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Fulltext Differential p16/INK4A cyclin-dependent kinase inhibitor expression correlates with chemotherapy efficacy in a cohort of 88 malignant pleural mesothelioma patients

Jennings CJ, Murer B, O'Grady A, Hearn LM, Harvey BJ, Kay EW, et al.

Br. J. Cancer, 2015 Jun 30;113(1):69-75.
PMID: 26057448 DOI: 10.1038/bjc.2015.187

Malignant pleural mesothelioma (MPM) is a rare and essentially incurable malignancy most often linked with occupational exposure to asbestos fibres. In common with other malignancies, the development and progression of MPM is associated with extensive dysregulation of cell cycle checkpoint proteins that modulate cell proliferation, apoptosis, DNA repair and senescence.

Matched MeSH terms: Mesothelioma/drug therapy*; Mesothelioma/metabolism; Mesothelioma/pathology
Fulltext MRI appearances of peritoneal mesothelioma--a case report

Hashim S, Abdullah BJJ, Jayaram G

Med J Malaysia, 1999 Sep;54(3):358-60.
PMID: 11045063

A rare case of diffuse malignant peritoneal mesothelioma in a 71 year-old Malay man with no previous history of asbestos or radiation exposure is described. The clinical manifestation was a large abdominal mass. At laparotomy he was found to be in the advanced stage of the disease. The tumour was not resectable and patient was sent home. He gradually deteriorated and died three months after diagnosis was made. The magnetic resonance imaging (MRI) features of peritoneal mesothelioma which has not been previously reported are described.

Matched MeSH terms: Mesothelioma/diagnosis*
Fulltext Gender-Specific Molecular and Clinical Features Underlie Malignant Pleural Mesothelioma

De Rienzo A, Archer MA, Yeap BY, Dao N, Sciaranghella D, Sideris AC, et al.

Cancer Res, 2016 Jan 15;76(2):319-28.
PMID: 26554828 DOI: 10.1158/0008-5472.CAN-15-0751

Malignant pleural mesothelioma (MPM) is an aggressive cancer that occurs more frequently in men, but is associated with longer survival in women. Insight into the survival advantage of female patients may advance the molecular understanding of MPM and identify therapeutic interventions that will improve the prognosis for all MPM patients. In this study, we performed whole-genome sequencing of tumor specimens from 10 MPM patients and matched control samples to identify potential driver mutations underlying MPM. We identified molecular differences associated with gender and histology. Specifically, single-nucleotide variants of BAP1 were observed in 21% of cases, with lower mutation rates observed in sarcomatoid MPM (P < 0.001). Chromosome 22q loss was more frequently associated with the epithelioid than that nonepitheliod histology (P = 0.037), whereas CDKN2A deletions occurred more frequently in nonepithelioid subtypes among men (P = 0.021) and were correlated with shorter overall survival for the entire cohort (P = 0.002) and for men (P = 0.012). Furthermore, women were more likely to harbor TP53 mutations (P = 0.004). Novel mutations were found in genes associated with the integrin-linked kinase pathway, including MYH9 and RHOA. Moreover, expression levels of BAP1, MYH9, and RHOA were significantly higher in nonepithelioid tumors, and were associated with significant reduction in survival of the entire cohort and across gender subgroups. Collectively, our findings indicate that diverse mechanisms highly related to gender and histology appear to drive MPM.

Matched MeSH terms: Mesothelioma/genetics*; Mesothelioma/pathology
Fulltext Global economic burden of asbestos related diseases in comparison with the costs of production and consumption

Syed Mohamed Aljunid, Ahmad Munir Qureshi, David B

Malaysian Journal of Public Health Medicine, 2017;17(1):111-125.

