Malignant pleural mesothelioma: an update on investigation, diagnosis and treatment

Malignant pleural mesothelioma is an aggressive malignancy of the pleural surface, predominantly caused by prior asbestos exposure. There is a global epidemic of malignant pleural mesothelioma underway, and incidence rates are predicted to peak in the next few years.

This article summarises the epidemiology and pathogenesis of malignant pleural mesothelioma, before describing some key factors in the patient experience and outlining common symptoms. Diagnostic approaches are reviewed, including imaging techniques and the role of various biomarkers. Treatment options are summarised, including the importance of palliative care and methods of controlling pleural effusions. The evidence for chemotherapy, radiotherapy and surgery is reviewed, both in the palliative setting and in the context of trimodality treatment. An algorithm for managing malignant pleural effusion in malignant pleural mesothelioma patients is presented. Finally new treatment developments and novel therapeutic approaches are summarised.

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Source: Malignant pleural mesothelioma: an update on investigation, diagnosis and treatment


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Primary pericardial mesothelioma and asbestos exposure: a rare fatal disease

A 73-year-old woman without a history of cardiovascular disease was admitted to the hospital with progressive dyspnoea on exertion during the past several weeks, bilateral lower extremity oedema, orthopnoea and paroxistic nocturnal dyspnoea. She lived a few metres away from a badly preserved building containing asbestos for 50 years. Estimated jugular venous pressure was 6+5 cm H2O, a pericardial friction rub was heard, bilateral basal lung crackles were present and symmetrical below-knee pitting oedema was seen. Probrain natriuretic peptide was 2304?pg/mL, and chest radiograph showed a globular cardiac silhouette and blunting of the costophrenic angles due to a small transudative pleural effusion containing benign mesothelial cells on cytological analysis. Transthoracic echocardiogram showed a large pericardial effusion with diastolic collapse of the right ventricle and a hypotransparent mass (4×1.6?cm) attached to the visceral pericardium in the right apex (video 1). Therapeutic pericardiocentesis was performed and cytological analysis of pericardial fluid demonstrated malignant cells of inconclusive origin. CT scan of the chest, abdomen and pelvis, mammography and upper and lower gastrointestinal endoscopies showed no evidence of extracardiac disease. A primary cardiac tumour was assumed and positron emission tomography-CT was done, as a part of the staging workup, demonstrating isolated hyperfixation in the apex and right atrium.

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Source: Primary pericardial mesothelioma and asbestos exposure: a rare fatal disease


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Midkine is a potential novel marker for malignant mesothelioma with different prognostic and diagnostic values from mesothelin

Background  We evaluated possible diagnostic and prognostic values of serum midkine in malignant pleural mesothelioma in comparison with those of serum mesothelin, a well-established diagnostic biomarker.

Methods  Serum mesothelin and midkine levels were determined with an enzyme-linked immunosorbent assay. We examined specimens from 95 Turkish cases with malignant pleural mesothelioma, 56 metastatic cancers to pleura, 27 other types of benign pleural diseases and 20 benign asbestos pleurisy….

Conclusions  Serum mesothelin showed moderate sensitivity and high specificity to differentiate malignant pleural mesothelioma from metastatic malignancy to pleura and from benign pleural diseases. In contrast, midkine was a useful marker for predicting prognosis of mesothelioma patients.

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Source: Midkine is a potential novel marker for malignant mesothelioma with different prognostic and diagnostic values from mesothelin


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Asbestos expert warns ageing population will drive surge in mesothelioma deaths

AN ASBESTOS expert has warned that the number of men dying from a lethal lung disease caused by exposure to the mineral is likely to triple over the next 30 years.

Robin Howie said official predictions had “vastly underestimated” the death toll from mesothelioma, an incurable cancer, because they fail to take account of future improvements in life expectancy.

Mr Howie, an Edinburgh-based occupational hygienist who advises on health and safety, said that the expected surge in people living into the 80s and older meant that increasing numbers of men would survive long enough to develop mesothelioma, whereas past generations tended to die earlier from other illnesses. The condition takes 42 years on average to develop after initial exposure.

Source: Asbestos expert warns ageing population will drive surge in mesothelioma deaths


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Pleural malignant mesothelioma in dental laboratory technicians: A case series

Asbestos was used in dentistry as a binder in periodontal dressings and as lining material for casting rings and crucible. However, until now, only one case of malignant mesothelioma with occupational exposure to asbestos in dental practice has been reported. We present 4 pleural mesotheliomas out of 5344 cases identified in Lombardy, Italy, in 2000-2014. Three men had been working as dental laboratory technicians, with asbestos exposure for 10, 34, and 4 years, and one woman had been helping her husband for 30 years in manufacturing dental prostheses. The men described the use of asbestos as a lining material for casting rings, while the woman was not able to confirm this use. We confirm the association of malignant mesothelioma with dental technician work. Dental technicians suffering from mesothelioma should be questioned about past occupational asbestos exposure.

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Source: Pleural malignant mesothelioma in dental laboratory technicians: A case series


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Asbestos Deaths Remain A Public Health Problem

People are still dying of cancer linked to asbestos, the U.S. Centers for Disease Control says, despite decades of regulations meant to limit dangerous exposure.

Starting in 1971, the Occupational Safety and Health Administration has regulated how much asbestos workers can be exposed to, because it contains tiny fibers that can cause lung disease or cancer if they are swallowed or inhaled.

