scholarly journals Cytomegalovirus infection in malignant pleural mesothelioma

PLoS ONE ◽  
2021 ◽  
Vol 16 (8) ◽  
pp. e0254136
Author(s):  
DeVon Hunter-Schlichting ◽  
Karl T. Kelsey ◽  
Ryan Demmer ◽  
Manish Patel ◽  
Raphael Bueno ◽  
...  
Keyword(s):  
Malignant Pleural Mesothelioma ◽  
Hcmv Infection ◽  
Case Series ◽  
Pleural Mesothelioma ◽  
Full Spectrum ◽  
Hcmv Disease ◽  
Current Infection ◽  
High Level ◽  
Tumor Types ◽  
Pleural Tissue

Human cytomegalovirus (HCMV) is a highly prevalent herpes virus which persists as a latent infection and has been detected in several different tumor types. HCMV disease is rare but may occur in high-risk settings, often manifesting as a pulmonary infection. To date HCMV has not been investigated in malignant pleural mesothelioma (MPM). In a consecutive case series of 144 MPM patients we evaluated two biomarkers of HCMV: IgG serostatus (defined as positive and negative) and DNAemia (>100 copies/mL of cell free HCMV DNA in serum). Approximately half of the MPM patient population was HCMV IgG seropositive (51%). HCMV DNAemia was highly prevalent (79%) in MPM and independent of IgG serostatus. DNAemia levels consistent with high level current infection (>1000 copies/mL serum) were present in 41% of patients. Neither IgG serostatus nor DNAemia were associated with patient survival. In tissues, we observed that HCMV DNA was present in 48% of tumors (n = 40) and only 29% of normal pleural tissue obtained from individuals without malignancy (n = 21). Our results suggest nearly half of MPM patients have a high level current HCMV infection at the time of treatment and that pleural tissue may be a reservoir for latent HCMV infection. These findings warrant further investigation to determine the full spectrum of pulmonary infections in MPM patients, and whether treatment for high level current HCMV infection may improve patient outcomes.

scholarly journals A review of malignant pleural mesothelioma in a large North East UK pleural centre

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Declan C. Murphy ◽  
Alexander Mount ◽  
Fiona Starkie ◽  
Leah Taylor ◽  
Avinash Aujayeb
Keyword(s):  
Malignant Pleural Mesothelioma ◽  
Survival Rates ◽  
Case Series ◽  
Pleural Mesothelioma ◽  
Retrospective Case ◽  
Pleural Thickening ◽  
North East ◽  
Total Cohort ◽  
Anti Cancer ◽  
One Year

AbstractObjectivesThe National Mesothelioma Audit 2020 showed Northumbria to have low rates of histopathological confirmation, treatment and one-year survival rates for malignant pleural mesothelioma (MPM). We hypothesized that an internal analysis over a 10-year period provides valuable insights into presentation, diagnosis, treatment and outcomes.MethodsA single-centre retrospective case series of all confirmed MPM patients between 1 January 2009 and 31 December 2019 was performed. Demographics, clinical, radiological and histopathological characteristics and outcomes were collected. Statistical analysis was performed using SPSS V26.0.ResultsA total of 247 patients had MPM. About 86% were male, mean age 75.7 years. Dyspnoea (77.4%) and chest pain (38.5%) were commonest symptoms. 64.9 and 71.4% had pleural thickening and effusion, respectively. About 86.8% had at least one attempt to obtain a tissue biopsy, but histopathological confirmation in only 108 (43.7%). About 66.3% with PS 0 and 1 (62.7% of total cohort) had at least one anti-cancer therapy. Death within 12 months was associated with disease progression within 6 months (p≤0.001). Chemotherapy (p≤0.001) and epithelioid histological subtype (p=0.01) were protective.ConclusionsThis study confirms known epidemiology of MPM, demonstrates variability in practices and highlights how some NMA recommendations are not met. This provides the incentive for a regional mesothelioma multi-disciplinary meeting.

