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Rare Mesothelioma Type Linked to In-Dwelling Shunts – MedPage Today

KISSIMMEE, Fla. Cases of a rare peritoneal form of mesothelioma, distinct from the more familiar pleural version, appeared to stem from long-term in-dwelling shunts used to relieve pressure from the brain or other organs, researchers reported here.

In the small study, five of the seven patients had no association with common risk factors for mesothelioma radiation or asbestos contact, reported Tala Mujahed, BS, a medical student at the Mayo Clinic in Scottsdale, Arizona, at her poster presentation during the annual meeting of the College of American Pathologists.

"Asbestos exposure is considered the main risk factor for development of mesothelioma, but only 50% to 70% of patients report that asbestos exposure and other factors can play a role in some causes such as radiation, chronic inflammation, or chronic irritation of serous membranes," Mujahed told MedPage Today. "We are describing a series of young adult patients with long-standing in-dwelling shunt catheters who developed peritoneal mesothelioma, suggesting a novel association."

In her study, she reported that seven patients were seen by Mayo doctors, including six who had in-dwelling ventriculoperitoneal shunts -- brain to abdomen -- placed to control hydrocephalus, and one patient who had a porto-atrial shunt implanted to drain ascites. One of the hydrocephalus patients was not discussed as to outcomes because of exposure to asbestos and involvement in asbestos-related litigation, Mujahed explained.

"The six patients we are reporting on basically have nothing in common other than having these long-term in-dwelling shunts, and all of them developed this super-rare tumor," she explained. "Mesothelioma is usually associated with disease in the chest, although it can occur in the abdomen. They presented with swelling in the abdomen; some reported pain. They underwent imaging, and eventually a biopsy was taken. All were found to have this same tumor, and all had the biomarkers we can stain for and we would expect to see in this disease."

In the patients for whom complete data was available, shunts had been placed for a mean duration of 21 years, including one patient who had lived with a shunt for 35 years before developing mesothelioma.

Outcomes after diagnosis were dismal, with mean survival of only 8.7 months, Mujahed noted. "Some of these cases were referred to us after other institutions attempted to determine the cause of symptoms, so these patients had extensive disease when we were able to make a diagnosis. One of the reasons we wanted to present this study was to alert clinicians that in patients with in-dwelling shunts who had symptoms of mesothelioma [there] could be an unexpected complication."

Mujahed said that because of the low numbers in the study, she and her colleagues were not able to say definitively that irritation from the shunts was responsible for the cancer -- "but we know that chronic irritation in general is not the best thing and can lead to cancer in some cases," she said.

Asked for her perspective, Kisha Mitchell Richards, MD, medical director of pathology at Yale New Haven Health Greenwich Hospital in Connecticut, who was not affiliated with the study, said: "This is a fascinating study because peritoneal mesothelioma doesn't have a strong association with asbestos, but in these cases it appears that the cause may be long-standing irritation with these shunts. I am not aware of this connection between shunts and mesothelioma arising in the belly as have been previously reported."

"It is probably due to irritation of the device over the long-term," she told MedPage Today. "I do know there are many types of cancer that can arise due to inflammation. It happens all over the gut."

Regarding the clinical implications of the study, Mujahed said, "If a person has increased pressure in the brain, you are not going to not put in a shunt in fear that 30 years down the road there could be a rare cancer. But if a person does have a shunt and then develops symptoms that you as a doctor aren't sure what it is, they should consider it might be this rare disease. And if it is found early, then maybe there is something useful we can do for these people."

Mujahed and Richards disclosed no relevant relationships with industry.

2019-09-24T15:30:00-0400

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Rare Mesothelioma Type Linked to In-Dwelling Shunts - MedPage Today

Disappointment Over Immunotherapy in Mesothelioma – Medscape

BARCELONA Despite showing promise in phase 2 trials, new results from a randomized phase 3 trial are disappointing in a tumor type that remains a major killer.

In patients with malignant pleural mesothelioma (MPM) who had progressed after first-line chemotherapy, immunotherapy with pembrolizumab (Keytruda, Merck) appears to offer no survival advantages over standard chemotherapy.

The results come from the PROMISE-meso study, presented here at the European Society of Medical Oncology (ESMO) annual meeting.

Despite "nearly four times more patients" responding to immunotherapy than standard chemotherapy, "unfortunately these responses did not delay progression or improve survival," noted study investigator Sanjay Popat, MD, PhD, thoracic medical oncologist, Royal Marsden Hospital NHS Foundation Trust, London, England.

However, while pembrolizumab "was not superior to chemotherapy, survival was similar, and so pembrolizumab may represent an alternative."

He highlighted that, as in other immunotherapy trials in other cancer types, some of the mesothelioma patients had long responses, which suggests that some patients could "preferentially receive this treatment over chemotherapy."

Popat also suggested that, learning a lesson from lung cancer trials, combining immunotherapy with chemotherapy could have a beneficial effect.

"I would advise clinicians to enroll their patients into one of the large ongoing trials of first-line combination treatment so we can get answers as soon as possible about how to improve mesothelioma treatment," he said.

Commenting for ESMO, Federica Grosso, MD, from the Mesothelioma and Rare Cancers Unit at the Azienda Ospedaliera Nazionale SS Antonio e Biagio e Cesare Arrigo in Alessandria, Italy, said: "Although we did not see better survival with immunotherapy . . . the responses are encouraging."

Grosso explained that treatment of mesothelioma is limited, with the only approved regimen being the combination of pemetrexed and platinum derivatives. Patients generally die within 2 years of diagnosis.

There is currently no standard effective second line therapy for patients with mesothelioma. Those who respond well to pemetrexed- and platinum-based chemotherapy may be given a repeat course, while others are usually offered drugs such as gemcitabine/vinorelbine with response rates of approximately 10%.

Study discussant Nicolas Girard, MD, PhD, Curie-Montsouris Thorax Institute, Institut Curie, Paris, France, said that, overall, the results were "disappointing" despite being in line with findings seen with immunotherapy in phase 2 trials.

Putting the study in context, Girard said that MPM is a rare thoracic malignancy "that is aggressive and difficult to treat."

He noted that the majority of patients are diagnosed with advanced disease, with a median overall survival ranging from 12 to 20 months, and that patients with a nonepithelioid histologic subtype of tumor have a worse outcome.

"Given the aggressiveness of the disease and the absence of standard of care after the failure of platinum-based chemotherapy, immune checkpoint inhibitors represent a new avenue," Girard continued.

He noted that several phase 2, noncomparative trials with immunotherapy using pembrolizumab, nivolumab (Opdivo, Bristol-Myers Squibb), or avelumab (Bavencio, Merck and Pfizer) have reported response rates of between 20% and 30%, and disease control rates of 50% to 60%.

Median progression-free survival (PFS) in these trials has ranged from 3 to 5 months, giving overall survival rates in the second- to third-line setting of between 7 to 18 months.

For comparison, the new results from the PROMISE-meso trial show a median PFS of 2.5 months with pembrolizumab and just under 3.5 months with chemotherapy. Overall survival was a median of 10.7 months with pembrolizumab and 11.7 months for chemotherapy (P = .85).

Girard noted that the majority of guidelines do not currently recommend the checkpoint inhibitors in second-line or relapsed settings.

However, the latest National Comprehensive Cancer Network guidelines do suggest pembrolizumab monotherapy or nivolumab with or without ipilimumab (Yervoy, Bristol-Myers Squibb) as among the potential treatment options following first-line chemotherapy.

The PROMISE-meso study recruited a total of 144 patients with MSM between September 2017 and August 2018 in the United Kingdom, Switzerland, and Spain. Accrual was faster than expected, which Girard noted speaks to the high unmet clinical need for this disease.

The median age of the patients was between 69 and 71 years, and between 79.4% and 84.5% were male.

The vast majority of patients (87.3% - 90.4%) had epithelioid tumors, and between 61.7% and 76.1% had a good European Organisation for Research and Treatment of Cancer (EORTC) prognostic score.

At 6 months, 25.0% of pembrolizumab patients and 27.4% of those in the chemotherapy arm were progression-free, and 68.5% and 72.9%, respectively, were still alive.

Subgroup analysis did not reveal any patients who benefited significantly from one treatment over another, although those with nonepithelioid tumors appeared to fare better with chemotherapy than immunotherapy.

The overall response rate was higher among patients given pembrolizumab than in those treated with chemotherapy, at 22% vs 6% (P = .004), which appeared to be driven by a larger number of patients experiencing a partial response, at 21.9% vs 5.6%.

Surprisingly, the median duration of response with immunotherapy was far shorter for pembrolizumab, at 4.6 months vs 11.2 months for chemotherapy, although this difference was not significant and Popat pointed out that this was due to one chemotherapy patient being an outlier in terms of response duration.

Using predefined cutoffs of 0%, 1%, and 50%, the team were not able to identify a subgroup of patients in terms of their PD-L1 expression who performed better with pembrolizumab or chemotherapy.

This was underlined by a time-to-treatment failure analysis, which showed no significant difference between the two treatment groups, regardless of PD-L1 status.

Treatment-related adverse events were similarly frequent in pembrolizumab- and chemotherapy-treated patients, at 69.4% vs 72.9% overall and 19.4% vs 24.3% for grade 3 to 5 events.

Popat noted that nausea, constipation, oral mucositis, and decreased neutrophil count were significantly more common with chemotherapy treatment than with pembrolizumab, while pruritus, dry skin, and maculopapular rash were significantly more frequent with immunotherapy.

Girard said that, overall, the overall response rates and disease control rates seen with pembrolizumab, as well as the PFS and overall survival results are, in fact, comparable to those seen in past in phase 2 studies with immunotherapy.

However, the lack of benefit relative to chemotherapy means that, "obviously, this is disappointing data for immune checkpoint inhibitors in a late-line setting."

He also added: "I'm not sure that we will be able, from these data, to identify a subset of patients for whom pembrolizumab would provide a long-term benefit."

ESMO notes that mesothelioma is a rare but fatal form of thoracic cancer that is diagnosed in more than 30,000 people per year and kills over 25,000. Most cases (> 80%) arise from exposure to asbestos fibers that cause long-term inflammation in the mesothelial cells of the lung, slowly leading to cancerous changes 20 to 50 years later.

The incidence of mesothelioma has fallen in Australia, the United States, and Western Europe where asbestos or strict regulations were introduced in the 1970s and 1980s. Deaths in the United States have gradually decreased compared with Western Europe, where mortality is relatively stable. However, deaths in Eastern Europe appear to be rising, possibly due to later asbestos bans, and rates are also rising in Japan due to historical asbestos imports.

"The worldwide number of deaths is expected to rise as people exposed to asbestos before it was banned continue to be diagnosed many years later," commented ESMO expert Grosso, who is from Italy.

She noted that there are certain "hotspots" for the disease, for example, at Casale Monferrato in Italy "which had the largest asbestos plant in the world until it was closed in 1987. In a population of 35,000, there are approximately 50 cases per year an incidence more than 20 times higher than in the rest of the country."

"Mesothelioma is a huge problem because asbestos powder from the plants pollutes large areas. It isn't just people who worked in the plant who are being diagnosed, it is their families and unrelated people, some of whom are only 40 to 50 years old much younger than we would expect to see with mesothelioma," she pointed out.

"A similar situation of environmental exposure was recently reported in Sibat [Colombia] where a plant was closed only a few years ago and many cases of mesothelioma are being diagnosed," she added.

"Unfortunately, we can expect to see an increase in mesothelioma in countries where asbestos is still used for many years to come," she added.

The study was funded by MSD, manufacturer of pembrolizumab. Popat reports relationships with Boehringer Ingelheim, Epizyme, BMS, Clovis Oncology, Roche, Lilly, Takeda, AstraZeneca, Chugai, Novartis, Pfizer, Merck Sharp & Dohme, Guardant Health, and Abbvie. Girard reports relationships with Astra-Zeneca, Boehringer-Ingelheim, Bristol Myers Squibb, Hoffmann La Roche, Lilly, Merck Sharp Dohme, Novartis, Pfizer, Pharmamar, Takeda and Trizell.

ESMO Congress 2019: Abstract LBA91_PR. Presented September 30, 2019.

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Disappointment Over Immunotherapy in Mesothelioma - Medscape

Mesothelioma Compensation Center Now Has Endorsed the Attorney Erik Karst of the Law Firm of Karst von Oiste and Erik For a Nuclear Power Worker or…

NEW YORK, Sept. 25, 2019 /PRNewswire/ -- The Mesothelioma Compensation Center is the only group in the nation that specializes in assisting nuclear power plant workers or Nuclear Navy Veterans who have been diagnosed with mesothelioma and their number one goal is a person like this receives the very best possible financial compensation settlement. If a nuclear power worker or Nuclear Navy Veteran with mesothelioma or their family would call 800-714-0303, they can typically have the person talking directly with attorney Erik Karst of the law firm of Karst von Oiste within 20 or 30 minutes.

Erik Karst and his partner Doug von Oiste of the law firm of Karst von Oiste have obtained over a billion dollars in mesothelioma or asbestos exposure compensation settlements for their clients as the Mesothelioma Compensation Center would be happy to discuss anytime at 800-714-0303.www.karstvonoiste.com/

The Mesothelioma Compensation Center says, "The reason we mention nuclear plant workers and Nuclear Navy Veterans with mesothelioma so frequently is because many nuclear power plant workers received their initial training about reactors in the US Navy. The US Navy literally has a school where navy sailors learn about nuclear reactors and it is called 'Nuke School.'"http://www.navy.mil/search/display.asp?story_id=79643.

According to the Mesothelioma Compensation Center, "The reason we have recommended the law firm of Karst von Oiste and their founding partner Erik Karst of Karst von Oiste is they work their mesothelioma compensation claims extremely hard and they typically get the best financial compensation results for their clients on a nationwide basis. A case work-up typically involves every single place or instance where a diagnosed person could have been exposed to asbestos. Further, there is no charge for their services if there is not a financial settlement as we would be happy to explain anytime at 800-714-0303." https://MesotheliomaCompensationCenter.Com

Before a nuclear power worker or Nuclear Navy Veteran with mesothelioma or their family hires a law firm they are urged to call the Mesothelioma Compensation Center anytime at 800-714-0303.The potential compensation for a nuclear power worker or Nuclear Navy Veteran with mesothelioma could easily exceed a million dollars provided they have the best legal representation."https://MesotheliomaCompensationCenter.Com

The Mesothelioma Compensation Center specializes in assisting specific types of people who have been diagnosed with mesothelioma. The Center's top priority is assisting US Navy Veterans, shipyard workers, oil refinery workers, public-utility workers, chemical plant workers, manufacturing workers, power plant workers, plumbers, welders, electricians, millwrights, pipefitters, boiler technicians, machinists, nuclear power plant workers, hydro-electric workers or oil and gas field production workers who have been diagnosed with this rare cancer caused by asbestos exposure. In most instances a diagnosed person with mesothelioma was exposed to asbestos in the 1950's, 1960's, 1970's, or 1980's.https://MesotheliomaCompensationCenter.Com

According to the CDC the states indicated with the highest incidence of mesothelioma includeMaine,Massachusetts,Connecticut,Maryland,New Jersey,Pennsylvania,Ohio,West Virginia,Virginia,Michigan,Illinois,Minnesota,Louisiana,Washington, andOregon.