Occupational cancers, including mesothelioma and lung cancer are linked to the use of asbestos. Annually, at least 100,000 global deaths are attributed to asbestos exposure putting a heavy burden on national budgets. Expenses incurred on treatment of asbestos related diseases (ARDs) reduce households and national resource savings, while ARDs culminate in terminal burdens. The objective of this study is to measure the economic burden of ARDs and to assess the economic impact of asbestos consumption. The health and economic burden of asbestos was estimated in macro-global consumption-production model using production function frontier-based and generalized least squared approach for asbestos products and cost tabulation. Production, in metric tons (Mt) was adopted as a dependent variable among explanatory variables, including consumption. Information on treatment cost of asbestos related diseases (mesothelioma, asbestosis and lung cancer) was obtained from costing information and published literatures. Annual total economic burden of asbestos is at USD 11.92 billion. Out of this cost, USD 4.34 billion per annum is the economic burden of managing three common ARDs. The cost of compensation for patients suffering ARDs is USD 4.28 billion. From the remaining USD 3.3 billion, USD 2.93 billion is the value of asbestos consumed in 2003 and USD372.15 million is the loss of earning due to hospital visits and admissions. For every USD 1 spent on consumption of asbestos, global economy has to absorb almost USD 4 due to health consequences of ARDs. Banning of asbestos production and usage in production of goods has far-reaching impacts on household welfare, health and economic development. The insights revealed are expected to inform decision makers the need to ban all forms of asbestos, especially in developing countries where usage is increasing.

Matched MeSH terms: Mesothelioma
Fulltext Frequency of Germline Mutations in Cancer Susceptibility Genes in Malignant Mesothelioma

Panou V, Gadiraju M, Wolin A, Weipert CM, Skarda E, Husain AN, et al.

J Clin Oncol, 2018 Oct 01;36(28):2863-2871.
PMID: 30113886 DOI: 10.1200/JCO.2018.78.5204

PURPOSE: The aim of the current study was to determine the prevalence and clinical predictors of germline cancer susceptibility mutations in patients with malignant mesothelioma (MM).
METHODS: We performed targeted capture and next-generation sequencing of 85 cancer susceptibility genes on germline DNA from 198 patients with pleural, peritoneal, and tunica vaginalis MM.
RESULTS: Twenty-four germline mutations were identified in 13 genes in 23 (12%) of 198 patients. BAP1 mutations were the most common (n = 6; 25%). The remaining were in genes involved in DNA damage sensing and repair (n = 14), oxygen sensing (n = 2), endosome trafficking (n = 1), and cell growth (n = 1). Pleural site (odds ratio [OR], 0.23; 95% CI, 0.10 to 0.58; P < .01), asbestos exposure (OR, 0.28; 95% CI, 0.11 to 0.72; P < .01), and older age (OR, 0.95; 95% CI, 0.92 to 0.99; P = .01) were associated with decreased odds of carrying a germline mutation, whereas having a second cancer diagnosis (OR, 3.33; 95% CI, 1.22 to 9.07; P = .02) significantly increased the odds. The odds of carrying a mutation in BAP1 (OR, 1,658; 95% CI, 199 to 76,224; P < .001), BRCA2 (OR, 5; 95% CI, 1.0 to 14.7; P = .03), CDKN2A (OR, 53; 95% CI, 6 to 249; P < .001), TMEM127 (OR, 88; 95% CI, 1.7 to 1,105; P = .01), VHL (OR, 51; 95% CI, 1.1 to 453; P = .02), and WT1 (OR, 20; 95% CI, 0.5 to 135; P = .049) were significantly higher in MM cases than in a noncancer control population. Tumor sequencing identified mutations in a homologous recombination pathway gene in 52% (n = 29 of 54).
CONCLUSION: A significant proportion of patients with MM carry germline mutations in cancer susceptibility genes, especially those with peritoneal MM, minimal asbestos exposure, young age, and a second cancer diagnosis. These data support clinical germline genetic testing for patients with MM and provide a rationale for additional investigation of the homologous recombination pathway in MM.