On the diagnosis of malignant pleural mesothelioma: A necropsy-based study of 171 cases (1997–2016)

2018 ◽  
Vol 105 (4) ◽  
pp. 304-311 ◽  
Author(s):  
Pietro Gino Barbieri ◽  
Dario Mirabelli ◽  
Corrado Magnani ◽  
Alessandro Brollo
Keyword(s):  
Malignant Pleural Mesothelioma ◽  
Case Series ◽  
Pleural Mesothelioma ◽  
Cytologic Examination ◽  
Pleural Plaques ◽  
Radiologic Imaging ◽  
High Positive Predictive Value ◽  
Low Sensitivity ◽  
Clinical Records ◽  
Shipyard Workers

Background:Malignant pleural mesothelioma (MPM) diagnosis is known to be difficult. We report on the diagnostic elements available in life in an MPM necropsy case series and describe the frequency of non-neoplastic asbestos-related diseases as biological exposure indices.Methods:We reviewed pathologic and clinical records of an unselected series of autopsies (1977–2016) in patients with MPM employed in the Monfalcone shipyards or living with shipyard workers. We assessed the consistency with autopsy results of diagnoses based on, respectively, radiologic, cytologic, and histologic findings, with and without immunophenotyping.Results:Data on 171 cases were available: for 169, autopsy confirmed the MPM diagnosis. In life, 119 cases had histologic confirmation of diagnosis, whereas 7 were negative; all cases without immunophenotypization were autoptic MPMs. Cytology alone had been positive in 18 autoptic MPM cases, negative in 14. Radiologic imaging alone had been positive in another 16, negative in 11. In the 2 cases not confirmed at autopsy, MPM had been suspected by chest computed tomography only. Bilateral pleural plaques were found in 144 and histologic evidence of asbestosis in 62 cases.Conclusions:Autopsies confirmed 169/171 cases, including cases that would not be considered as certain based on diagnosis in life. Radiologic imaging, cytologic examination of pleural effusions, or both combined had low sensitivity but high positive predictive value: when they are positive, proceeding to thoracoscopy should be justified. MPM has been correctly diagnosed even without immunohistochemistry. The prevalence of pleural plaques and asbestosis was high due to severity of asbestos exposures in these cases.

scholarly journals miR-182 facilitates invasion and EMT by targeting Numb in Malignant Pleural Mesothelioma

2020 ◽  
Author(s):  
Yanmeng Kang ◽  
Degan Lu ◽  
Lingxia Meng ◽  
Ruiping Ma ◽  
Chuanjun Huang ◽  
...  
Keyword(s):  
Malignant Pleural Mesothelioma ◽  
Luciferase Reporter ◽  
Pleural Mesothelioma ◽  
Reporter Plasmid ◽  
Luciferase Reporter Plasmid ◽  
Aggressive Tumor ◽  
High Level ◽  
The Impact ◽  
Test Correlation

Abstract Background Malignant Pleural Mesothelioma (MPM) is a highly aggressive tumor which need effective therapeutic methods to improve the prognosis. We carried out this study to explore the role of miR-182 in MPM development, its correlation with Numb expression and EMT. Methods First, we investigated the level of miR-182 and Numb-mRNA by qRT-PCR. Furthermore, we introduced the putative miR-182 binding site into a luciferase reporter plasmid to illustrate the impact of miR-182 on Numb. Then, we down-regulated the expression of miR-182 with/without Numb knocked down in NCI-H2452 cells to investigated their effect. Data were presented as mean ± SD of three independent experiments. Student’s test, correlation analysis and analysis of variance (ANOVA) were used. Results Our results revealed that miR-182 has a high level of expression in MPM, it has a negative correlation with Numb and targeted Numb in MPM cells. miR-182 facilitated the invasion of MPM cells while down-regulation of miR-182 restrained the progression of EMT and made MPM cells more susceptible to pemetrexed. Conclusions miR-182 and Numb can serve as potential therapeutic targets for MPM.

scholarly journals Serum levels of the chemokine CCL2 are elevated in malignant pleural mesothelioma patients