However, a Nuclear Navy Veteran or a nuclear power worker with mesothelioma could live in any state including California, New York, Florida, Texas, Illinois, Kentucky, Tennessee, Mississippi, Georgia, Alabama, Wyoming, Colorado, New Mexico, Nevada, Utah, Arizona, Idaho, or Alaska. http://www.karstvonoiste.com/

For more information about mesothelioma please refer to the National Institutes of Health's web site related to this rare form of cancer:https://www.cancer.gov/types/mesothelioma.

Media Contact:

Michael Thomas800-714-0303220569@email4pr.com

SOURCE Mesothelioma Compensation Center

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Mesothelioma Compensation Center Now Has Endorsed the Attorney Erik Karst of the Law Firm of Karst von Oiste and Erik For a Nuclear Power Worker or...

Mesothelioma Victims Center Now Offers a Navy Veteran with Mesothelioma Direct Access to Attorney Erik Karst of Karst von Oiste to Answer Specific…

NEW YORK, Oct. 1, 2019 /PRNewswire/ -- The Mesothelioma Victims Center says, "If a Navy Veteran with recently diagnosed mesothelioma or their family members would call us at 800-714-0303 we will provide them with direct access to attorney Erik Karst of the law firm of Karst von Oiste to discuss compensation, how the claims process works and what things they will need to create the environment for the best possible compensation results." Erik Karst and his partner Doug von Oiste are responsible for over a billion dollars in mesothelioma or asbestos exposure financial compensation results. Trust us-talking directly with attorney Erik Karst is a much better option than ordering a 'free' book about mesothelioma or calling some claims center.

"We have recommended attorney Erik Karst and his colleagues at the law firm of Karst von Oiste for a US Navy Veteran with mesothelioma-becausethey share our passion about making certain a Navy Veteran with mesothelioma or their family members receive the best possible financial compensation results as we would like to discuss anytime at 800-714-0303." http://www.karstvonoiste.com

Out of fear most US Navy Veterans or people with mesothelioma will not get properly compensated. The Mesothelioma Victims Center is offering to assist a Navy Veteran or a person with this rare cancer or their family to build out what they refer to as the list. The 'list' documents how, where, and when a person with mesothelioma was exposed to asbestos. It is this vital information that becomes the foundation for a mesothelioma compensation claim as the group would be happy to discuss anytime at 800-714-0303. https://MesotheliomaVictimsCenter.Com

Example of an asbestos exposure how, where and when addition to the list : In January of 1974 I was assigned to a navy destroyer as a boiler technician. My duties included maintaining the boilers, cleaning valves, replacing gaskets, replacing insulation, rebuilding pumps.

The Mesothelioma Victims Center says, "We would turn this type of information over to the lawyers at the law firm of Karst von Oiste who will determine who made these boilers, valves, gaskets, insulation and pumps. Most would have contained asbestos as we'd like to explain at 800-714-0303." https://MesotheliomaVictimsCenter.Com

Mesothelioma is a rare form of cancer caused by exposure to asbestos. High risk work groups for exposure to asbestos include Veterans of the US Navy, power plant workers, shipyard workers, oil refinery workers, steel mill workers, miners, pulp or paper mill workers, printers, factory workers, railroad workers, plumbers, electricians, auto mechanics, machinists, welders, pipefitters, insulators, firemen and construction workers. In most instances a person who has been diagnosed with mesothelioma was exposed to asbestos in the 1950's, 1960's, 1970's, or 1980's. https://MesotheliomaVictimsCenter.Com

According to the CDC the states indicated with the highest incidence of mesothelioma include Maine, Massachusetts, Connecticut, Maryland, New Jersey, Pennsylvania, Ohio, West Virginia, Virginia, Michigan, Illinois, Minnesota, Louisiana, Washington, and Oregon. However, based on the calls the Mesothelioma Victims Center receives a former auto or truck factory or manufacturing worker with mesothelioma or asbestos exposure lung cancer could live in any state including New York, Florida, California, Texas, Iowa, Indiana, Missouri, North Carolina, Kentucky, Tennessee, Georgia, Alabama, Oklahoma, Arkansas, Kansas, Nebraska, North Dakota, Wyoming, Nevada, Colorado, New Mexico, Utah, Arizona, Idaho, or Alaska. http://www.karstvonoiste.com/

For more information about mesothelioma please refer to the National Institutes of Health's web site related to this rare form of cancer: https://www.cancer.gov/types/mesothelioma.

Contact: Michael Thomas 800-714-0303 220926@email4pr.com

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Jury awards $40.3 million in talcum powder trial | Around The State – Antelope Valley Press

LOS ANGELES (CNS) A woman who alleged that she acquired mesothelioma from her use of Johnson & Johnson talcum powder was awarded $40.3 million by a Los Angeles jury, her attorneys said today.

The Los Angeles Superior Court panel deliberated for six days before reaching its verdict Friday in the lawsuit brought by Nancy Cabibi and her husband Phil, both 71 years old. She was diagnosed with mesothelioma in 2017 and has undergone surgery, chemotherapy, radiation and immunotherapy, according to her court papers.

Testing of her body tissue showed the presence of tremolite and anthophyllite asbestos, known contaminants of Johnsons Baby Powder and Shower to Shower, both of which were manufactured by Johnson & Johnson and both of which Nancy Cabibi used, according to her court papers.

The jury found Johnsons Baby Powder defective because it contained asbestos, according to her attorneys. The panel also found the powder caused her mesothelioma, which is an invariably fatal form of cancer, her attorneys said.

Johnson & Johnson attorneys argued Cabibi was exposed to asbestos through living in an industrial area of Los Angeles. Her lawyers countered that she never worked in or even entered any facilities where she would have been exposed to asbestos. The couple now lives in Idaho.

Nancy Cabibi is fighting to survive every single day because of asbestos in Johnsons Baby Powder, said plaintiffs attorney David Greenstone. While we are very pleased with this verdict, we know that we must continue to fight on behalf of the Cabibis and so many others who have beenharmed.

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Jury awards $40.3 million in talcum powder trial | Around The State - Antelope Valley Press

Judge Rejects J&J’s Bid to Avoid Paying Award to Deceased Mesothelioma Victim – Mesothelioma.net Blog

Last June, a jury in California found Johnson & Johnson, Colgate-Palmolive and Avon Products jointly liable for Patricia Schmitzs malignant mesothelioma, and awarded the woman $2 million in economic damages and another $10 million in noneconomic damages. One month later Mrs. Schmitz succumbed to her cancer, and in response Johnson & Johnson and Colgate-Palmolive filed motions for the court to vacate the portion of her verdict created to address her pain and suffering and to open a new trial to reheat the evidence. Alameda Superior Court Judge Frank Roesch has denied both Johnson & Johnsons request regarding the compensation and Colgate-Palmolives request for a new trial.

In a remarkably cynical legal move, Johnson & Johnson argued that because Mrs. Schmitz had died of her mesothelioma, she was no longer entitled to an award for pain and suffering. Their motion to set aside and vacate the judgment was denied.Colgate had also argued that the jurys verdict was not supported by the evidence presented at trial and requested a new trial, but the judge also denied this request.

The original jury verdict had assigned 40 percent of the blame for her death to Colgate-Palmolive, Johnson & Johnson and their subsidiary Johnson a& Johnson Consumer Inc. 40 percent responsible, and Avon 20 percent responsible, despite the fact that the company had successfully avoided being named as a defendant in the trial due to the fact that the California court had no jurisdiction over them.

In addition to trying to negate the jurys verdict on pain and suffering, the companies also filed motions to void having to pay the mesothelioma victims litigation costs. Johnson & Johnson had been assigned to pay some of the costs that its lawyers say belonged to Colgate and Avon, but the judge rejected that request as well, saying that Mrs. Schmitz couldnt only sue Johnson & Johnson because she had used products from all three companies, and that her costs were attributable to the whole case.

Asbestos companies fight against having to pay mesothelioma victims at every step, but there are resources available to protect their rights. For more information, contact the Patient Advocates at Mesothelioma.net today at 1-800-692-8608.

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Judge Rejects J&J's Bid to Avoid Paying Award to Deceased Mesothelioma Victim - Mesothelioma.net Blog

Mesothelioma – Wikipedia

Cancer associated with asbestos

Mesothelioma is a type of cancer that develops from the thin layer of tissue that covers many of the internal organs (known as the mesothelium).[9] The most common area affected is the lining of the lungs and chest wall.[1][3] Less commonly the lining of the abdomen and rarely the sac surrounding the heart,[10] or the sac surrounding the testis may be affected.[1][11] Signs and symptoms of mesothelioma may include shortness of breath due to fluid around the lung, a swollen abdomen, chest wall pain, cough, feeling tired, and weight loss.[1] These symptoms typically come on slowly.[2]

More than 80% of mesothelioma cases are caused by exposure to asbestos.[3] The greater the exposure the greater the risk.[3] As of 2013, about 125 million people worldwide have been exposed to asbestos at work.[12] High rates of disease occur in people who mine asbestos, produce products from asbestos, work with asbestos products, live with asbestos workers, or work in buildings containing asbestos.[3] Asbestos exposure and the onset of cancer are generally separated by about 40 years.[3] Washing the clothing of someone who worked with asbestos also increases the risk.[12] Other risk factors include genetics and infection with the simian virus 40.[3] The diagnosis may be suspected based on chest X-ray and CT scan findings, and is confirmed by either examining fluid produced by the cancer or by a tissue biopsy of the cancer.[2]

Prevention centers around reducing exposure to asbestos.[4] Treatment often includes surgery, radiation therapy, and chemotherapy.[5] A procedure known as pleurodesis, which involves using substances such as talc to scar together the pleura, may be used to prevent more fluid from building up around the lungs.[5] Chemotherapy often includes the medications cisplatin and pemetrexed.[2] The percentage of people that survive five years following diagnosis is on average 8% in the United States.[6]

In 2015, about 60,800 people had mesothelioma, and 32,000 died from the disease.[7][8] Rates of mesothelioma vary in different areas of the world.[3] Rates are higher in Australia, the United Kingdom, and lower in Japan.[3] It occurs in about 3,000 people per year in the United States.[13] It occurs more often in males than females.[3] Rates of disease have increased since the 1950s.[3] Diagnosis typically occurs after the age of 65 and most deaths occur around 70 years old.[3] The disease was rare before the commercial use of asbestos.[3]

Symptoms or signs of mesothelioma may not appear until 20 to 50 years (or more) after exposure to asbestos. Shortness of breath, cough, and pain in the chest due to an accumulation of fluid in the pleural space (pleural effusion) are often symptoms of pleural mesothelioma.[14]

Mesothelioma that affects the pleura can cause these signs and symptoms:[14]

In severe cases, the person may have many tumor masses. The individual may develop a pneumothorax, or collapse of the lung. The disease may metastasize, or spread to other parts of the body.

The most common symptoms of peritoneal mesothelioma are abdominal swelling and pain due to ascites (a buildup of fluid in the abdominal cavity). Other features may include weight loss, fever, night sweats, poor appetite, vomiting, constipation, and umbilical hernia.[15] If the cancer has spread beyond the mesothelium to other parts of the body, symptoms may include pain, trouble swallowing, or swelling of the neck or face.[citation needed]These symptoms may be caused by mesothelioma or by other, less serious conditions.

Tumors that affect the abdominal cavity often do not cause symptoms until they are at a late stage. Symptoms include:[citation needed]

Pericardial mesothelioma is not well characterized, but observed cases have included cardiac symptoms, specifically constrictive pericarditis, heart failure, pulmonary embolism, and cardiac tamponade. They have also included nonspecific symptoms, including substernal chest pain, orthopnea (shortness of breath when lying flat), and cough. These symptoms are caused by the tumor encasing or infiltrating the heart.[10]

In severe cases of the disease, the following signs and symptoms may be present:[citation needed]

If a mesothelioma forms metastases, these most commonly involve the liver, adrenal gland, kidney, or other lung.[16]

Working with asbestos is the most common risk factor for mesothelioma.[17] However, mesothelioma has been reported in some individuals without any known exposure to asbestos. Tentative evidence also raises concern about carbon-fibre nanotubes.[18][19]

The incidence of mesothelioma has been found to be higher in populations living near naturally occurring asbestos. People can be exposed to naturally occurring asbestos in areas where mining or road construction is occurring, or when the asbestos-containing rock is naturally weathered. Another common route of exposure is through asbestos-containing soil, which is used to whitewash, plaster, and roof houses in Greece.[12] In central Cappadocia, Turkey, mesothelioma was causing 50% of all deaths in three small villagesTuzky, Karain, and Sarhdr. Initially, this was attributed to erionite. Environmental exposure to asbestos has caused mesothelioma in places other than Turkey, including Corsica, Greece, Cyprus, China, and California.[12][20][21] In the northern Greek mountain town of Metsovo, this exposure had resulted in mesothelioma incidence around 300 times more than expected in asbestos-free populations, and was associated with very frequent pleural calcification known as "Metsovo Lung".[22][23]

The documented presence of asbestos fibers in water supplies and food products has fostered concerns about the possible impact of long-term and, as yet, unknown exposure of the general population to these fibers.[citation needed]

Exposure to talc is also a risk factor for mesothelioma; exposure can affect those who live near talc mines, work in talc mines, or work in talc mills.[24]

In the United States, asbestos is considered the major cause of malignant mesothelioma[25] and has been considered "indisputably"[26] associated with the development of mesothelioma. Indeed, the relationship between asbestos and mesothelioma is so strong that many consider mesothelioma a signal or sentinel tumor.[27][28][29][30] A history of asbestos exposure exists in most cases.

Pericardial mesothelioma may not be associated with asbestos exposure.[10]

Asbestos was known in antiquity, but it was not mined and widely used commercially until the late 19th century. Its use greatly increased during World War II. Since the early 1940s, millions of American workers have been exposed to asbestos dust. Initially, the risks associated with asbestos exposure were not publicly known. However, an increased risk of developing mesothelioma was later found among naval personnel (e.g., Navy, Marine Corps, and Coast Guard), shipyard workers, people who work in asbestos mines and mills, producers of asbestos products, workers in the heating and construction industries, and other tradespeople. Today, the official position of the U.S. Occupational Safety and Health Administration (OSHA) and the U.S. EPA is that protections and "permissible exposure limits" required by U.S. regulations, while adequate to prevent most asbestos-related non-malignant disease, are not adequate to prevent or protect against asbestos-related cancers such as mesothelioma.[31] Likewise, the British Government's Health and Safety Executive (HSE) states formally that any threshold for exposure to asbestos must be at a very low level and it is widely agreed that if any such threshold does exist at all, then it cannot currently be quantified. For practical purposes, therefore, HSE assumes that no such "safe" threshold exists. Others have noted as well that there is no evidence of a threshold level below which there is no risk of mesothelioma.[32] There appears to be a linear, doseresponse relationship, with increasing dose producing increasing risk of disease.[33] Nevertheless, mesothelioma may be related to brief, low level or indirect exposures to asbestos.[26] The dose necessary for effect appears to be lower for asbestos-induced mesothelioma than for pulmonary asbestosis or lung cancer.[26] Again, there is no known safe level of exposure to asbestos as it relates to increased risk of mesothelioma.

