it was first described in South African asbestos miners. The incidence of mesothelioma parallels asbestos usage with a latency of 20 to 40+ years; thus, patient numbers are declining in the United States but rising in the developing world. Radiation, genetics, and possibly simian virus 40 are less common causes. Diagnosis can be challenging, since the results of pleural fluid cytology testing are often negative despite repeated sampling. No staging system adequately predicts prognosis in the unresected patient. Newly described biomarkers, including soluble mesothelin-related peptide, megakaryocyte potentiation factor, and osteopontin, may predict which asbestos-exposed individuals will develop mesothelioma, and may prove useful in assessing response to treatment. Since surgery cannot eradicate all residual microscopic disease, a multimodality approach is encouraged. Metaanalysis suggests that pleurectomy/decortication may achieve outcomes similar to those of extrapleural penumonectomy. The standard first-line chemotherapy for unresectable disease is pemetrexed plus cisplatin. This combination improves response, survival, time to progression, pulmonary function, and disease-related symptoms. Carboplatin is often substituted, with similar results. Other active agents include raltitrexed, gemcitabine, and vinorelbine. Novel agents in clinical trials include inhibitors of the epidermal growth factor receptor, vascular endothelial growth factor, mesothelin, and histone deacetylases. Although disappointing results of early trials did not confirm promising preclinical data, recent studies have suggested that some novel agents may be effective. As we learn more about mesothelioma biology, molecularly targeted agents may become treatment options.
Topics: Biomarkers, Tumor; Humans; Mesothelioma; Neoplasm Staging; Pleural Neoplasms; Prognosis
PubMed: 19736192
DOI: 10.1378/chest.08-2665 -
Journal of Thoracic Imaging May 2006Malignant pleural mesothelioma (MPM) is an uncommon neoplasm arising from mesothelial cells of the pleura. The prognosis is poor with a median survival of 8 to 18 months... (Review)
Review
Malignant pleural mesothelioma (MPM) is an uncommon neoplasm arising from mesothelial cells of the pleura. The prognosis is poor with a median survival of 8 to 18 months after diagnosis. Multimodality regimens combining chemotherapy, radiotherapy, immunotherapy, and surgery are being used more frequently in patient management. Extrapleural pneumonectomy is the surgical treatment of choice in 10% to 15% of patients who present with resectable disease and is reported to prolong survival. Accurate staging is important to distinguish patients who are resectable from those requiring palliative therapy. Integrated computed tomography-positron emission tomography (CT-PET) increases the accuracy of overall staging in patients with MPM and significantly improves the selection of patients for curative surgical resection. Specifically, CT-PET detects more extensive disease involvement than that shown by other imaging modalities and is particularly useful in identifying occult distant metastases. This article reviews aspects of imaging performed in the initial staging of patients with MPM according to the International Mesothelioma Interest Group staging system and will emphasize the appropriate role of CT-PET imaging in determining the T, N, and M descriptors.
Topics: Combined Modality Therapy; Humans; Lung Neoplasms; Magnetic Resonance Imaging; Mesothelioma; Neoplasm Staging; Pleural Neoplasms; Positron-Emission Tomography; Sensitivity and Specificity; Tomography, X-Ray Computed
PubMed: 16770231
DOI: 10.1097/00005382-200605000-00006 -
Current Opinion in Pulmonary Medicine Jul 2008Mesothelioma is an aggressive malignancy of the pleura with poor survival. There will be approximately 3000 cases of mesothelioma in the United States annually.... (Review)
Review
PURPOSE OF REVIEW
Mesothelioma is an aggressive malignancy of the pleura with poor survival. There will be approximately 3000 cases of mesothelioma in the United States annually. Multimodality treatment including neoadjuvant chemotherapy in selected individuals followed by extrapleural pneumonectomy and radiation has been studied in recent trials for its effects on disease free and overall survival This review provides a general overview of malignant mesothelioma with a summary of the most significant articles from within the past year as well as from the past.
RECENT FINDINGS
Areas of recent interest include the evaluation of osteopontin and mesothelin as new tumor markers for mesothelioma. New phase III trials have been performed to evaluate the use of combined chemotherapy regimens.
SUMMARY
Malignant mesothelioma is a very difficult malignancy to treat. Patients with the disease usually have an occupational asbestos exposure, and in some, viral exposure with SV40. There have been many historical treatments including combinations of local control with surgery and radiation as well as attempts to prevent systemic failure with chemotherapy. Novel therapies including intrapleural chemotherapy, photodynamic therapy and hyperthermic perfusion have also been used with some success. Finally there are several attempts at immunomodulating and targeted treatments, which are in phase I/II trials.