2019 ◽  
Author(s):  
Takumi Kishimoto ◽  
Nobukazu Fujimoto ◽  
Takeshi Ebara ◽  
Toyonori Omori ◽  
Tetsuya Oguri ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Malignant Pleural Mesothelioma ◽  
Tissue Damage ◽  
Serum Levels ◽  
Pleural Mesothelioma ◽  
Asbestos Fibers ◽  
Chemokine Ligand ◽  
History Of ◽  
Tumor Types ◽  
Study Participants

Abstract Background: Malignant pleural mesothelioma (MPM) is a debilitating disease of the pleural cavity. It is primarily associated with previous inhalation of asbestos fibers. These fibers initiate an oxidant coupled inflammatory response. Repeated exposure to asbestos fibers results in a prolonged inflammatory response and cycles of tissue damage and repair. The inflammation-associated cycles of tissue damage and repair are intimately involved in the development of asbestos-associated cancers. Macrophages are a key component of asbestos-associated inflammation and play essential roles in the etiology of a variety of cancers. Macrophages are also a source of C-C motif chemokine ligand 2 (CCL2), and a variety of tumor-types express CCL2. High levels of CCL2 are present in the pleural effusions of mesothelioma patients, however, CCL2 has not been examined in the serum of mesothelioma patients. Methods: The present study was carried out with 50 MPM patients and 356 subjects who were possibly exposed to asbestos but did not have disease symptoms and 41 healthy volunteers without a history of exposure to asbestos. The levels of CCL2 in the serum of the study participants was determined using ELISA. Results: Levels of CCL2 were significantly elevated in the serum of patients with advanced MPM patients. Conclusions: Our findings are consistent with the premise that the CCL2/CCR2 axis and myeloid-derived cells play an important role in MPM and disease progression. Therapies are being developed that target CCL2/CCR2 and tumor resident myeloid cells, and clinical trials are being pursued that use these therapies as part of the treatment regimen. The results of trials with patients with a similar serum CCL2 pattern as MPM patients will have important implications for the treatment of MPM.

Treatment outcomes in malignant pleural mesothelioma: A single center experience of systemic therapies and biomarkers.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e20070-e20070
Author(s):  
Adithya Balasubramanian ◽  
Adrian Pick ◽  
Beena Kumar ◽  
Zdenka Prodanovic ◽  
Prashant Joshi ◽  
...  
Keyword(s):  
Malignant Pleural Mesothelioma ◽  
Survival Data ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Asbestos Exposure ◽  
Case Series ◽  
Stage Iv ◽  
Pleural Mesothelioma ◽  
Retrospective Audit

e20070 Background: Malignant Pleural Mesothelioma (MPM) is a rare but fatal disease related to asbestos exposure, with historic survival in the order of 9 to 17 months. Chemotherapy is associated with only a modest benefit. The advent of immunotherapy has heralded significantly improved outcomes using checkpoint inhibitors in an as yet ill-defined cohort. We aim to identify predictive and prognostic biomarkers in a series of patients (pts) with MPM and describe survival data. Methods: A retrospective audit was undertaken of pts with MPM diagnosed between 2013 and 2017 at a single tertiary centre in Melbourne, Australia (Monash Health). Data relating to patient outcomes and clinicopathological features were obtained through medical reports. Further immunostains are being performed on archived tissue for PDL-1 status. Results: 65 pts were identified, of whom 52 (80.0%) were male. Median age was 73 years (range 44-90). 52 pts were noted to be ECOG 0-1. 42 pts (64.6%) were noted to have suspected asbestos exposure. Epithelioid MPM was the most common subtype, noted in 41 pts (63.1%) (table 1). 8 pts (12.3%) presented with stage IV disease. 16 pts (24.6%) received checkpoint inhibitor therapy, with 10 (63 %) in the second/third line setting. Median overall survival (OS) was 19.8 months (95% CI 13.3-26.3) in the whole cohort.Patient characteristics associated with poor OS were: presence of weight loss (P = 0.001), chest pain (p = 0.08) and ECOG 2 (p = 0.04). Pts with sarcomatoid histology who received immune checkpoint inhibitors in any line of treatment had significantly prolonged OS compared to other histologies. 3-year survival was 80% in this group while median OS was not reached (p = 0.04). This difference was not seen with other histologies. Conclusions: The evolving landscape of treatment in MPM appears to show promise in improving OS. In this unselected case series, our data is consistent with historic controls in terms of survival and prognostic factors. The finding of significantly improved survival with immune checkpoint inhibitors in the sarcomatoid histology is exciting and warrants further exploration. Further data on PDL1 status will be presented.