The time from first exposure to onset of the disease, is between 25 and 70 years.[34] It is virtually never less than fifteen years and peaks at 3040 years.[26][35] The duration of exposure to asbestos causing mesothelioma can be short. For example, cases of mesothelioma have been documented with only 13 months of exposure.[36][37]

Exposure to asbestos fibers has been recognized as an occupational health hazard since the early 20th century. Numerous epidemiological studies have associated occupational exposure to asbestos with the development of pleural plaques, diffuse pleural thickening, asbestosis, carcinoma of the lung and larynx, gastrointestinal tumors, and diffuse malignant mesothelioma of the pleura and peritoneum. Asbestos has been widely used in many industrial products, including cement, brake linings, gaskets, roof shingles, flooring products, textiles, and insulation.[38]

Commercial asbestos mining at Wittenoom, Western Australia, took place from 1937 to 1966. The first case of mesothelioma in the town occurred in 1960. The second case was in 1969, and new cases began to appear more frequently thereafter. The lag time between initial exposure to asbestos and the development of mesothelioma varied from 12 years 9 months up to 58 years.[39] A cohort study of miners employed at the mine reported that 85 deaths attributable to mesothelioma had occurred by 1985. By 1994, 539 reported deaths due to mesothelioma had been reported in Western Australia.[citation needed]

Occupational exposure to asbestos in the United States mainly occurs when people are maintaining buildings that already have asbestos. Approximately 1.3 million US workers are exposed to asbestos annually; in 2002, an estimated 44,000 miners were potentially exposed to asbestos.[24]

Family members and others living with asbestos workers have an increased risk of developing mesothelioma, and possibly other asbestos-related diseases.[11][40][41] This risk may be the result of exposure to asbestos dust brought home on the clothing and hair of asbestos workers via washing a worker's clothes or coming into contact with asbestos-contaminated work clothing.[12][24] To reduce the chance of exposing family members to asbestos fibres, asbestos workers are usually required to shower and change their clothing before leaving the workplace.[citation needed]

Many building materials used in both public and domestic premises prior to the banning of asbestos may contain asbestos. Those performing renovation works or DIY activities may expose themselves to asbestos dust. In the UK, use of chrysotile asbestos was banned at the end of 1999. Brown and blue asbestos were banned in the UK around 1985. Buildings built or renovated prior to these dates may contain asbestos materials.[citation needed]

In a recent research carried on white American population in 2012, it was found that people with a germline mutation in their BAP1 gene are at higher risk of developing mesothelioma and uveal melanoma.[42]

Erionite is a zeolite mineral with similar properties to asbestos and is known to cause mesothelioma.[11] Detailed epidemiological investigation has shown that erionite causes mesothelioma mostly in families with a genetic predisposition.[12][20][21] Erionite is found in deposits in the Western United States, where it is used in gravel for road surfacing, and in Turkey, where it is used to construct homes. In Turkey, the United States, and Mexico, erionite has been associated with mesothelioma and has thus been designated a "known human carcinogen" by the US National Toxicology Program.[21]

In rare cases, mesothelioma has also been associated with irradiation of the chest or abdomen, intrapleural thorium dioxide (thorotrast) as a contrast medium, and inhalation of other fibrous silicates, such as erionite or talc.[11][24] Some studies suggest that simian virus 40 (SV40) may act as a cofactor in the development of mesothelioma.[24] This has been confirmed in animal studies,[43][44] but studies in humans are inconclusive.[43][45][46]

The mesothelium consists of a single layer of flattened to cuboidal cells forming the epithelial lining of the serous cavities of the body including the peritoneal, pericardial and pleural cavities. Deposition of asbestos fibers in the parenchyma of the lung may result in the penetration of the visceral pleura from where the fiber can then be carried to the pleural surface, thus leading to the development of malignant mesothelial plaques. The processes leading to the development of peritoneal mesothelioma remain unresolved, although it has been proposed that asbestos fibers from the lung are transported to the abdomen and associated organs via the lymphatic system. Additionally, asbestos fibers may be deposited in the gut after ingestion of sputum contaminated with asbestos fibers.[citation needed]

Pleural contamination with asbestos or other mineral fibers has been shown to cause cancer. Long thin asbestos fibers (blue asbestos, amphibole fibers) are more potent carcinogens than "feathery fibers" (chrysotile or white asbestos fibers).[26] However, there is now evidence that smaller particles may be more dangerous than the larger fibers. They remain suspended in the air where they can be inhaled, and may penetrate more easily and deeper into the lungs. "We probably will find out a lot more about the health aspects of asbestos from [the World Trade Center attack], unfortunately," said Dr. Alan Fein, chief of pulmonary and critical-care medicine at North Shore-Long Island Jewish Health System.[47]

Mesothelioma development in rats has been demonstrated following intra-pleural inoculation of phosphorylated chrysotile fibers. It has been suggested that in humans, transport of fibers to the pleura is critical to the pathogenesis of mesothelioma. This is supported by the observed recruitment of significant numbers of macrophages and other cells of the immune system to localized lesions of accumulated asbestos fibers in the pleural and peritoneal cavities of rats. These lesions continued to attract and accumulate macrophages as the disease progressed, and cellular changes within the lesion culminated in a morphologically malignant tumor.[citation needed]

Experimental evidence suggests that asbestos acts as a complete carcinogen with the development of mesothelioma occurring in sequential stages of initiation and promotion. The molecular mechanisms underlying the malignant transformation of normal mesothelial cells by asbestos fibers remain unclear despite the demonstration of its oncogenic capabilities (see next-but-one paragraph). However, complete in vitro transformation of normal human mesothelial cells to a malignant phenotype following exposure to asbestos fibers has not yet been achieved. In general, asbestos fibers are thought to act through direct physical interactions with the cells of the mesothelium in conjunction with indirect effects following interaction with inflammatory cells such as macrophages.[citation needed]

Analysis of the interactions between asbestos fibers and DNA has shown that phagocytosed fibers are able to make contact with chromosomes, often adhering to the chromatin fibers or becoming entangled within the chromosome. This contact between the asbestos fiber and the chromosomes or structural proteins of the spindle apparatus can induce complex abnormalities. The most common abnormality is monosomy of chromosome 22. Other frequent abnormalities include structural rearrangement of 1p, 3p, 9p and 6q chromosome arms.[citation needed]

Common gene abnormalities in mesothelioma cell lines include deletion of the tumor suppressor genes:[citation needed]

Asbestos has also been shown to mediate the entry of foreign DNA into target cells. Incorporation of this foreign DNA may lead to mutations and oncogenesis by several possible mechanisms:

Several genes are commonly mutated in mesothelioma, and may be prognostic factors. These include epidermal growth factor receptor (EGFR) and C-Met, receptor tyrosine kinases which are overexpressed in many mesotheliomas. Some association has been found with EGFR and epithelioid histology but no clear association has been found between EGFR overexpression and overall survival. Expression of AXL receptor tyrosine kinase is a negative prognostic factor. Expression of PDGFRB is a positive prognostic factor.[49] In general, mesothelioma is characterized by loss of function in tumor suppressor genes, rather than by an overexpression or gain of function in oncogenes.[50]

As an environmentally triggered malignancy, mesothelioma tumors have been found to be polyclonal in origin, by performing a X-inactivation based assay on epitheloid and biphasic tumors obtained from female patients.[51] These results suggest that an environmental factor, most likely asbestos exposure, may damage and transform a group of cells in the tissue, resulting in a population of tumor cells that are, albeit only slightly, genetically different.[52]

Asbestos fibers have been shown to alter the function and secretory properties of macrophages, ultimately creating conditions which favour the development of mesothelioma. Following asbestos phagocytosis, macrophages generate increased amounts of hydroxyl radicals, which are normal by-products of cellular anaerobic metabolism. However, these free radicals are also known clastogenic (chromosome-breaking) and membrane-active agents thought to promote asbestos carcinogenicity. These oxidants can participate in the oncogenic process by directly and indirectly interacting with DNA, modifying membrane-associated cellular events, including oncogene activation and perturbation of cellular antioxidant defences.[citation needed]

Asbestos also may possess immunosuppressive properties. For example, chrysotile fibres have been shown to depress the in vitro proliferation of phytohemagglutinin-stimulated peripheral blood lymphocytes, suppress natural killer cell lysis and significantly reduce lymphokine-activated killer cell viability and recovery. Furthermore, genetic alterations in asbestos-activated macrophages may result in the release of potent mesothelial cell mitogens such as platelet-derived growth factor (PDGF) and transforming growth factor- (TGF-) which in turn, may induce the chronic stimulation and proliferation of mesothelial cells after injury by asbestos fibres.[citation needed]

Diagnosis of mesothelioma can be suspected with imaging but is confirmed with biopsy. It must be clinically and histologically differentiated from other pleural and pulmonary malignancies, including reactive pleural disease, primary lung carcinoma, pleural metastases of other cancers, and other primary pleural cancers.[11]Primary pericardial mesothelioma is often diagnosed after it has metastasized to lymph nodes or the lungs.[10]

Diagnosing mesothelioma is often difficult because the symptoms are similar to those of a number of other conditions. Diagnosis begins with a review of the patient's medical history. A history of exposure to asbestos may increase clinical suspicion for mesothelioma. A physical examination is performed, followed by chest X-ray and often lung function tests. The X-ray may reveal pleural thickening commonly seen after asbestos exposure and increases suspicion of mesothelioma.[14] A CT (or CAT) scan or an MRI is usually performed. If a large amount of fluid is present, abnormal cells may be detected by cytopathology if this fluid is aspirated with a syringe.[10] For pleural fluid, this is done by thoracentesis or tube thoracostomy (chest tube); for ascites, with paracentesis or ascitic drain; and for pericardial effusion with pericardiocentesis. While absence of malignant cells on cytology does not completely exclude mesothelioma, it makes it much more unlikely, especially if an alternative diagnosis can be made (e.g., tuberculosis, heart failure).[citation needed] However, with primary pericardial mesothelioma, pericardial fluid may not contain malignant cells and a tissue biopsy is more useful in diagnosis.[10] Using conventional cytology diagnosis of malignant mesothelioma is difficult, but immunohistochemistry has greatly enhanced the accuracy of cytology.[citation needed]

Generally, a biopsy is needed to confirm a diagnosis of malignant mesothelioma. A doctor removes a sample of tissue for examination under a microscope by a pathologist. A biopsy may be done in different ways, depending on where the abnormal area is located. If the cancer is in the chest, the doctor may perform a thoracoscopy. In this procedure, the doctor makes a small cut through the chest wall and puts a thin, lighted tube called a thoracoscope into the chest between two ribs. Thoracoscopy allows the doctor to look inside the chest and obtain tissue samples. Alternatively, the chest surgeon might directly open the chest (thoracotomy). If the cancer is in the abdomen, the doctor may perform a laparoscopy. To obtain tissue for examination, the doctor makes a small incision in the abdomen and inserts a special instrument into the abdominal cavity. If these procedures do not yield enough tissue, an open surgical procedure may be necessary.[citation needed]

Immunohistochemical studies play an important role for the pathologist in differentiating malignant mesothelioma from neoplastic mimics, such as breast or lung cancer that has metastasized to the pleura. There are numerous tests and panels available, but no single test is perfect for distinguishing mesothelioma from carcinoma or even benign versus malignant. The positive markers indicate that mesothelioma is present; if other markers are positive it may indicate another type of cancer, such as breast or lung adenocarcinoma. Calretinin is a particularly important marker in distinguishing mesothelioma from metastatic breast or lung cancer.[11]

There are three main histological subtypes of malignant mesothelioma: epithelioid, sarcomatous, and biphasic. Epithelioid and biphasic mesothelioma make up approximately 75-95% of mesotheliomas and have been well characterized histologically, whereas sarcomatous mesothelioma has not been studied extensively. Most mesotheliomas express high levels of cytokeratin 5 regardless of subtype.[11]

Epithelioid mesothelioma is characterized by high levels of calretinin.[11]

Sarcomatous mesothelioma does not express high levels of calretinin.[11]

Other morphological subtypes have been described:

Staging of mesothelioma is based on the recommendation by the International Mesothelioma Interest Group.[53] TNM classification of the primary tumor, lymph node involvement, and distant metastasis is performed. Mesothelioma is staged IaIV (one-A to four) based on the TNM status.[53][54]

Mesothelioma can be prevented in most cases by preventing exposure to asbestos. The US National Institute for Occupational Safety and Health maintains a recommended exposure limit of 0.1 asbestos fiber per cubic centimeter.[24]

There is no universally agreed protocol for screening people who have been exposed to asbestos. Screening tests might diagnose mesothelioma earlier than conventional methods thus improving the survival prospects for patients. The serum osteopontin level might be useful in screening asbestos-exposed people for mesothelioma. The level of soluble mesothelin-related protein is elevated in the serum of about 75% of patients at diagnosis and it has been suggested that it may be useful for screening.[55] Doctors have begun testing the Mesomark assay which measures levels of soluble mesothelin-related proteins (SMRPs) released by mesothelioma cells.[56]

Mesothelioma is generally resistant to radiation and chemotherapy treatment. Long-term survival and cures are exceedingly rare.[11] Treatment of malignant mesothelioma at earlier stages has a better prognosis. Clinical behavior of the malignancy is affected by several factors including the continuous mesothelial surface of the pleural cavity which favors local metastasis via exfoliated cells, invasion to underlying tissue and other organs within the pleural cavity, and the extremely long latency period between asbestos exposure and development of the disease. The histological subtype and the patient's age and health status also help predict prognosis. The epithelioid histology responds better to treatment and has a survival advantage over sarcomatoid histology.[57]

Surgery, by itself, has proved disappointing. In one large series, the median survival with surgery (including extrapleural pneumonectomy) was only 11.7 months.[58] However, research indicates varied success when used in combination with radiation and chemotherapy (Duke, 2008), or with one of the latter. A pleurectomy/decortication is the most common surgery, in which the lining of the chest is removed. Less common is an extrapleural pneumonectomy (EPP), in which the lung, lining of the inside of the chest, the hemi-diaphragm and the pericardium are removed.[citation needed] In localized pericardial mesothelioma, pericardectomy can be curative; when the tumor has metastasized, pericardectomy is a palliative care option. The entire tumor is not often able to be removed.[10]

For patients with localized disease, and who can tolerate a radical surgery, radiation can be given post-operatively as a consolidative treatment. The entire hemithorax is treated with radiation therapy, often given simultaneously with chemotherapy. Delivering radiation and chemotherapy after a radical surgery has led to extended life expectancy in selected patient populations. It can also induce severe side-effects, including fatal pneumonitis.[59] As part of a curative approach to mesothelioma, radiotherapy is commonly applied to the sites of chest drain insertion, in order to prevent growth of the tumor along the track in the chest wall.[citation needed]