Topics: Biomarkers, Tumor; Clinical Trials as Topic; Combined Modality Therapy; Diagnostic Imaging; Humans; Mesothelioma; Neoplasm Staging; Pleural Neoplasms; Prognosis
PubMed: 18520263
DOI: 10.1097/MCP.0b013e328302851d -
Respirology (Carlton, Vic.) Jun 2005Malignant mesothelioma is an insidious neoplasm arising from the mesothelial surfaces of the pleural and peritoneal cavities, the pericardium, or the tunica vaginalis. A... (Review)
Review
Malignant mesothelioma is an insidious neoplasm arising from the mesothelial surfaces of the pleural and peritoneal cavities, the pericardium, or the tunica vaginalis. A total of 80% of all cases are pleural in origin. The predominant cause of malignant mesothelioma is inhalational exposure to asbestos, although evidence is increasing to support the hypothesis that simian virus-40 virus plays a role in cocarcinogenesis. Immunohistochemical markers such as calretinin, WT-1, and cytokeratin 5/6 are becoming established diagnostic markers. Preliminary data suggests that a soluble form of mesothelin could serve as a serum marker for established and early cases of mesothelioma. Positron emission tomography with 18-fluorodeoxyglucose in conjunction with computed tomograhy scanning has improved preoperative imaging and staging. Prognostic factors have been identified and verified. Negative indicators include thrombocytosis, high leukocyte counts, poor performance status, and nonepithelial histology. For the first time, there is now evidence that some treatments are increasing the quality and quantity of life for patients with mesothelioma. Chemotherapy, with the new multi-targeted antifolate drug Pemetrexed, combined with cisplatin, has shown superior survival rates in a large phase III trial when compared to cisplatin alone. High-dose intensity-modulated radiotherapy when administered after extrapleural pneumonectomy has resulted in excellent local control. Multimodality treatment programs that combine surgical cytoreduction with novel forms of radiation therapy and more effective chemotherapy combinations may offer significant increases in survival for certain subgroups of mesothelioma patients. Innovative palliative approaches have proved successful in alleviation of the significant symptoms experienced by many mesothelioma patients. Experimental treatments such as immunotherapy and gene therapy present a window of hope for all mesothelioma patients, and in the future, may be combined with 'standard therapy' in multimodality protocols. Patients with adequate performance status should be enrolled into clinical trials where possible. Over the past decade, significant advances have been made on several fronts that have improved the ability to diagnose a stage, define prognosis, and treat malignant pleural mesothelioma.
Topics: Combined Modality Therapy; Global Health; Humans; Incidence; Mesothelioma; Pleural Neoplasms; Prognosis
PubMed: 15955137
DOI: 10.1111/j.1440-1843.2005.00714.x -
International Journal of Clinical... Feb 2012Malignant pleural mesothelioma (MPM) remains suffering poor prognosis in spite of recent diagnostic and therapeutic progress. Although there is currently no established... (Review)
Review
Malignant pleural mesothelioma (MPM) remains suffering poor prognosis in spite of recent diagnostic and therapeutic progress. Although there is currently no established evidence, early diagnosis and early intervention may play a key role to improve prognosis of MPM, similarly to other malignancies. As pleural effusion is usually the first clinical sign of MPM, pleural effusion cytology is often the first diagnostic examination to be carried out. Since the sensitivity of pleural effusion cytology is approximately 60%, however, false-negative diagnosis is given to almost half of true MPM patients at this clinical step. One practical way to reduce the number of misdiagnosed MPM is to encourage performing thoracoscopic pleural biopsy unless definitive diagnosis other than MPM is established. There still remain a considerable number of patients with radiological/thoracoscopic T0 MPM who are misdiagnosed with nonspecific pleuritis after a complete investigation including thoracoscopic biopsies. Such patients will turn out to be malignant during follow-up period, although they have the best opportunity for long-term survival if only early therapeutic intervention is given. Currently, we are performing diagnostic total parietal pleurectomy in highly selected patients, who are characterized with strong clinical suspicion, positive pleural effusion cytology but uncertain pathological diagnosis, excellent cardiopulmonary reserve, and with written informed consent for highly invasive diagnostic surgery for pathologically unproven disease.
Topics: Early Detection of Cancer; Humans; Mesothelioma; Neoplasm Staging; Pleura; Pleural Effusion, Malignant; Pleural Neoplasms; Prognosis
PubMed: 22237726
DOI: 10.1007/s10147-011-0368-2 -
Kyobu Geka. the Japanese Journal of... Feb 2007We report a 58-year-old male with localized pleural adenocarcinoma, the origin of which was not identified. The disk-shaped pleural tumor was 8 x 6 x 2 cm in size and...