The Environmental Protection Agency regulates asbestos too, setting requirements for inspecting, demolishing and renovating buildings that contain materials made with asbestos, like insulation, vinyl tiles, roofing, shingles and paint.

But, a recent CDC analysis found that thousands of people are still dying each year from a type of cancer called malignant mesothelioma that is associated with inhaling asbestos fibers, even briefly or in small amounts. Even after decades of regulation, between 1999 and 2015 there were 45,221 mesothelioma deaths in the U.S. The majority of those who died were men.

The greatest increase is among people over 85 years old, who were likely exposed to asbestos many years ago. It can take anywhere from two to seven decades for mesothelioma to develop after a person inhales asbestos fibers. And early deaths among people 35 to 65 are down overall.

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Source: Asbestos Deaths Remain A Public Health Problem


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FTY720 inhibits mesothelioma growth in vitro and in a syngeneic mouse model

Background  Malignant mesothelioma (MM) is a very aggressive type of cancer, with a dismal prognosis and inherent resistance to chemotherapeutics. Development and evaluation of new therapeutic approaches is highly needed. Immunosuppressant FTY720, approved for multiple sclerosis treatment, has recently raised attention for its anti-tumor activity in a variety of cancers. However, its therapeutic potential in MM has not been evaluated yet.

Methods  Cell viability and anchorage–independent growth were evaluated in a panel of MM cell lines and human mesothelial cells (HM) upon FTY720 treatment to assess in vitro anti-tumor efficacy. The mechanism of action of FTY720 in MM was assessed by measuring the activity of phosphatase protein 2A (PP2A)—a major target of FTY720….

Conclusions  Our preclinical data indicate that FTY720 is a potentially promising therapeutic agent for MM treatment.

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Source: FTY720 inhibits mesothelioma growth in vitro and in a syngeneic mouse model


 Mesothelioma, Asbestos, and Legal Compensation: Basic Facts

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Malignant mesothelioma due to asbestos exposure in dental tape

Although most cases of malignant mesothelioma of the pleura are caused by one or more readily recognized sources of exposure to asbestos, cases of the disease with more occult exposure occur, especially since asbestos has been used in over 3,000 products. Dental lining tape contained asbestos from the 1930s until at least the 1970s and was used in the lost wax method of casting crowns, bridges, and other metal dental prosthetic devices. We report six cases of pathology-verified malignant mesothelioma, mostly among dentists, following exposure to airborne dust from asbestos dental tape, which resulted in asbestos tort litigation. According to evidence available at present, chrysotile asbestos was the type of asbestos used in dental tape in the past in the United States, and the described cases followed relatively brief and intermittent exposure to this type of asbestos. These cases underscore the need for comprehensive exposure histories to determine exposure scenarios.

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Source: Malignant mesothelioma due to asbestos exposure in dental tape


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Clinical Safety and Activity of Pembrolizumab in Patients With Malignant Pleural Mesothelioma

BACKGROUND  Malignant pleural mesothelioma is a highly aggressive cancer with poor prognosis and few treatment options following progression on platinum-containing chemotherapy. We assessed the safety and efficacy of pembrolizumab (an anti-programmed cell death receptor 1 [PD-1] antibody) in advanced solid tumours expressing programmed cell death ligand 1 (PD-L1) and report here on the interim analysis of the malignant pleural mesothelioma cohort.

METHODS  Previously treated patients with PD-L1-positive malignant pleural mesothelioma were enrolled from 13 centres in six countries. Patients received pembrolizumab (10 mg/kg every 2 weeks) for up to 2 years or until confirmed progression or unacceptable toxicity….

FINDINGS  As of June 20, 2016, 25 patients received pembrolizumab. 16 (64%) patients reported a treatment-related adverse event; the most common adverse event were fatigue (six [24%]), nausea (six [24%]), and arthralgia (five [20%])….

INTERPRETATION  Pembrolizumab appears to be well tolerated and might confer anti-tumour activity in patients with PD-L1-positive malignant pleural mesothelioma. Response durability and efficacy in this patient population warrants further investigation.

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Source: Clinical Safety and Activity of Pembrolizumab in Patients With Malignant Pleural Mesothelioma


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Asbestos Case Beats Statute of Limitations

A federal judge has denied a pump manufacturer’s argument that an asbestos-related lung cancer case should be tossed because it wasn’t filed in time.

As asbestos litigation continues its steady decline and fewer lawsuits against companies for asbestos-related illnesses make it past the early stages of litigation, plaintiff Kathleen Conneen’s case on behalf of her deceased husband, Joseph Conneen, has cleared a significant hurdle.

U.S. District Judge Eduardo C. Robreno of the Eastern District of Pennsylvania denied defendant Goulds Pumps Inc.’s motion for summary judgment based on Pennsylvania’s two-year statute of limitations in asbestos cases, and under maritime law. Joseph Conneen worked in a shipyard.

The primary dispute centers on when Kathleen Conneen’s husband learned his exposure to asbestos could have been a factor in his diagnosis. According to Robreno’s opinion, Joseph Conneen, who filed suit in January 2015, was diagnosed with lung cancer in December of 2012.

Kathleen Conneen argued that her husband did not learn that asbestos exposure was a possible factor until February 2013, while Goulds countered that since Conneen’s husband worked around asbestos for 28 years and never smoked, he should have been more diligent in trying to identify the cause of his cancer.

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Source: Asbestos Case Beats Statute of Limitations

 


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