Although mesothelioma is generally resistant to curative treatment with radiotherapy alone, palliative treatment regimens are sometimes used to relieve symptoms arising from tumor growth, such as obstruction of a major blood vessel. Radiation therapy, when given alone with curative intent, has never been shown to improve survival from mesothelioma. The necessary radiation dose to treat mesothelioma that has not been surgically removed would be beyond human tolerance.[citation needed] Radiotherapy is of some use in pericardial mesothelioma.[10]

Chemotherapy is the only treatment for mesothelioma that has been proven to improve survival in randomised and controlled trials. The landmark study published in 2003 by Vogelzang and colleagues compared cisplatin chemotherapy alone with a combination of cisplatin and pemetrexed (brand name Alimta) chemotherapy in patients who had not received chemotherapy for malignant pleural mesothelioma previously and were not candidates for more aggressive "curative" surgery.[60] This trial was the first to report a survival advantage from chemotherapy in malignant pleural mesothelioma, showing a statistically significant improvement in median survival from 10 months in the patients treated with cisplatin alone to 13.3 months in the group of patients treated with cisplatin in the combination with pemetrexed and who also received supplementation with folate and vitamin B12. Vitamin supplementation was given to most patients in the trial and pemetrexed related side effects were significantly less in patients receiving pemetrexed when they also received daily oral folate 500mcg and intramuscular vitamin B12 1000mcg every 9 weeks compared with patients receiving pemetrexed without vitamin supplementation. The objective response rate increased from 20% in the cisplatin group to 46% in the combination pemetrexed group. Some side effects such as nausea and vomiting, stomatitis, and diarrhoea were more common in the combination pemetrexed group but only affected a minority of patients and overall the combination of pemetrexed and cisplatin was well tolerated when patients received vitamin supplementation; both quality of life and lung function tests improved in the combination pemetrexed group. In February 2004, the United States Food and Drug Administration approved pemetrexed for treatment of malignant pleural mesothelioma. However, there are still unanswered questions about the optimal use of chemotherapy, including when to start treatment, and the optimal number of cycles to give.[citation needed] Cisplatin and pemetrexed together give patients a median survival of 12.1 months.[11]

Cisplatin in combination with raltitrexed has shown an improvement in survival similar to that reported for pemetrexed in combination with cisplatin, but raltitrexed is no longer commercially available for this indication. For patients unable to tolerate pemetrexed, cisplatin in combination with gemcitabine or vinorelbine is an alternative, or vinorelbine on its own, although a survival benefit has not been shown for these drugs. For patients in whom cisplatin cannot be used, carboplatin can be substituted but non-randomised data have shown lower response rates and high rates of haematological toxicity for carboplatin-based combinations, albeit with similar survival figures to patients receiving cisplatin.[61]

In January 2009, the United States FDA approved using conventional therapies such as surgery in combination with radiation and or chemotherapy on stage I or II Mesothelioma after research conducted by a nationwide study by Duke University concluded an almost 50 point increase in remission rates.[citation needed]

In pericardial mesothelioma, chemotherapy - typically adriamycin and/or cisplatin - is primarily used to shrink the tumor and is not curative.[10]

Treatment regimens involving immunotherapy have yielded variable results. For example, intrapleural inoculation of Bacillus Calmette-Gurin (BCG) in an attempt to boost the immune response, was found to be of no benefit to the patient (while it may benefit patients with bladder cancer). Mesothelioma cells proved susceptible to in vitro lysis by LAK cells following activation by interleukin-2 (IL-2), but patients undergoing this particular therapy experienced major side effects. Indeed, this trial was suspended in view of the unacceptably high levels of IL-2 toxicity and the severity of side effects such as fever and cachexia. Nonetheless, other trials involving interferon alpha have proved more encouraging with 20% of patients experiencing a greater than 50% reduction in tumor mass combined with minimal side effects.[citation needed]

This technique is used in conjunction with surgery,[62] including in patients with malignant pleural mesothelioma.[63] The surgeon removes as much of the tumor as possible followed by the direct administration of a chemotherapy agent, heated to between 40 and 48C, in the abdomen. The fluid is perfused for 60 to 120 minutes and then drained. High concentrations of selected drugs are then administered into the abdominal and pelvic surfaces. Heating the chemotherapy treatment increases the penetration of the drugs into tissues. Also, heating itself damages the malignant cells more than the normal cells.[citation needed]

All of the standard approaches to treating solid tumorsradiation, chemotherapy, and surgeryhave been investigated in patients with malignant pleural mesothelioma. Although surgery, by itself, is not very effective, surgery combined with adjuvant chemotherapy and radiation (trimodality therapy) has produced significant survival extension (314 years) among patients with favorable prognostic factors.[64] However, other large series of examining multimodality treatment have only demonstrated modest improvement in survival (median survival 14.5 months and only 29.6% surviving 2 years).[58] Reducing the bulk of the tumor with cytoreductive surgery is key to extending survival. Two surgeries have been developed: extrapleural pneumonectomy and pleurectomy/decortication. The indications for performing these operations are unique. The choice of operation namely depends on the size of the patient's tumor. This is an important consideration because tumor volume has been identified as a prognostic factor in mesothelioma.[65] Pleurectomy/decortication spares the underlying lung and is performed in patients with early stage disease when the intention is to remove all gross visible tumor (macroscopic complete resection), not simply palliation.[66] Extrapleural pneumonectomy is a more extensive operation that involves resection of the parietal and visceral pleurae, underlying lung, ipsilateral (same side) diaphragm, and ipsilateral pericardium. This operation is indicated for a subset of patients with more advanced tumors, who can tolerate a pneumonectomy.[67]

Mesothelioma often has a poor prognosis. Typical survival despite surgery is between 12 and 21 months depending on the stage of disease at diagnosis with about 7.5% of people surviving for 5 years.[68]

Women, young people, people with low-stage cancers, and people with epithelioid cancers have better prognoses.[11] Negative prognostic factors include sarcomatoid or biphasic histology, high platelet counts (above 400,000), age over 50 years, white blood cell counts above 15.5, low glucose levels in the pleural fluid, low albumin levels, and high fibrinogen levels. Several markers are under investigation as prognostic factors, including nuclear grade, and serum c-reactive protein. Long-term survival is rare.[49]

Pericardial mesothelioma has a 10-month median survival time.[10]

In peritoneal mesothelioma, high expression of WT-1 protein indicates a worse prognosis.[11]

Although reported incidence rates have increased in the past 20 years, mesothelioma is still a relatively rare cancer. The incidence rate varies from one country to another, from a low rate of less than 1 per 1,000,000 in Tunisia and Morocco, to the highest rate in Britain, Australia and Belgium: 30 per 1,000,000 per year.[69] For comparison, populations with high levels of smoking can have a lung cancer incidence of over 1,000 per 1,000,000. Incidence of malignant mesothelioma currently ranges from about 7 to 40 per 1,000,000 in industrialized Western nations, depending on the amount of asbestos exposure of the populations during the past several decades.[70] Worldwide incidence is estimated at 1-6 per 1,000,000.[11] Incidence of mesothelioma lags behind that of asbestosis due to the longer time it takes to develop; due to the cessation of asbestos use in developed countries, mesothelioma incidence is expected to decrease.[24] Incidence is expected to continue increasing in developing countries due to continuing use of asbestos.[11] Mesothelioma occurs more often in men than in women and risk increases with age, but this disease can appear in either men or women at any age. Approximately one fifth to one third of all mesotheliomas are peritoneal.[citation needed] Less than 5% of mesotheliomas are pericardial. The prevalence of pericardial mesothelioma is less than 0.002%; it is more common in men than women. It typically occurs in a person's 50s-70s.[10][71]

Between 1940 and 1979, approximately 27.5 million people were occupationally exposed to asbestos in the United States.[72] Between 1973 and 1984, the incidence of pleural mesothelioma among Caucasian males increased 300%. From 1980 to the late 1990s, the death rate from mesothelioma in the USA increased from 2,000 per year to 3,000, with men four times more likely to acquire it than women.[citation needed] More than 80% of mesotheliomas are caused by asbestos exposure.[11]

The incidence of peritoneal mesothelioma is 0.53.0 per million per year in men, and 0.22.0 per million per year in women.[73]

Mesothelioma accounts for less than 1% of all cancers diagnosed in the UK, (around 2,600 people were diagnosed with the disease in 2011), and it is the seventeenth most common cause of cancer death (around 2,400 people died in 2012).[74]

The connection between asbestos exposure and mesothelioma was discovered in the 1970s. In the United States, asbestos manufacture stopped in 2002. Asbestos exposure thus shifted from workers in asbestos textile mills, friction product manufacturing, cement pipe fabrication, and insulation manufacture and installation to maintenance workers in asbestos-containing buildings.[24]

Mesothelioma, though rare, has had a number of notable patients:

Although life expectancy with this disease is typically limited, there are notable survivors. In July 1982, Stephen Jay Gould, a well-regarded paleontologist, was diagnosed with peritoneal mesothelioma. After his diagnosis, Gould wrote "The Median Isn't the Message",[81] in which he argued that statistics such as median survival are useful abstractions, not destiny. Gould lived for another 20 years, eventually succumbing to cancer not linked to his mesothelioma.

Some people who were exposed to asbestos have collected damages for an asbestos-related disease, including mesothelioma. Compensation via asbestos funds or class action lawsuits is an important issue in law practices regarding mesothelioma.[citation needed]

The first lawsuits against asbestos manufacturers were in 1929. Since then, many lawsuits have been filed against asbestos manufacturers and employers, for neglecting to implement safety measures after the links between asbestos, asbestosis, and mesothelioma became known (some reports seem to place this as early as 1898). The liability resulting from the sheer number of lawsuits and people affected has reached billions of dollars.[82] The amounts and method of allocating compensation have been the source of many court cases, reaching up to the United States Supreme Court, and government attempts at resolution of existing and future cases. However, to date, the US Congress has not stepped in and there are no federal laws governing asbestos compensation.[83]In 2013, the "Furthering Asbestos Claim Transparency (FACT) Act of 2013" passed the US House of representatives and was sent to the US Senate, where it was referred to the Senate Judiciary Committee.[84] As the Senate did not vote on it before the end of the 113th Congress, it died in committee. It was revived in the 114th Congress, where it has not yet been brought before the House for a vote.[85]

The first lawsuit against asbestos manufacturers was brought in 1929. The parties settled that lawsuit, and as part of the agreement, the attorneys agreed not to pursue further cases. In 1960, an article published by Wagner et al. was seminal in establishing mesothelioma as a disease arising from exposure to asbestos.[86] The article referred to over 30 case studies of people who had suffered from mesothelioma in South Africa. Some exposures were transient and some were mine workers. Before the use of advanced microscopy techniques, malignant mesothelioma was often diagnosed as a variant form of lung cancer.[87] In 1962, McNulty reported the first diagnosed case of malignant mesothelioma in an Australian asbestos worker.[88] The worker had worked in the mill at the asbestos mine in Wittenoom from 1948 to 1950.[citation needed]

In the town of Wittenoom, asbestos-containing mine waste was used to cover schoolyards and playgrounds. In 1965, an article in the British Journal of Industrial Medicine established that people who lived in the neighbourhoods of asbestos factories and mines, but did not work in them, had contracted mesothelioma.[citation needed]

Despite proof that the dust associated with asbestos mining and milling causes asbestos-related disease, mining began at Wittenoom in 1943 and continued until 1966. In 1974, the first public warnings of the dangers of blue asbestos were published in a cover story called "Is this Killer in Your Home?" in Australia's Bulletin magazine. In 1978, the Western Australian Government decided to phase out the town of Wittenoom, following the publication of a Health Dept. booklet, "The Health Hazard at Wittenoom", containing the results of air sampling and an appraisal of worldwide medical information.[citation needed]

By 1979, the first writs for negligence related to Wittenoom were issued against CSR and its subsidiary ABA, and the Asbestos Diseases Society was formed to represent the Wittenoom victims.[citation needed]

In Leeds, England the Armley asbestos disaster involved several court cases against Turner & Newall where local residents who contracted mesothelioma demanded compensation because of the asbestos pollution from the company's factory. One notable case was that of June Hancock, who contracted the disease in 1993 and died in 1997.[89]

The WT-1 protein is overexpressed in mesothelioma and is being researched as a potential target for drugs.[11]

There are two high-confidence miRNAs that can potentially serve as biomarkers of asbestos exposure and malignant mesothelioma. Validation studies are needed to assess their relevance.[90]

Mesothelioma at Curlie

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Mesothelioma - Wikipedia

Mesothelioma – Symptoms and causes – Mayo Clinic

Overview

Malignant mesothelioma (me-zoe-thee-lee-O-muh) is a type of cancer that occurs in the thin layer of tissue that covers the majority of your internal organs (mesothelium).

Mesothelioma is an aggressive and deadly form of cancer. Mesothelioma treatments are available, but for many people with mesothelioma, a cure isn't possible.

Doctors divide mesothelioma into different types based on what part of the mesothelium is affected. Mesothelioma most often affects the tissue that surrounds the lungs (pleura). This type is called pleural mesothelioma. Other, rarer types of mesothelioma affect tissue in the abdomen (peritoneal mesothelioma), around the heart and around the testicles.

Mesothelioma care at Mayo Clinic

Signs and symptoms of mesothelioma vary depending on where the cancer occurs.

Pleural mesothelioma, which affects the tissue that surrounds the lungs, causes signs and symptoms that may include:

Peritoneal mesothelioma, which occurs in tissue in the abdomen, causes signs and symptoms that may include:

Signs and symptoms of other types of mesothelioma are unclear, since these forms of the disease are very rare.

Pericardial mesothelioma, which affects tissue that surrounds the heart, can cause signs and symptoms such as breathing difficulty and chest pains.

Mesothelioma of tunica vaginalis, which affects tissue surrounding the testicles, may be first detected as swelling or a mass on a testicle.

See your doctor if you have signs and symptoms that worry you. Signs and symptoms of mesothelioma aren't specific to this disease and, due to the rarity of mesothelioma, are more likely to be related to other conditions. If any persistent signs and symptoms seem unusual or bothersome, ask your doctor to evaluate them. Tell your doctor if you've been exposed to asbestos.

In general, cancer begins when a series of changes (mutations) happens in a cell's DNA. The DNA contains the instructions that tell a cell what to do. The mutations tell the cell to grow and multiply out of control. The abnormal cells accumulate and form a tumor.

It isn't clear what causes the initial genetic mutations that lead to mesothelioma, though researchers have identified factors that may increase the risk. It's likely that cancers form because of an interaction between many factors, such as inherited conditions, your environment, your health conditions and your lifestyle choices.

Most mesotheliomas are thought to be related to asbestos exposure. Asbestos is a mineral that's found naturally in the environment. Asbestos fibers are strong and resistant to heat, making them useful in a wide variety of applications, such as in insulation, brakes, shingles, flooring and many other products.