We report a 58-year-old male with localized pleural adenocarcinoma, the origin of which was not identified. The disk-shaped pleural tumor was 8 x 6 x 2 cm in size and involved the left upper chest wall including the ribs. A fine needle biopsy showed adenocarcinoma, but whole body survey revealed no neoplasm other than the chest wall tumor. The left chest wall resection was followed by the left pleuropneumonectomy, because a few disseminations were identified in the visceral pleura. Pathological examinations showed no primary tumor in the lung. Immunohistochemical examinations suggested that micro-adenocarcinoma originating the subpleural lung invaded chest wall. It may be possibly a subtype of pseudomesotheliomatous adenocarcinoma. The patient has no recurrent tumor 1 year after the operation.
Topics: Adenocarcinoma; Diagnosis, Differential; Humans; Male; Mesothelioma; Middle Aged; Neoplasm Invasiveness; Neoplasm Staging; Pleural Neoplasms; Thoracic Surgical Procedures
PubMed: 17305076
DOI: No ID Found -
Seminars in Ultrasound, CT, and MR Dec 2017Malignant pleural mesothelioma is the most common primary neoplasm of the pleura. Imaging evaluation is essential in diagnosis, staging, and assessment of treatment...
Malignant pleural mesothelioma is the most common primary neoplasm of the pleura. Imaging evaluation is essential in diagnosis, staging, and assessment of treatment response in malignant pleural mesothelioma. Computed tomography is the most commonly used modality for tumor staging. Assessment of tumor extension and lymph node involvement is essential in imaging evaluation as locally advanced tumors are amenable to resection. Knowledge of the full imaging spectrum of this rare disease, differential diagnosis, staging classification, and the current guidelines for diagnostic evaluation and follow-up are essential in accurate interpretation to optimize patient management.
Topics: Diagnosis, Differential; Diagnostic Imaging; Follow-Up Studies; Humans; Lung Neoplasms; Mesothelioma; Mesothelioma, Malignant; Neoplasm Staging; Pleural Neoplasms; Risk Factors
PubMed: 29179896
DOI: 10.1053/j.sult.2017.07.006 -
Japanese Journal of Radiology Jan 2024Pleural mesothelioma (PM) is an aggressive disease that has a strong causal relationship with asbestos exposure and represents a major challenge from both a diagnostic... (Review)
Review
Pleural mesothelioma (PM) is an aggressive disease that has a strong causal relationship with asbestos exposure and represents a major challenge from both a diagnostic and therapeutic viewpoint. Despite recent improvements in patient care, PM typically carries a poor outcome, especially in advanced stages. Therefore, a timely and effective diagnosis taking advantage of currently available imaging techniques is essential to perform an accurate staging and dictate the most appropriate treatment strategy. Our aim is to provide a brief, but exhaustive and up-to-date overview of the role of multimodal medical imaging in the management of PM.
Topics: Humans; Neoplasm Staging; Mesothelioma; Pleural Neoplasms; Risk Factors; Multimodal Imaging
PubMed: 37676382
DOI: 10.1007/s11604-023-01480-5 -
International Journal of Molecular... Mar 2021Malignant pleural mesothelioma (MPM) is a fatal tumor lacking effective therapies. The characterization of overexpressed genes could constitute a strategy for...
Malignant pleural mesothelioma (MPM) is a fatal tumor lacking effective therapies. The characterization of overexpressed genes could constitute a strategy for identifying drivers of tumor progression as targets for novel therapies. Thus, we performed an integrated gene-expression analysis on RNAseq data of 85 MPM patients from TCGA dataset and reference samples from the GEO. The gene list was further refined by using published studies, a functional enrichment analysis, and the correlation between expression and patients' overall survival. Three molecular signatures defined by 15 genes were detected. Seven genes were involved in cell adhesion and extracellular matrix organization, with the others in control of the mitotic cell division or apoptosis inhibition. Using Western blot analyses, we found that ADAMTS1, PODXL, CIT, KIF23, MAD2L1, TNNT1, and TRAF2 were overexpressed in a limited number of cell lines. On the other hand, interestingly, CTHRC1, E-selectin, SPARC, UHRF1, PRSS23, BAG2, and MDK were abundantly expressed in over 50% of the six MPM cell lines analyzed. Thus, these proteins are candidates as drivers for sustaining the tumorigenic process. More studies with small-molecule inhibitors or silencing RNAs are fully justified and need to be undertaken to better evaluate the cancer-driving role of the targets herewith identified.
Topics: Female; Gene Expression Regulation, Neoplastic; Humans; Male; Mesothelioma, Malignant; Neoplasm Proteins; Pleural Neoplasms
PubMed: 33800494
DOI: 10.3390/ijms22052738