Matched MeSH terms: Mesothelioma/genetics*
Fulltext Protocol of the Australasian Malignant Pleural Effusion-2 (AMPLE-2) trial: a multicentre randomised study of aggressive versus symptom-guided drainage via indwelling pleural catheters

Azzopardi M, Thomas R, Muruganandan S, Lam DC, Garske LA, Kwan BC, et al.

BMJ Open, 2016 07 05;6(7):e011480.
PMID: 27381209 DOI: 10.1136/bmjopen-2016-011480

INTRODUCTION: Malignant pleural effusions (MPEs) can complicate most cancers, causing dyspnoea and impairing quality of life (QoL). Indwelling pleural catheters (IPCs) are a novel management approach allowing ambulatory fluid drainage and are increasingly used as an alternative to pleurodesis. IPC drainage approaches vary greatly between centres. Some advocate aggressive (usually daily) removal of fluid to provide best symptom control and chance of spontaneous pleurodesis. Daily drainages however demand considerably more resources and may increase risks of complications. Others believe that MPE care is palliative and drainage should be performed only when patients become symptomatic (often weekly to monthly). Identifying the best drainage approach will optimise patient care and healthcare resource utilisation.
METHODS AND ANALYSIS: A multicentre, open-label randomised trial. Patients with MPE will be randomised 1:1 to daily or symptom-guided drainage regimes after IPC insertion. Patient allocation to groups will be stratified for the cancer type (mesothelioma vs others), performance status (Eastern Cooperative Oncology Group status 0-1 vs ≥2), presence of trapped lung (vs not) and prior pleurodesis (vs not). The primary outcome is the mean daily dyspnoea score, measured by a 100 mm visual analogue scale (VAS) over the first 60 days. Secondary outcomes include benefits on physical activity levels, rate of spontaneous pleurodesis, complications, hospital admission days, healthcare costs and QoL measures. Enrolment of 86 participants will detect a mean difference of VAS score of 14 mm between the treatment arms (5% significance, 90% power) assuming a common between-group SD of 18.9 mm and a 10% lost to follow-up rate.
ETHICS AND DISSEMINATION: The Sir Charles Gairdner Group Human Research Ethics Committee has approved the study (number 2015-043). Results will be published in peer-reviewed journals and presented at scientific meetings.
TRIAL REGISTRATION NUMBER: ACTRN12615000963527; Pre-results.

Matched MeSH terms: Mesothelioma/epidemiology; Mesothelioma/prevention & control*
Well-differentiated Papillary Mesothelioma of the Tunica Vaginalis

Tan WK, Tan MY, Tan HM, Pathmanathan R, Tan WP

Urology, 2016 Apr;90:e7-8.
PMID: 26773348 DOI: 10.1016/j.urology.2015.12.046

A 39-year-old man presented with painless scrotal swelling for 2 months. He denied any asbestos exposure but worked with wall and ceiling plaster. Physical exam revealed a large right scrotum which transilluminated. Scrotal ultrasonography revealed a large right hydrocele and a polypoidal mass along the anterior wall of the scrotum. Magnetic resonance imaging of the abdomen and computed tomography of the chest showed no metastases. He underwent a right inguinal scrotal exploration and wide excision of tunica vaginalis and a partial epididymectomy. Pathology revealed well-differentiated papillary mesothelioma of the tunica vaginalis. The patient had an uneventful recovery.

Matched MeSH terms: Mesothelioma
Tamoxifen Suppresses the Growth of Malignant Pleural Mesothelioma Cells

Jennings CJ, Zainal N, Dahlan IM, Kay EW, Harvey BJ, Thomas W

Anticancer Res, 2016 11;36(11):5905-5913.
PMID: 27793915

Malignant pleural mesothelioma (MPM) is a rare but highly aggressive malignancy most often associated with exposure to asbestos. Recent evidence points to oestrogen receptor (ER)-β having a tumour-suppressor role in MPM progression, and this raises the question of whether selective modulators of ERs could play a role in augmenting MPM therapy.

Matched MeSH terms: Mesothelioma/pathology*