When asbestos is broken up, such as during the mining process or when removing asbestos insulation, dust may be created. If the dust is inhaled or swallowed, the asbestos fibers will settle in the lungs or in the stomach, where they can cause irritation that may lead to mesothelioma. Exactly how this happens isn't understood. It can take 20 to 60 years or more for mesothelioma to develop after asbestos exposure.

Most people with asbestos exposure never develop mesothelioma. This indicates that other factors may be involved in determining whether someone gets mesothelioma. For instance, you could inherit a predisposition to cancer or some other condition could increase your risk.

Factors that may increase the risk of mesothelioma include:

As pleural mesothelioma spreads in the chest, it puts pressure on the structures in that area. This can cause complications, such as:

Reducing your exposure to asbestos may lower your risk of mesothelioma.

Most people with mesothelioma were exposed to the asbestos fibers at work. Workers who may encounter asbestos fibers include:

Ask your employer whether you have a risk of asbestos exposure on the job.

Follow all safety precautions in your workplace, such as wearing protective equipment. You may also be required to shower and change out of your work clothes before taking a lunch break or going home. Talk to your doctor about other precautions you can take to protect yourself from asbestos exposure.

Older homes and buildings may contain asbestos. In many cases, it's more dangerous to remove the asbestos than it is to leave it intact. Breaking up asbestos may cause fibers to become airborne, where they can be inhaled. Consult experts trained to detect asbestos in your home. These experts may test the air in your home to determine whether the asbestos is a risk to your health. Don't attempt to remove asbestos from your home hire a qualified expert.

Jan. 15, 2019

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Mesothelioma - Symptoms and causes - Mayo Clinic

Mesothelioma | Symptoms, Causes, and Prognosis Explained

Asbestos exposure can be blamed for causing nearly all of the approximately 3,000 cases of mesothelioma diagnosed every year. Most of that exposure occurred in the workplace.

Employees exposed and put at risk of asbestos-related diseases never knew about the dangers until it was too late. While not all workers exposed to asbestos later got sick, many ended up with life-threatening conditions.

Many companies used asbestos heavily until the government began regulating it in the 1970s. Workers who were more likely to be exposed include industrial workers, sailors and shipyard workers, construction laborers and skilled tradesmen, and miners, among many others.

Exposure to asbestos is now declining and occurs much less often than it did in the past. But not all the damage has yet been seen. People are still getting diagnosed with mesothelioma now because of the cancer's long latency period. Decades can pass between exposure and symptoms that lead to a diagnosis.

Researchers have made great improvements in diagnosing and treating mesothelioma. They are helping people live longer, but mesothelioma is still an aggressive and deadly type of cancer. There is no cure for mesothelioma and remission is extremely rare.

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Mesothelioma | Symptoms, Causes, and Prognosis Explained

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Mesothelioma – Wikipedia

Cancer associated with asbestos

Mesothelioma is a type of cancer that develops from the thin layer of tissue that covers many of the internal organs (known as the mesothelium).[9] The most common area affected is the lining of the lungs and chest wall.[1][3] Less commonly the lining of the abdomen and rarely the sac surrounding the heart,[10] or the sac surrounding the testis may be affected.[1][11] Signs and symptoms of mesothelioma may include shortness of breath due to fluid around the lung, a swollen abdomen, chest wall pain, cough, feeling tired, and weight loss.[1] These symptoms typically come on slowly.[2]

More than 80% of mesothelioma cases are caused by exposure to asbestos.[3] The greater the exposure the greater the risk.[3] As of 2013, about 125 million people worldwide have been exposed to asbestos at work.[12] High rates of disease occur in people who mine asbestos, produce products from asbestos, work with asbestos products, live with asbestos workers, or work in buildings containing asbestos.[3] Asbestos exposure and the onset of cancer are generally separated by about 40 years.[3] Washing the clothing of someone who worked with asbestos also increases the risk.[12] Other risk factors include genetics and infection with the simian virus 40.[3] The diagnosis may be suspected based on chest X-ray and CT scan findings, and is confirmed by either examining fluid produced by the cancer or by a tissue biopsy of the cancer.[2]

Prevention centers around reducing exposure to asbestos.[4] Treatment often includes surgery, radiation therapy, and chemotherapy.[5] A procedure known as pleurodesis, which involves using substances such as talc to scar together the pleura, may be used to prevent more fluid from building up around the lungs.[5] Chemotherapy often includes the medications cisplatin and pemetrexed.[2] The percentage of people that survive five years following diagnosis is on average 8% in the United States.[6]

In 2015, about 60,800 people had mesothelioma, and 32,000 died from the disease.[7][8] Rates of mesothelioma vary in different areas of the world.[3] Rates are higher in Australia, the United Kingdom, and lower in Japan.[3] It occurs in about 3,000 people per year in the United States.[13] It occurs more often in males than females.[3] Rates of disease have increased since the 1950s.[3] Diagnosis typically occurs after the age of 65 and most deaths occur around 70 years old.[3] The disease was rare before the commercial use of asbestos.[3]

Symptoms or signs of mesothelioma may not appear until 20 to 50 years (or more) after exposure to asbestos. Shortness of breath, cough, and pain in the chest due to an accumulation of fluid in the pleural space (pleural effusion) are often symptoms of pleural mesothelioma.[14]

Mesothelioma that affects the pleura can cause these signs and symptoms:[14]

In severe cases, the person may have many tumor masses. The individual may develop a pneumothorax, or collapse of the lung. The disease may metastasize, or spread to other parts of the body.

The most common symptoms of peritoneal mesothelioma are abdominal swelling and pain due to ascites (a buildup of fluid in the abdominal cavity). Other features may include weight loss, fever, night sweats, poor appetite, vomiting, constipation, and umbilical hernia.[15] If the cancer has spread beyond the mesothelium to other parts of the body, symptoms may include pain, trouble swallowing, or swelling of the neck or face.[citation needed]These symptoms may be caused by mesothelioma or by other, less serious conditions.

Tumors that affect the abdominal cavity often do not cause symptoms until they are at a late stage. Symptoms include:[citation needed]

Pericardial mesothelioma is not well characterized, but observed cases have included cardiac symptoms, specifically constrictive pericarditis, heart failure, pulmonary embolism, and cardiac tamponade. They have also included nonspecific symptoms, including substernal chest pain, orthopnea (shortness of breath when lying flat), and cough. These symptoms are caused by the tumor encasing or infiltrating the heart.[10]

In severe cases of the disease, the following signs and symptoms may be present:[citation needed]

If a mesothelioma forms metastases, these most commonly involve the liver, adrenal gland, kidney, or other lung.[16]

Working with asbestos is the most common risk factor for mesothelioma.[17] However, mesothelioma has been reported in some individuals without any known exposure to asbestos. Tentative evidence also raises concern about carbon-fibre nanotubes.[18][19]

The incidence of mesothelioma has been found to be higher in populations living near naturally occurring asbestos. People can be exposed to naturally occurring asbestos in areas where mining or road construction is occurring, or when the asbestos-containing rock is naturally weathered. Another common route of exposure is through asbestos-containing soil, which is used to whitewash, plaster, and roof houses in Greece.[12] In central Cappadocia, Turkey, mesothelioma was causing 50% of all deaths in three small villagesTuzky, Karain, and Sarhdr. Initially, this was attributed to erionite. Environmental exposure to asbestos has caused mesothelioma in places other than Turkey, including Corsica, Greece, Cyprus, China, and California.[12][20][21] In the northern Greek mountain town of Metsovo, this exposure had resulted in mesothelioma incidence around 300 times more than expected in asbestos-free populations, and was associated with very frequent pleural calcification known as "Metsovo Lung".[22][23]

The documented presence of asbestos fibers in water supplies and food products has fostered concerns about the possible impact of long-term and, as yet, unknown exposure of the general population to these fibers.[citation needed]

Exposure to talc is also a risk factor for mesothelioma; exposure can affect those who live near talc mines, work in talc mines, or work in talc mills.[24]

In the United States, asbestos is considered the major cause of malignant mesothelioma[25] and has been considered "indisputably"[26] associated with the development of mesothelioma. Indeed, the relationship between asbestos and mesothelioma is so strong that many consider mesothelioma a signal or sentinel tumor.[27][28][29][30] A history of asbestos exposure exists in most cases.

Pericardial mesothelioma may not be associated with asbestos exposure.[10]

Asbestos was known in antiquity, but it was not mined and widely used commercially until the late 19th century. Its use greatly increased during World War II. Since the early 1940s, millions of American workers have been exposed to asbestos dust. Initially, the risks associated with asbestos exposure were not publicly known. However, an increased risk of developing mesothelioma was later found among naval personnel (e.g., Navy, Marine Corps, and Coast Guard), shipyard workers, people who work in asbestos mines and mills, producers of asbestos products, workers in the heating and construction industries, and other tradespeople. Today, the official position of the U.S. Occupational Safety and Health Administration (OSHA) and the U.S. EPA is that protections and "permissible exposure limits" required by U.S. regulations, while adequate to prevent most asbestos-related non-malignant disease, are not adequate to prevent or protect against asbestos-related cancers such as mesothelioma.[31] Likewise, the British Government's Health and Safety Executive (HSE) states formally that any threshold for exposure to asbestos must be at a very low level and it is widely agreed that if any such threshold does exist at all, then it cannot currently be quantified. For practical purposes, therefore, HSE assumes that no such "safe" threshold exists. Others have noted as well that there is no evidence of a threshold level below which there is no risk of mesothelioma.[32] There appears to be a linear, doseresponse relationship, with increasing dose producing increasing risk of disease.[33] Nevertheless, mesothelioma may be related to brief, low level or indirect exposures to asbestos.[26] The dose necessary for effect appears to be lower for asbestos-induced mesothelioma than for pulmonary asbestosis or lung cancer.[26] Again, there is no known safe level of exposure to asbestos as it relates to increased risk of mesothelioma.

The time from first exposure to onset of the disease, is between 25 and 70 years.[34] It is virtually never less than fifteen years and peaks at 3040 years.[26][35] The duration of exposure to asbestos causing mesothelioma can be short. For example, cases of mesothelioma have been documented with only 13 months of exposure.[36][37]

Exposure to asbestos fibers has been recognized as an occupational health hazard since the early 20th century. Numerous epidemiological studies have associated occupational exposure to asbestos with the development of pleural plaques, diffuse pleural thickening, asbestosis, carcinoma of the lung and larynx, gastrointestinal tumors, and diffuse malignant mesothelioma of the pleura and peritoneum. Asbestos has been widely used in many industrial products, including cement, brake linings, gaskets, roof shingles, flooring products, textiles, and insulation.[38]

Commercial asbestos mining at Wittenoom, Western Australia, took place from 1937 to 1966. The first case of mesothelioma in the town occurred in 1960. The second case was in 1969, and new cases began to appear more frequently thereafter. The lag time between initial exposure to asbestos and the development of mesothelioma varied from 12 years 9 months up to 58 years.[39] A cohort study of miners employed at the mine reported that 85 deaths attributable to mesothelioma had occurred by 1985. By 1994, 539 reported deaths due to mesothelioma had been reported in Western Australia.[citation needed]

Occupational exposure to asbestos in the United States mainly occurs when people are maintaining buildings that already have asbestos. Approximately 1.3 million US workers are exposed to asbestos annually; in 2002, an estimated 44,000 miners were potentially exposed to asbestos.[24]

Family members and others living with asbestos workers have an increased risk of developing mesothelioma, and possibly other asbestos-related diseases.[11][40][41] This risk may be the result of exposure to asbestos dust brought home on the clothing and hair of asbestos workers via washing a worker's clothes or coming into contact with asbestos-contaminated work clothing.[12][24] To reduce the chance of exposing family members to asbestos fibres, asbestos workers are usually required to shower and change their clothing before leaving the workplace.[citation needed]

Many building materials used in both public and domestic premises prior to the banning of asbestos may contain asbestos. Those performing renovation works or DIY activities may expose themselves to asbestos dust. In the UK, use of chrysotile asbestos was banned at the end of 1999. Brown and blue asbestos were banned in the UK around 1985. Buildings built or renovated prior to these dates may contain asbestos materials.[citation needed]

In a recent research carried on white American population in 2012, it was found that people with a germline mutation in their BAP1 gene are at higher risk of developing mesothelioma and uveal melanoma.[42]

Erionite is a zeolite mineral with similar properties to asbestos and is known to cause mesothelioma.[11] Detailed epidemiological investigation has shown that erionite causes mesothelioma mostly in families with a genetic predisposition.[12][20][21] Erionite is found in deposits in the Western United States, where it is used in gravel for road surfacing, and in Turkey, where it is used to construct homes. In Turkey, the United States, and Mexico, erionite has been associated with mesothelioma and has thus been designated a "known human carcinogen" by the US National Toxicology Program.[21]

In rare cases, mesothelioma has also been associated with irradiation of the chest or abdomen, intrapleural thorium dioxide (thorotrast) as a contrast medium, and inhalation of other fibrous silicates, such as erionite or talc.[11][24] Some studies suggest that simian virus 40 (SV40) may act as a cofactor in the development of mesothelioma.[24] This has been confirmed in animal studies,[43][44] but studies in humans are inconclusive.[43][45][46]

The mesothelium consists of a single layer of flattened to cuboidal cells forming the epithelial lining of the serous cavities of the body including the peritoneal, pericardial and pleural cavities. Deposition of asbestos fibers in the parenchyma of the lung may result in the penetration of the visceral pleura from where the fiber can then be carried to the pleural surface, thus leading to the development of malignant mesothelial plaques. The processes leading to the development of peritoneal mesothelioma remain unresolved, although it has been proposed that asbestos fibers from the lung are transported to the abdomen and associated organs via the lymphatic system. Additionally, asbestos fibers may be deposited in the gut after ingestion of sputum contaminated with asbestos fibers.[citation needed]

Pleural contamination with asbestos or other mineral fibers has been shown to cause cancer. Long thin asbestos fibers (blue asbestos, amphibole fibers) are more potent carcinogens than "feathery fibers" (chrysotile or white asbestos fibers).[26] However, there is now evidence that smaller particles may be more dangerous than the larger fibers. They remain suspended in the air where they can be inhaled, and may penetrate more easily and deeper into the lungs. "We probably will find out a lot more about the health aspects of asbestos from [the World Trade Center attack], unfortunately," said Dr. Alan Fein, chief of pulmonary and critical-care medicine at North Shore-Long Island Jewish Health System.[47]

Mesothelioma development in rats has been demonstrated following intra-pleural inoculation of phosphorylated chrysotile fibers. It has been suggested that in humans, transport of fibers to the pleura is critical to the pathogenesis of mesothelioma. This is supported by the observed recruitment of significant numbers of macrophages and other cells of the immune system to localized lesions of accumulated asbestos fibers in the pleural and peritoneal cavities of rats. These lesions continued to attract and accumulate macrophages as the disease progressed, and cellular changes within the lesion culminated in a morphologically malignant tumor.[citation needed]

