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


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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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Arizona High Court to Rule on Liability in Asbestos Take Home Exposure Case

The Arizona Supreme Court has agreed to consider whether employers can be held liable to somebody who contracted cancer from asbestos brought home on a parent’s work clothes.

The case stems from the 2014 death of Dr. Ernest Quiroz, whose 2013 negligence lawsuit contends he was exposed to asbestos on his father’s work clothes.

The facts as outlined in the appeal indicate he lived with his father from 1952 to 1966, during the time his father worked at Reynolds Metal Co. Dr. Quiroz lived in California until 1976 and in Michigan until his death in 2014. The suit alleges Dr. Quiroz contracted mesothelioma as a result of the exposure to his father’s work clothes.

The suit argues that Reynolds Metal Co. was legally obligated to avoid creating hazardous conditions that would injure people off its property.

Reynolds won a pretrial ruling by a trial judge, and the Court of Appeals upheld it.

The Court of Appeals said potential drawbacks of recognizing what’s called a duty of care in so-called “take-home exposure” cases outweigh potential benefits, partly by opening the door to liability claims involving an array of hazardous materials.

Source: Arizona High Court to Rule on Liability in Asbestos Take Home Exposure Case

 


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Patient-Derived Xenograft Establishment from Human Malignant Pleural Mesothelioma

Purpose: Malignant pleural mesothelioma (MPM) is a rare but aggressive disease with few therapeutic options. The tumor–stromal interface is important in MPM, but this is lost in cell lines, the main model used for preclinical studies. We sought to characterize MPM patient-derived xenografts (PDX) to determine their suitability as preclinical models and whether tumors that engraft reflect a more aggressive biological phenotype.

Experimental Design: Fresh tumors were harvested from extrapleural pneumonectomy, decortication, or biopsy samples of 50 MPM patients and implanted subcutaneously into immunodeficient mice and serially passaged for up to five generations. We correlated selected mesothelioma biomarkers between PDX and patient tumors, and PDX establishment with the clinical pathologic features of the patients, including their survival. DNA of nine PDXs was profiled using the OncoScan FFPE Express platform. Ten PDXs were treated with cisplatin and pemetrexed.

Results: A PDX was formed in 20 of 50 (40%) tumors implanted. Histologically, PDX models closely resembled the parent tumor. PDX models formed despite preoperative chemotherapy and radiotherapy. In multivariable analysis, patients whose tumors formed a PDX had significantly poorer survival when the model was adjusted for preoperative treatment (HR, 2.46; 95% confidence interval, 1.1–5.52; P = 0.028). Among 10 models treated with cisplatin, seven demonstrated growth inhibition. Genomic abnormalities seen in nine PDX models were similar to that previously reported.

Conclusions: Patients whose tumors form PDX models have poorer clinical outcomes. MPM PDX tumors closely resemble the genotype and phenotype of parent tumors, making them valuable models for preclinical studies.

Source: Patient-Derived Xenograft Establishment from Human Malignant Pleural Mesothelioma


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Diagnostic and Prognostic Biomarkers in the Rational Assessment of Mesothelioma (DIAPHRAGM) study: protocol of a prospective, multicentre, observational study

Malignant pleural mesothelioma (MPM) is an asbestos-related cancer, which is difficult to diagnose. Thoracoscopy is frequently required but is not widely available. An accurate, non-invasive diagnostic biomarker would allow early specialist referral, limit diagnostic delays and maximise clinical trial access. Current markers offer insufficient sensitivity and are not routinely used. The SOMAmer proteomic classifier and fibulin-3 have recently demonstrated sensitivity and specificity exceeding 90% in retrospective studies. DIAPHRAGM (Diagnostic and Prognostic Biomarkers in the Rational Assessment of Mesothelioma) is a suitably powered, multicentre, prospective observational study designed to determine whether these markers provide clinically useful diagnostic and prognostic information.

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Source: Diagnostic and Prognostic Biomarkers in the Rational Assessment of Mesothelioma (DIAPHRAGM) study: protocol of a prospective, multicentre, observational study


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Lung-sparing surgery may boost mesothelioma survival

Surgery that preserves the lung, when combined with other therapies, appears to extend the lives of people with a subtype of the rare and deadly cancer mesothelioma, a new study suggests.

Tracking 73 patients with advanced malignant pleural mesothelioma—which affects the lungs’ protective lining in the chest cavity—researchers found that those treated with lung-sparing had an average survival of nearly three years. A subset of those patients survived longer than seven years.

Mesothelioma patients treated with chemotherapy alone, which is standard care, live an average of 12 to 18 months, the researchers said.

Study participants received lung-sparing surgeries and another treatment called photodynamic therapy that uses light to kill cancer cells. Ninety-two percent of the group also received chemotherapy.

The study volunteers achieved far longer survival times, said study author Dr. Joseph Friedberg.

“When you take the [entire] lung out, it’s a significant compromise in quality of life,” said Friedberg. He’s director of the University of Maryland Medical Center’s Mesothelioma and Thoracic Oncology Treatment and Research Center in Baltimore.

“For all intents and purposes, this [lung-sparing surgical approach] is the largest palliative operation known to man, since chances of curing mesothelioma are vanishingly small,” said Friedberg. He completed the research while at his previous post at the University of Pennsylvania.

“Plus, most of these patients are elderly, so preserving quality of life was really the goal,” he added.

[Article continues at original source]

Source: Lung-sparing surgery may boost mesothelioma survival


 

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