scholarly journals Diagnostic Challenges in Epithelioid Pleural Mesothelioma: Case Series with Support from Electron Microscopy

Diagnostics ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 841
Author(s):  
Francesco Fortarezza ◽  
Mila Della Barbera ◽  
Federica Pezzuto ◽  
Francesca Lunardi ◽  
Eleonora Faccioli ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Malignant Pleural Mesothelioma ◽  
Rare Variants ◽  
Case Series ◽  
Morphological Characteristics ◽  
Pleural Mesothelioma ◽  
Ultrastructural Examination ◽  
Specific Diagnosis ◽  
Final Interpretation ◽  
Definition Of

The histological diagnosis of pleural epithelioid mesothelioma can be difficult in the case of rare variants or in the definition of neoplasm origin in patients with previous or concomitant tumours. Currently, several immunohistochemical reactions are available in the surgical pathologist’s armamentarium that allow us to obtain a more sensitive and specific diagnosis of malignant pleural mesothelioma. However, in some cases, the final interpretation remains inconclusive. Historically, ultrastructural examination has represented a useful tool for the definition of the mesothelial nature of neoplastic cells due to their peculiar morphological characteristics. The recent international guidelines for pathological diagnosis of pleural mesothelioma suggest the use of electron microscopy when the immunohistochemical reactions are equivocal or when further support of a diagnosis of mesothelioma is needed. This paper presents three cases of pleural epithelioid mesothelioma whose diagnoses were finally supported by ultrastructural examination.

scholarly journals A Trimodality, Four-Step Treatment including Chemotherapy, Pleurectomy/Decortication and Radiotherapy in Early-Stage Malignant Pleural Mesothelioma: A Single-Institution Retrospective Case Series Study

Cancers ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 142
Author(s):  
Giovanni Vicidomini ◽  
Carminia Maria Della Corte ◽  
Antonio Noro ◽  
Raimondo Di Liello ◽  
Salvatore Cappabianca ◽  
...  
Keyword(s):  
Malignant Pleural Mesothelioma ◽  
Early Stage ◽  
Objective Response ◽  
Case Series ◽  
Cardiac Massage ◽  
Pleural Mesothelioma ◽  
Retrospective Case ◽  
Intraoperative Complication ◽  
Retrospective Case Series ◽  
Case Series Study

Background: Multimodality treatment is considered the best treatment strategy for malignant pleural mesothelioma (MPM). However, the ideal combination of them is still a matter of controversy. Here, we report a case series of MPM treated with a trimodality approach: induction chemotherapy (CT), pleurectomy/decortication (P/D), postoperative radiotherapy (RT) and post-operative CT. Methods: A retrospective case series of 17 MPM patients treated between 2013 and 2020 is presented. Patients had epithelial or mixed MPM diagnosed by video-assisted thoracoscopy and pathologic IMIG stage I or II disease. Treatment details and radiological data were collected. Induction therapy consisted of combination of cisplatin and pemetrexed, every 21 days for two cycles. P/D was performed 4–6 weeks after induction CT, post-operative RT 3–6 weeks after surgery, while post-operative CT was given 4–6 weeks after RT, with the same schedule of induction. Results: All patients showed objective response or stability of disease at the restaging following induction CT and underwent surgery by posterolateral thoracotomy. There were two cases of cardiac arrest as major intraoperative complication, both resolved by manual cardiac massage. Minor complications included one hemidiaphragm elevation, 1 anemia requiring blood transfusion, one wound infection, and two persistent air leaks. Median overall survival was 32.1 months, median progression free survival was 23.7 months. Conclusions: These results suggest the feasibility of these trimodality treatment scheme for early stage MPM patients. Larger series and long-term prospective studies are needed to confirm the validity of this strategy.

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