Experimental evidence suggests that asbestos acts as a complete carcinogen with the development of mesothelioma occurring in sequential stages of initiation and promotion. The molecular mechanisms underlying the malignant transformation of normal mesothelial cells by asbestos fibers remain unclear despite the demonstration of its oncogenic capabilities (see next-but-one paragraph). However, complete in vitro transformation of normal human mesothelial cells to a malignant phenotype following exposure to asbestos fibers has not yet been achieved. In general, asbestos fibers are thought to act through direct physical interactions with the cells of the mesothelium in conjunction with indirect effects following interaction with inflammatory cells such as macrophages.[citation needed]

Analysis of the interactions between asbestos fibers and DNA has shown that phagocytosed fibers are able to make contact with chromosomes, often adhering to the chromatin fibers or becoming entangled within the chromosome. This contact between the asbestos fiber and the chromosomes or structural proteins of the spindle apparatus can induce complex abnormalities. The most common abnormality is monosomy of chromosome 22. Other frequent abnormalities include structural rearrangement of 1p, 3p, 9p and 6q chromosome arms.[citation needed]

Common gene abnormalities in mesothelioma cell lines include deletion of the tumor suppressor genes:[citation needed]

Asbestos has also been shown to mediate the entry of foreign DNA into target cells. Incorporation of this foreign DNA may lead to mutations and oncogenesis by several possible mechanisms:

Several genes are commonly mutated in mesothelioma, and may be prognostic factors. These include epidermal growth factor receptor (EGFR) and C-Met, receptor tyrosine kinases which are overexpressed in many mesotheliomas. Some association has been found with EGFR and epithelioid histology but no clear association has been found between EGFR overexpression and overall survival. Expression of AXL receptor tyrosine kinase is a negative prognostic factor. Expression of PDGFRB is a positive prognostic factor.[49] In general, mesothelioma is characterized by loss of function in tumor suppressor genes, rather than by an overexpression or gain of function in oncogenes.[50]

As an environmentally triggered malignancy, mesothelioma tumors have been found to be polyclonal in origin, by performing a X-inactivation based assay on epitheloid and biphasic tumors obtained from female patients.[51] These results suggest that an environmental factor, most likely asbestos exposure, may damage and transform a group of cells in the tissue, resulting in a population of tumor cells that are, albeit only slightly, genetically different.[52]

Asbestos fibers have been shown to alter the function and secretory properties of macrophages, ultimately creating conditions which favour the development of mesothelioma. Following asbestos phagocytosis, macrophages generate increased amounts of hydroxyl radicals, which are normal by-products of cellular anaerobic metabolism. However, these free radicals are also known clastogenic (chromosome-breaking) and membrane-active agents thought to promote asbestos carcinogenicity. These oxidants can participate in the oncogenic process by directly and indirectly interacting with DNA, modifying membrane-associated cellular events, including oncogene activation and perturbation of cellular antioxidant defences.[citation needed]

Asbestos also may possess immunosuppressive properties. For example, chrysotile fibres have been shown to depress the in vitro proliferation of phytohemagglutinin-stimulated peripheral blood lymphocytes, suppress natural killer cell lysis and significantly reduce lymphokine-activated killer cell viability and recovery. Furthermore, genetic alterations in asbestos-activated macrophages may result in the release of potent mesothelial cell mitogens such as platelet-derived growth factor (PDGF) and transforming growth factor- (TGF-) which in turn, may induce the chronic stimulation and proliferation of mesothelial cells after injury by asbestos fibres.[citation needed]

Diagnosis of mesothelioma can be suspected with imaging but is confirmed with biopsy. It must be clinically and histologically differentiated from other pleural and pulmonary malignancies, including reactive pleural disease, primary lung carcinoma, pleural metastases of other cancers, and other primary pleural cancers.[11]Primary pericardial mesothelioma is often diagnosed after it has metastasized to lymph nodes or the lungs.[10]

Diagnosing mesothelioma is often difficult because the symptoms are similar to those of a number of other conditions. Diagnosis begins with a review of the patient's medical history. A history of exposure to asbestos may increase clinical suspicion for mesothelioma. A physical examination is performed, followed by chest X-ray and often lung function tests. The X-ray may reveal pleural thickening commonly seen after asbestos exposure and increases suspicion of mesothelioma.[14] A CT (or CAT) scan or an MRI is usually performed. If a large amount of fluid is present, abnormal cells may be detected by cytopathology if this fluid is aspirated with a syringe.[10] For pleural fluid, this is done by thoracentesis or tube thoracostomy (chest tube); for ascites, with paracentesis or ascitic drain; and for pericardial effusion with pericardiocentesis. While absence of malignant cells on cytology does not completely exclude mesothelioma, it makes it much more unlikely, especially if an alternative diagnosis can be made (e.g., tuberculosis, heart failure).[citation needed] However, with primary pericardial mesothelioma, pericardial fluid may not contain malignant cells and a tissue biopsy is more useful in diagnosis.[10] Using conventional cytology diagnosis of malignant mesothelioma is difficult, but immunohistochemistry has greatly enhanced the accuracy of cytology.[citation needed]

Generally, a biopsy is needed to confirm a diagnosis of malignant mesothelioma. A doctor removes a sample of tissue for examination under a microscope by a pathologist. A biopsy may be done in different ways, depending on where the abnormal area is located. If the cancer is in the chest, the doctor may perform a thoracoscopy. In this procedure, the doctor makes a small cut through the chest wall and puts a thin, lighted tube called a thoracoscope into the chest between two ribs. Thoracoscopy allows the doctor to look inside the chest and obtain tissue samples. Alternatively, the chest surgeon might directly open the chest (thoracotomy). If the cancer is in the abdomen, the doctor may perform a laparoscopy. To obtain tissue for examination, the doctor makes a small incision in the abdomen and inserts a special instrument into the abdominal cavity. If these procedures do not yield enough tissue, an open surgical procedure may be necessary.[citation needed]

Immunohistochemical studies play an important role for the pathologist in differentiating malignant mesothelioma from neoplastic mimics, such as breast or lung cancer that has metastasized to the pleura. There are numerous tests and panels available, but no single test is perfect for distinguishing mesothelioma from carcinoma or even benign versus malignant. The positive markers indicate that mesothelioma is present; if other markers are positive it may indicate another type of cancer, such as breast or lung adenocarcinoma. Calretinin is a particularly important marker in distinguishing mesothelioma from metastatic breast or lung cancer.[11]

There are three main histological subtypes of malignant mesothelioma: epithelioid, sarcomatous, and biphasic. Epithelioid and biphasic mesothelioma make up approximately 75-95% of mesotheliomas and have been well characterized histologically, whereas sarcomatous mesothelioma has not been studied extensively. Most mesotheliomas express high levels of cytokeratin 5 regardless of subtype.[11]

Epithelioid mesothelioma is characterized by high levels of calretinin.[11]

Sarcomatous mesothelioma does not express high levels of calretinin.[11]

Other morphological subtypes have been described:

Staging of mesothelioma is based on the recommendation by the International Mesothelioma Interest Group.[53] TNM classification of the primary tumor, lymph node involvement, and distant metastasis is performed. Mesothelioma is staged IaIV (one-A to four) based on the TNM status.[53][54]

Mesothelioma can be prevented in most cases by preventing exposure to asbestos. The US National Institute for Occupational Safety and Health maintains a recommended exposure limit of 0.1 asbestos fiber per cubic centimeter.[24]

There is no universally agreed protocol for screening people who have been exposed to asbestos. Screening tests might diagnose mesothelioma earlier than conventional methods thus improving the survival prospects for patients. The serum osteopontin level might be useful in screening asbestos-exposed people for mesothelioma. The level of soluble mesothelin-related protein is elevated in the serum of about 75% of patients at diagnosis and it has been suggested that it may be useful for screening.[55] Doctors have begun testing the Mesomark assay which measures levels of soluble mesothelin-related proteins (SMRPs) released by mesothelioma cells.[56]

Mesothelioma is generally resistant to radiation and chemotherapy treatment. Long-term survival and cures are exceedingly rare.[11] Treatment of malignant mesothelioma at earlier stages has a better prognosis. Clinical behavior of the malignancy is affected by several factors including the continuous mesothelial surface of the pleural cavity which favors local metastasis via exfoliated cells, invasion to underlying tissue and other organs within the pleural cavity, and the extremely long latency period between asbestos exposure and development of the disease. The histological subtype and the patient's age and health status also help predict prognosis. The epithelioid histology responds better to treatment and has a survival advantage over sarcomatoid histology.[57]

Surgery, by itself, has proved disappointing. In one large series, the median survival with surgery (including extrapleural pneumonectomy) was only 11.7 months.[58] However, research indicates varied success when used in combination with radiation and chemotherapy (Duke, 2008), or with one of the latter. A pleurectomy/decortication is the most common surgery, in which the lining of the chest is removed. Less common is an extrapleural pneumonectomy (EPP), in which the lung, lining of the inside of the chest, the hemi-diaphragm and the pericardium are removed.[citation needed] In localized pericardial mesothelioma, pericardectomy can be curative; when the tumor has metastasized, pericardectomy is a palliative care option. The entire tumor is not often able to be removed.[10]

For patients with localized disease, and who can tolerate a radical surgery, radiation can be given post-operatively as a consolidative treatment. The entire hemithorax is treated with radiation therapy, often given simultaneously with chemotherapy. Delivering radiation and chemotherapy after a radical surgery has led to extended life expectancy in selected patient populations. It can also induce severe side-effects, including fatal pneumonitis.[59] As part of a curative approach to mesothelioma, radiotherapy is commonly applied to the sites of chest drain insertion, in order to prevent growth of the tumor along the track in the chest wall.[citation needed]

Although mesothelioma is generally resistant to curative treatment with radiotherapy alone, palliative treatment regimens are sometimes used to relieve symptoms arising from tumor growth, such as obstruction of a major blood vessel. Radiation therapy, when given alone with curative intent, has never been shown to improve survival from mesothelioma. The necessary radiation dose to treat mesothelioma that has not been surgically removed would be beyond human tolerance.[citation needed] Radiotherapy is of some use in pericardial mesothelioma.[10]

Chemotherapy is the only treatment for mesothelioma that has been proven to improve survival in randomised and controlled trials. The landmark study published in 2003 by Vogelzang and colleagues compared cisplatin chemotherapy alone with a combination of cisplatin and pemetrexed (brand name Alimta) chemotherapy in patients who had not received chemotherapy for malignant pleural mesothelioma previously and were not candidates for more aggressive "curative" surgery.[60] This trial was the first to report a survival advantage from chemotherapy in malignant pleural mesothelioma, showing a statistically significant improvement in median survival from 10 months in the patients treated with cisplatin alone to 13.3 months in the group of patients treated with cisplatin in the combination with pemetrexed and who also received supplementation with folate and vitamin B12. Vitamin supplementation was given to most patients in the trial and pemetrexed related side effects were significantly less in patients receiving pemetrexed when they also received daily oral folate 500mcg and intramuscular vitamin B12 1000mcg every 9 weeks compared with patients receiving pemetrexed without vitamin supplementation. The objective response rate increased from 20% in the cisplatin group to 46% in the combination pemetrexed group. Some side effects such as nausea and vomiting, stomatitis, and diarrhoea were more common in the combination pemetrexed group but only affected a minority of patients and overall the combination of pemetrexed and cisplatin was well tolerated when patients received vitamin supplementation; both quality of life and lung function tests improved in the combination pemetrexed group. In February 2004, the United States Food and Drug Administration approved pemetrexed for treatment of malignant pleural mesothelioma. However, there are still unanswered questions about the optimal use of chemotherapy, including when to start treatment, and the optimal number of cycles to give.[citation needed] Cisplatin and pemetrexed together give patients a median survival of 12.1 months.[11]

Cisplatin in combination with raltitrexed has shown an improvement in survival similar to that reported for pemetrexed in combination with cisplatin, but raltitrexed is no longer commercially available for this indication. For patients unable to tolerate pemetrexed, cisplatin in combination with gemcitabine or vinorelbine is an alternative, or vinorelbine on its own, although a survival benefit has not been shown for these drugs. For patients in whom cisplatin cannot be used, carboplatin can be substituted but non-randomised data have shown lower response rates and high rates of haematological toxicity for carboplatin-based combinations, albeit with similar survival figures to patients receiving cisplatin.[61]

In January 2009, the United States FDA approved using conventional therapies such as surgery in combination with radiation and or chemotherapy on stage I or II Mesothelioma after research conducted by a nationwide study by Duke University concluded an almost 50 point increase in remission rates.[citation needed]

In pericardial mesothelioma, chemotherapy - typically adriamycin and/or cisplatin - is primarily used to shrink the tumor and is not curative.[10]

Treatment regimens involving immunotherapy have yielded variable results. For example, intrapleural inoculation of Bacillus Calmette-Gurin (BCG) in an attempt to boost the immune response, was found to be of no benefit to the patient (while it may benefit patients with bladder cancer). Mesothelioma cells proved susceptible to in vitro lysis by LAK cells following activation by interleukin-2 (IL-2), but patients undergoing this particular therapy experienced major side effects. Indeed, this trial was suspended in view of the unacceptably high levels of IL-2 toxicity and the severity of side effects such as fever and cachexia. Nonetheless, other trials involving interferon alpha have proved more encouraging with 20% of patients experiencing a greater than 50% reduction in tumor mass combined with minimal side effects.[citation needed]

This technique is used in conjunction with surgery,[62] including in patients with malignant pleural mesothelioma.[63] The surgeon removes as much of the tumor as possible followed by the direct administration of a chemotherapy agent, heated to between 40 and 48C, in the abdomen. The fluid is perfused for 60 to 120 minutes and then drained. High concentrations of selected drugs are then administered into the abdominal and pelvic surfaces. Heating the chemotherapy treatment increases the penetration of the drugs into tissues. Also, heating itself damages the malignant cells more than the normal cells.[citation needed]

All of the standard approaches to treating solid tumorsradiation, chemotherapy, and surgeryhave been investigated in patients with malignant pleural mesothelioma. Although surgery, by itself, is not very effective, surgery combined with adjuvant chemotherapy and radiation (trimodality therapy) has produced significant survival extension (314 years) among patients with favorable prognostic factors.[64] However, other large series of examining multimodality treatment have only demonstrated modest improvement in survival (median survival 14.5 months and only 29.6% surviving 2 years).[58] Reducing the bulk of the tumor with cytoreductive surgery is key to extending survival. Two surgeries have been developed: extrapleural pneumonectomy and pleurectomy/decortication. The indications for performing these operations are unique. The choice of operation namely depends on the size of the patient's tumor. This is an important consideration because tumor volume has been identified as a prognostic factor in mesothelioma.[65] Pleurectomy/decortication spares the underlying lung and is performed in patients with early stage disease when the intention is to remove all gross visible tumor (macroscopic complete resection), not simply palliation.[66] Extrapleural pneumonectomy is a more extensive operation that involves resection of the parietal and visceral pleurae, underlying lung, ipsilateral (same side) diaphragm, and ipsilateral pericardium. This operation is indicated for a subset of patients with more advanced tumors, who can tolerate a pneumonectomy.[67]

Mesothelioma often has a poor prognosis. Typical survival despite surgery is between 12 and 21 months depending on the stage of disease at diagnosis with about 7.5% of people surviving for 5 years.[68]

Women, young people, people with low-stage cancers, and people with epithelioid cancers have better prognoses.[11] Negative prognostic factors include sarcomatoid or biphasic histology, high platelet counts (above 400,000), age over 50 years, white blood cell counts above 15.5, low glucose levels in the pleural fluid, low albumin levels, and high fibrinogen levels. Several markers are under investigation as prognostic factors, including nuclear grade, and serum c-reactive protein. Long-term survival is rare.[49]

Pericardial mesothelioma has a 10-month median survival time.[10]

In peritoneal mesothelioma, high expression of WT-1 protein indicates a worse prognosis.[11]

Although reported incidence rates have increased in the past 20 years, mesothelioma is still a relatively rare cancer. The incidence rate varies from one country to another, from a low rate of less than 1 per 1,000,000 in Tunisia and Morocco, to the highest rate in Britain, Australia and Belgium: 30 per 1,000,000 per year.[69] For comparison, populations with high levels of smoking can have a lung cancer incidence of over 1,000 per 1,000,000. Incidence of malignant mesothelioma currently ranges from about 7 to 40 per 1,000,000 in industrialized Western nations, depending on the amount of asbestos exposure of the populations during the past several decades.[70] Worldwide incidence is estimated at 1-6 per 1,000,000.[11] Incidence of mesothelioma lags behind that of asbestosis due to the longer time it takes to develop; due to the cessation of asbestos use in developed countries, mesothelioma incidence is expected to decrease.[24] Incidence is expected to continue increasing in developing countries due to continuing use of asbestos.[11] Mesothelioma occurs more often in men than in women and risk increases with age, but this disease can appear in either men or women at any age. Approximately one fifth to one third of all mesotheliomas are peritoneal.[citation needed] Less than 5% of mesotheliomas are pericardial. The prevalence of pericardial mesothelioma is less than 0.002%; it is more common in men than women. It typically occurs in a person's 50s-70s.[10][71]

Between 1940 and 1979, approximately 27.5 million people were occupationally exposed to asbestos in the United States.[72] Between 1973 and 1984, the incidence of pleural mesothelioma among Caucasian males increased 300%. From 1980 to the late 1990s, the death rate from mesothelioma in the USA increased from 2,000 per year to 3,000, with men four times more likely to acquire it than women.[citation needed] More than 80% of mesotheliomas are caused by asbestos exposure.[11]

The incidence of peritoneal mesothelioma is 0.53.0 per million per year in men, and 0.22.0 per million per year in women.[73]

Mesothelioma accounts for less than 1% of all cancers diagnosed in the UK, (around 2,600 people were diagnosed with the disease in 2011), and it is the seventeenth most common cause of cancer death (around 2,400 people died in 2012).[74]

The connection between asbestos exposure and mesothelioma was discovered in the 1970s. In the United States, asbestos manufacture stopped in 2002. Asbestos exposure thus shifted from workers in asbestos textile mills, friction product manufacturing, cement pipe fabrication, and insulation manufacture and installation to maintenance workers in asbestos-containing buildings.[24]

Mesothelioma, though rare, has had a number of notable patients:

Although life expectancy with this disease is typically limited, there are notable survivors. In July 1982, Stephen Jay Gould, a well-regarded paleontologist, was diagnosed with peritoneal mesothelioma. After his diagnosis, Gould wrote "The Median Isn't the Message",[81] in which he argued that statistics such as median survival are useful abstractions, not destiny. Gould lived for another 20 years, eventually succumbing to cancer not linked to his mesothelioma.

Some people who were exposed to asbestos have collected damages for an asbestos-related disease, including mesothelioma. Compensation via asbestos funds or class action lawsuits is an important issue in law practices regarding mesothelioma.[citation needed]

The first lawsuits against asbestos manufacturers were in 1929. Since then, many lawsuits have been filed against asbestos manufacturers and employers, for neglecting to implement safety measures after the links between asbestos, asbestosis, and mesothelioma became known (some reports seem to place this as early as 1898). The liability resulting from the sheer number of lawsuits and people affected has reached billions of dollars.[82] The amounts and method of allocating compensation have been the source of many court cases, reaching up to the United States Supreme Court, and government attempts at resolution of existing and future cases. However, to date, the US Congress has not stepped in and there are no federal laws governing asbestos compensation.[83]In 2013, the "Furthering Asbestos Claim Transparency (FACT) Act of 2013" passed the US House of representatives and was sent to the US Senate, where it was referred to the Senate Judiciary Committee.[84] As the Senate did not vote on it before the end of the 113th Congress, it died in committee. It was revived in the 114th Congress, where it has not yet been brought before the House for a vote.[85]

The first lawsuit against asbestos manufacturers was brought in 1929. The parties settled that lawsuit, and as part of the agreement, the attorneys agreed not to pursue further cases. In 1960, an article published by Wagner et al. was seminal in establishing mesothelioma as a disease arising from exposure to asbestos.[86] The article referred to over 30 case studies of people who had suffered from mesothelioma in South Africa. Some exposures were transient and some were mine workers. Before the use of advanced microscopy techniques, malignant mesothelioma was often diagnosed as a variant form of lung cancer.[87] In 1962, McNulty reported the first diagnosed case of malignant mesothelioma in an Australian asbestos worker.[88] The worker had worked in the mill at the asbestos mine in Wittenoom from 1948 to 1950.[citation needed]

In the town of Wittenoom, asbestos-containing mine waste was used to cover schoolyards and playgrounds. In 1965, an article in the British Journal of Industrial Medicine established that people who lived in the neighbourhoods of asbestos factories and mines, but did not work in them, had contracted mesothelioma.[citation needed]

Despite proof that the dust associated with asbestos mining and milling causes asbestos-related disease, mining began at Wittenoom in 1943 and continued until 1966. In 1974, the first public warnings of the dangers of blue asbestos were published in a cover story called "Is this Killer in Your Home?" in Australia's Bulletin magazine. In 1978, the Western Australian Government decided to phase out the town of Wittenoom, following the publication of a Health Dept. booklet, "The Health Hazard at Wittenoom", containing the results of air sampling and an appraisal of worldwide medical information.[citation needed]

By 1979, the first writs for negligence related to Wittenoom were issued against CSR and its subsidiary ABA, and the Asbestos Diseases Society was formed to represent the Wittenoom victims.[citation needed]

In Leeds, England the Armley asbestos disaster involved several court cases against Turner & Newall where local residents who contracted mesothelioma demanded compensation because of the asbestos pollution from the company's factory. One notable case was that of June Hancock, who contracted the disease in 1993 and died in 1997.[89]

The WT-1 protein is overexpressed in mesothelioma and is being researched as a potential target for drugs.[11]

There are two high-confidence miRNAs that can potentially serve as biomarkers of asbestos exposure and malignant mesothelioma. Validation studies are needed to assess their relevance.[90]

Mesothelioma at Curlie

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Mesothelioma - Wikipedia

Mesothelioma – Symptoms and causes – Mayo Clinic

Overview

Malignant mesothelioma (me-zoe-thee-lee-O-muh) is a type of cancer that occurs in the thin layer of tissue that covers the majority of your internal organs (mesothelium).

Mesothelioma is an aggressive and deadly form of cancer. Mesothelioma treatments are available, but for many people with mesothelioma, a cure isn't possible.

Doctors divide mesothelioma into different types based on what part of the mesothelium is affected. Mesothelioma most often affects the tissue that surrounds the lungs (pleura). This type is called pleural mesothelioma. Other, rarer types of mesothelioma affect tissue in the abdomen (peritoneal mesothelioma), around the heart and around the testicles.

Mesothelioma care at Mayo Clinic

Signs and symptoms of mesothelioma vary depending on where the cancer occurs.

Pleural mesothelioma, which affects the tissue that surrounds the lungs, causes signs and symptoms that may include:

Peritoneal mesothelioma, which occurs in tissue in the abdomen, causes signs and symptoms that may include:

Signs and symptoms of other types of mesothelioma are unclear, since these forms of the disease are very rare.

Pericardial mesothelioma, which affects tissue that surrounds the heart, can cause signs and symptoms such as breathing difficulty and chest pains.

Mesothelioma of tunica vaginalis, which affects tissue surrounding the testicles, may be first detected as swelling or a mass on a testicle.

See your doctor if you have signs and symptoms that worry you. Signs and symptoms of mesothelioma aren't specific to this disease and, due to the rarity of mesothelioma, are more likely to be related to other conditions. If any persistent signs and symptoms seem unusual or bothersome, ask your doctor to evaluate them. Tell your doctor if you've been exposed to asbestos.

In general, cancer begins when a series of changes (mutations) happens in a cell's DNA. The DNA contains the instructions that tell a cell what to do. The mutations tell the cell to grow and multiply out of control. The abnormal cells accumulate and form a tumor.

It isn't clear what causes the initial genetic mutations that lead to mesothelioma, though researchers have identified factors that may increase the risk. It's likely that cancers form because of an interaction between many factors, such as inherited conditions, your environment, your health conditions and your lifestyle choices.

Most mesotheliomas are thought to be related to asbestos exposure. Asbestos is a mineral that's found naturally in the environment. Asbestos fibers are strong and resistant to heat, making them useful in a wide variety of applications, such as in insulation, brakes, shingles, flooring and many other products.

When asbestos is broken up, such as during the mining process or when removing asbestos insulation, dust may be created. If the dust is inhaled or swallowed, the asbestos fibers will settle in the lungs or in the stomach, where they can cause irritation that may lead to mesothelioma. Exactly how this happens isn't understood. It can take 20 to 60 years or more for mesothelioma to develop after asbestos exposure.

Most people with asbestos exposure never develop mesothelioma. This indicates that other factors may be involved in determining whether someone gets mesothelioma. For instance, you could inherit a predisposition to cancer or some other condition could increase your risk.

Factors that may increase the risk of mesothelioma include:

As pleural mesothelioma spreads in the chest, it puts pressure on the structures in that area. This can cause complications, such as:

Reducing your exposure to asbestos may lower your risk of mesothelioma.

Most people with mesothelioma were exposed to the asbestos fibers at work. Workers who may encounter asbestos fibers include:

Ask your employer whether you have a risk of asbestos exposure on the job.

Follow all safety precautions in your workplace, such as wearing protective equipment. You may also be required to shower and change out of your work clothes before taking a lunch break or going home. Talk to your doctor about other precautions you can take to protect yourself from asbestos exposure.

Older homes and buildings may contain asbestos. In many cases, it's more dangerous to remove the asbestos than it is to leave it intact. Breaking up asbestos may cause fibers to become airborne, where they can be inhaled. Consult experts trained to detect asbestos in your home. These experts may test the air in your home to determine whether the asbestos is a risk to your health. Don't attempt to remove asbestos from your home hire a qualified expert.

Jan. 15, 2019

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Mesothelioma - Symptoms and causes - Mayo Clinic

Mesothelioma – Wikipedia

Cancer associated with asbestos

Mesothelioma is a type of cancer that develops from the thin layer of tissue that covers many of the internal organs (known as the mesothelium).[9] The most common area affected is the lining of the lungs and chest wall.[1][3] Less commonly the lining of the abdomen and rarely the sac surrounding the heart,[10] or the sac surrounding the testis may be affected.[1][11] Signs and symptoms of mesothelioma may include shortness of breath due to fluid around the lung, a swollen abdomen, chest wall pain, cough, feeling tired, and weight loss.[1] These symptoms typically come on slowly.[2]

More than 80% of mesothelioma cases are caused by exposure to asbestos.[3] The greater the exposure the greater the risk.[3] As of 2013, about 125 million people worldwide have been exposed to asbestos at work.[12] High rates of disease occur in people who mine asbestos, produce products from asbestos, work with asbestos products, live with asbestos workers, or work in buildings containing asbestos.[3] Asbestos exposure and the onset of cancer are generally separated by about 40 years.[3] Washing the clothing of someone who worked with asbestos also increases the risk.[12] Other risk factors include genetics and infection with the simian virus 40.[3] The diagnosis may be suspected based on chest X-ray and CT scan findings, and is confirmed by either examining fluid produced by the cancer or by a tissue biopsy of the cancer.[2]

Prevention centers around reducing exposure to asbestos.[4] Treatment often includes surgery, radiation therapy, and chemotherapy.[5] A procedure known as pleurodesis, which involves using substances such as talc to scar together the pleura, may be used to prevent more fluid from building up around the lungs.[5] Chemotherapy often includes the medications cisplatin and pemetrexed.[2] The percentage of people that survive five years following diagnosis is on average 8% in the United States.[6]

In 2015, about 60,800 people had mesothelioma, and 32,000 died from the disease.[7][8] Rates of mesothelioma vary in different areas of the world.[3] Rates are higher in Australia, the United Kingdom, and lower in Japan.[3] It occurs in about 3,000 people per year in the United States.[13] It occurs more often in males than females.[3] Rates of disease have increased since the 1950s.[3] Diagnosis typically occurs after the age of 65 and most deaths occur around 70 years old.[3] The disease was rare before the commercial use of asbestos.[3]

Symptoms or signs of mesothelioma may not appear until 20 to 50 years (or more) after exposure to asbestos. Shortness of breath, cough, and pain in the chest due to an accumulation of fluid in the pleural space (pleural effusion) are often symptoms of pleural mesothelioma.[14]

Mesothelioma that affects the pleura can cause these signs and symptoms:[14]

In severe cases, the person may have many tumor masses. The individual may develop a pneumothorax, or collapse of the lung. The disease may metastasize, or spread to other parts of the body.

The most common symptoms of peritoneal mesothelioma are abdominal swelling and pain due to ascites (a buildup of fluid in the abdominal cavity). Other features may include weight loss, fever, night sweats, poor appetite, vomiting, constipation, and umbilical hernia.[15] If the cancer has spread beyond the mesothelium to other parts of the body, symptoms may include pain, trouble swallowing, or swelling of the neck or face.[citation needed]These symptoms may be caused by mesothelioma or by other, less serious conditions.

Tumors that affect the abdominal cavity often do not cause symptoms until they are at a late stage. Symptoms include:[citation needed]

Pericardial mesothelioma is not well characterized, but observed cases have included cardiac symptoms, specifically constrictive pericarditis, heart failure, pulmonary embolism, and cardiac tamponade. They have also included nonspecific symptoms, including substernal chest pain, orthopnea (shortness of breath when lying flat), and cough. These symptoms are caused by the tumor encasing or infiltrating the heart.[10]

In severe cases of the disease, the following signs and symptoms may be present:[citation needed]

If a mesothelioma forms metastases, these most commonly involve the liver, adrenal gland, kidney, or other lung.[16]

Working with asbestos is the most common risk factor for mesothelioma.[17] However, mesothelioma has been reported in some individuals without any known exposure to asbestos. Tentative evidence also raises concern about carbon-fibre nanotubes.[18][19]

The incidence of mesothelioma has been found to be higher in populations living near naturally occurring asbestos. People can be exposed to naturally occurring asbestos in areas where mining or road construction is occurring, or when the asbestos-containing rock is naturally weathered. Another common route of exposure is through asbestos-containing soil, which is used to whitewash, plaster, and roof houses in Greece.[12] In central Cappadocia, Turkey, mesothelioma was causing 50% of all deaths in three small villagesTuzky, Karain, and Sarhdr. Initially, this was attributed to erionite. Environmental exposure to asbestos has caused mesothelioma in places other than Turkey, including Corsica, Greece, Cyprus, China, and California.[12][20][21] In the northern Greek mountain town of Metsovo, this exposure had resulted in mesothelioma incidence around 300 times more than expected in asbestos-free populations, and was associated with very frequent pleural calcification known as "Metsovo Lung".[22][23]

The documented presence of asbestos fibers in water supplies and food products has fostered concerns about the possible impact of long-term and, as yet, unknown exposure of the general population to these fibers.[citation needed]

Exposure to talc is also a risk factor for mesothelioma; exposure can affect those who live near talc mines, work in talc mines, or work in talc mills.[24]

In the United States, asbestos is considered the major cause of malignant mesothelioma[25] and has been considered "indisputably"[26] associated with the development of mesothelioma. Indeed, the relationship between asbestos and mesothelioma is so strong that many consider mesothelioma a signal or sentinel tumor.[27][28][29][30] A history of asbestos exposure exists in most cases.

Pericardial mesothelioma may not be associated with asbestos exposure.[10]

Asbestos was known in antiquity, but it was not mined and widely used commercially until the late 19th century. Its use greatly increased during World War II. Since the early 1940s, millions of American workers have been exposed to asbestos dust. Initially, the risks associated with asbestos exposure were not publicly known. However, an increased risk of developing mesothelioma was later found among naval personnel (e.g., Navy, Marine Corps, and Coast Guard), shipyard workers, people who work in asbestos mines and mills, producers of asbestos products, workers in the heating and construction industries, and other tradespeople. Today, the official position of the U.S. Occupational Safety and Health Administration (OSHA) and the U.S. EPA is that protections and "permissible exposure limits" required by U.S. regulations, while adequate to prevent most asbestos-related non-malignant disease, are not adequate to prevent or protect against asbestos-related cancers such as mesothelioma.[31] Likewise, the British Government's Health and Safety Executive (HSE) states formally that any threshold for exposure to asbestos must be at a very low level and it is widely agreed that if any such threshold does exist at all, then it cannot currently be quantified. For practical purposes, therefore, HSE assumes that no such "safe" threshold exists. Others have noted as well that there is no evidence of a threshold level below which there is no risk of mesothelioma.[32] There appears to be a linear, doseresponse relationship, with increasing dose producing increasing risk of disease.[33] Nevertheless, mesothelioma may be related to brief, low level or indirect exposures to asbestos.[26] The dose necessary for effect appears to be lower for asbestos-induced mesothelioma than for pulmonary asbestosis or lung cancer.[26] Again, there is no known safe level of exposure to asbestos as it relates to increased risk of mesothelioma.

The time from first exposure to onset of the disease, is between 25 and 70 years.[34] It is virtually never less than fifteen years and peaks at 3040 years.[26][35] The duration of exposure to asbestos causing mesothelioma can be short. For example, cases of mesothelioma have been documented with only 13 months of exposure.[36][37]

Exposure to asbestos fibers has been recognized as an occupational health hazard since the early 20th century. Numerous epidemiological studies have associated occupational exposure to asbestos with the development of pleural plaques, diffuse pleural thickening, asbestosis, carcinoma of the lung and larynx, gastrointestinal tumors, and diffuse malignant mesothelioma of the pleura and peritoneum. Asbestos has been widely used in many industrial products, including cement, brake linings, gaskets, roof shingles, flooring products, textiles, and insulation.[38]

Commercial asbestos mining at Wittenoom, Western Australia, took place from 1937 to 1966. The first case of mesothelioma in the town occurred in 1960. The second case was in 1969, and new cases began to appear more frequently thereafter. The lag time between initial exposure to asbestos and the development of mesothelioma varied from 12 years 9 months up to 58 years.[39] A cohort study of miners employed at the mine reported that 85 deaths attributable to mesothelioma had occurred by 1985. By 1994, 539 reported deaths due to mesothelioma had been reported in Western Australia.[citation needed]

Occupational exposure to asbestos in the United States mainly occurs when people are maintaining buildings that already have asbestos. Approximately 1.3 million US workers are exposed to asbestos annually; in 2002, an estimated 44,000 miners were potentially exposed to asbestos.[24]

Family members and others living with asbestos workers have an increased risk of developing mesothelioma, and possibly other asbestos-related diseases.[11][40][41] This risk may be the result of exposure to asbestos dust brought home on the clothing and hair of asbestos workers via washing a worker's clothes or coming into contact with asbestos-contaminated work clothing.[12][24] To reduce the chance of exposing family members to asbestos fibres, asbestos workers are usually required to shower and change their clothing before leaving the workplace.[citation needed]

Many building materials used in both public and domestic premises prior to the banning of asbestos may contain asbestos. Those performing renovation works or DIY activities may expose themselves to asbestos dust. In the UK, use of chrysotile asbestos was banned at the end of 1999. Brown and blue asbestos were banned in the UK around 1985. Buildings built or renovated prior to these dates may contain asbestos materials.[citation needed]

In a recent research carried on white American population in 2012, it was found that people with a germline mutation in their BAP1 gene are at higher risk of developing mesothelioma and uveal melanoma.[42]

Erionite is a zeolite mineral with similar properties to asbestos and is known to cause mesothelioma.[11] Detailed epidemiological investigation has shown that erionite causes mesothelioma mostly in families with a genetic predisposition.[12][20][21] Erionite is found in deposits in the Western United States, where it is used in gravel for road surfacing, and in Turkey, where it is used to construct homes. In Turkey, the United States, and Mexico, erionite has been associated with mesothelioma and has thus been designated a "known human carcinogen" by the US National Toxicology Program.[21]

In rare cases, mesothelioma has also been associated with irradiation of the chest or abdomen, intrapleural thorium dioxide (thorotrast) as a contrast medium, and inhalation of other fibrous silicates, such as erionite or talc.[11][24] Some studies suggest that simian virus 40 (SV40) may act as a cofactor in the development of mesothelioma.[24] This has been confirmed in animal studies,[43][44] but studies in humans are inconclusive.[43][45][46]

The mesothelium consists of a single layer of flattened to cuboidal cells forming the epithelial lining of the serous cavities of the body including the peritoneal, pericardial and pleural cavities. Deposition of asbestos fibers in the parenchyma of the lung may result in the penetration of the visceral pleura from where the fiber can then be carried to the pleural surface, thus leading to the development of malignant mesothelial plaques. The processes leading to the development of peritoneal mesothelioma remain unresolved, although it has been proposed that asbestos fibers from the lung are transported to the abdomen and associated organs via the lymphatic system. Additionally, asbestos fibers may be deposited in the gut after ingestion of sputum contaminated with asbestos fibers.[citation needed]

Pleural contamination with asbestos or other mineral fibers has been shown to cause cancer. Long thin asbestos fibers (blue asbestos, amphibole fibers) are more potent carcinogens than "feathery fibers" (chrysotile or white asbestos fibers).[26] However, there is now evidence that smaller particles may be more dangerous than the larger fibers. They remain suspended in the air where they can be inhaled, and may penetrate more easily and deeper into the lungs. "We probably will find out a lot more about the health aspects of asbestos from [the World Trade Center attack], unfortunately," said Dr. Alan Fein, chief of pulmonary and critical-care medicine at North Shore-Long Island Jewish Health System.[47]

Mesothelioma development in rats has been demonstrated following intra-pleural inoculation of phosphorylated chrysotile fibers. It has been suggested that in humans, transport of fibers to the pleura is critical to the pathogenesis of mesothelioma. This is supported by the observed recruitment of significant numbers of macrophages and other cells of the immune system to localized lesions of accumulated asbestos fibers in the pleural and peritoneal cavities of rats. These lesions continued to attract and accumulate macrophages as the disease progressed, and cellular changes within the lesion culminated in a morphologically malignant tumor.[citation needed]

Experimental evidence suggests that asbestos acts as a complete carcinogen with the development of mesothelioma occurring in sequential stages of initiation and promotion. The molecular mechanisms underlying the malignant transformation of normal mesothelial cells by asbestos fibers remain unclear despite the demonstration of its oncogenic capabilities (see next-but-one paragraph). However, complete in vitro transformation of normal human mesothelial cells to a malignant phenotype following exposure to asbestos fibers has not yet been achieved. In general, asbestos fibers are thought to act through direct physical interactions with the cells of the mesothelium in conjunction with indirect effects following interaction with inflammatory cells such as macrophages.[citation needed]

Analysis of the interactions between asbestos fibers and DNA has shown that phagocytosed fibers are able to make contact with chromosomes, often adhering to the chromatin fibers or becoming entangled within the chromosome. This contact between the asbestos fiber and the chromosomes or structural proteins of the spindle apparatus can induce complex abnormalities. The most common abnormality is monosomy of chromosome 22. Other frequent abnormalities include structural rearrangement of 1p, 3p, 9p and 6q chromosome arms.[citation needed]

Common gene abnormalities in mesothelioma cell lines include deletion of the tumor suppressor genes:[citation needed]

Asbestos has also been shown to mediate the entry of foreign DNA into target cells. Incorporation of this foreign DNA may lead to mutations and oncogenesis by several possible mechanisms:

Several genes are commonly mutated in mesothelioma, and may be prognostic factors. These include epidermal growth factor receptor (EGFR) and C-Met, receptor tyrosine kinases which are overexpressed in many mesotheliomas. Some association has been found with EGFR and epithelioid histology but no clear association has been found between EGFR overexpression and overall survival. Expression of AXL receptor tyrosine kinase is a negative prognostic factor. Expression of PDGFRB is a positive prognostic factor.[49] In general, mesothelioma is characterized by loss of function in tumor suppressor genes, rather than by an overexpression or gain of function in oncogenes.[50]

As an environmentally triggered malignancy, mesothelioma tumors have been found to be polyclonal in origin, by performing a X-inactivation based assay on epitheloid and biphasic tumors obtained from female patients.[51] These results suggest that an environmental factor, most likely asbestos exposure, may damage and transform a group of cells in the tissue, resulting in a population of tumor cells that are, albeit only slightly, genetically different.[52]

Asbestos fibers have been shown to alter the function and secretory properties of macrophages, ultimately creating conditions which favour the development of mesothelioma. Following asbestos phagocytosis, macrophages generate increased amounts of hydroxyl radicals, which are normal by-products of cellular anaerobic metabolism. However, these free radicals are also known clastogenic (chromosome-breaking) and membrane-active agents thought to promote asbestos carcinogenicity. These oxidants can participate in the oncogenic process by directly and indirectly interacting with DNA, modifying membrane-associated cellular events, including oncogene activation and perturbation of cellular antioxidant defences.[citation needed]

Asbestos also may possess immunosuppressive properties. For example, chrysotile fibres have been shown to depress the in vitro proliferation of phytohemagglutinin-stimulated peripheral blood lymphocytes, suppress natural killer cell lysis and significantly reduce lymphokine-activated killer cell viability and recovery. Furthermore, genetic alterations in asbestos-activated macrophages may result in the release of potent mesothelial cell mitogens such as platelet-derived growth factor (PDGF) and transforming growth factor- (TGF-) which in turn, may induce the chronic stimulation and proliferation of mesothelial cells after injury by asbestos fibres.[citation needed]

Diagnosis of mesothelioma can be suspected with imaging but is confirmed with biopsy. It must be clinically and histologically differentiated from other pleural and pulmonary malignancies, including reactive pleural disease, primary lung carcinoma, pleural metastases of other cancers, and other primary pleural cancers.[11]Primary pericardial mesothelioma is often diagnosed after it has metastasized to lymph nodes or the lungs.[10]

Diagnosing mesothelioma is often difficult because the symptoms are similar to those of a number of other conditions. Diagnosis begins with a review of the patient's medical history. A history of exposure to asbestos may increase clinical suspicion for mesothelioma. A physical examination is performed, followed by chest X-ray and often lung function tests. The X-ray may reveal pleural thickening commonly seen after asbestos exposure and increases suspicion of mesothelioma.[14] A CT (or CAT) scan or an MRI is usually performed. If a large amount of fluid is present, abnormal cells may be detected by cytopathology if this fluid is aspirated with a syringe.[10] For pleural fluid, this is done by thoracentesis or tube thoracostomy (chest tube); for ascites, with paracentesis or ascitic drain; and for pericardial effusion with pericardiocentesis. While absence of malignant cells on cytology does not completely exclude mesothelioma, it makes it much more unlikely, especially if an alternative diagnosis can be made (e.g., tuberculosis, heart failure).[citation needed] However, with primary pericardial mesothelioma, pericardial fluid may not contain malignant cells and a tissue biopsy is more useful in diagnosis.[10] Using conventional cytology diagnosis of malignant mesothelioma is difficult, but immunohistochemistry has greatly enhanced the accuracy of cytology.[citation needed]

Generally, a biopsy is needed to confirm a diagnosis of malignant mesothelioma. A doctor removes a sample of tissue for examination under a microscope by a pathologist. A biopsy may be done in different ways, depending on where the abnormal area is located. If the cancer is in the chest, the doctor may perform a thoracoscopy. In this procedure, the doctor makes a small cut through the chest wall and puts a thin, lighted tube called a thoracoscope into the chest between two ribs. Thoracoscopy allows the doctor to look inside the chest and obtain tissue samples. Alternatively, the chest surgeon might directly open the chest (thoracotomy). If the cancer is in the abdomen, the doctor may perform a laparoscopy. To obtain tissue for examination, the doctor makes a small incision in the abdomen and inserts a special instrument into the abdominal cavity. If these procedures do not yield enough tissue, an open surgical procedure may be necessary.[citation needed]

Immunohistochemical studies play an important role for the pathologist in differentiating malignant mesothelioma from neoplastic mimics, such as breast or lung cancer that has metastasized to the pleura. There are numerous tests and panels available, but no single test is perfect for distinguishing mesothelioma from carcinoma or even benign versus malignant. The positive markers indicate that mesothelioma is present; if other markers are positive it may indicate another type of cancer, such as breast or lung adenocarcinoma. Calretinin is a particularly important marker in distinguishing mesothelioma from metastatic breast or lung cancer.[11]

There are three main histological subtypes of malignant mesothelioma: epithelioid, sarcomatous, and biphasic. Epithelioid and biphasic mesothelioma make up approximately 75-95% of mesotheliomas and have been well characterized histologically, whereas sarcomatous mesothelioma has not been studied extensively. Most mesotheliomas express high levels of cytokeratin 5 regardless of subtype.[11]

Epithelioid mesothelioma is characterized by high levels of calretinin.[11]

Sarcomatous mesothelioma does not express high levels of calretinin.[11]

Other morphological subtypes have been described:

Staging of mesothelioma is based on the recommendation by the International Mesothelioma Interest Group.[53] TNM classification of the primary tumor, lymph node involvement, and distant metastasis is performed. Mesothelioma is staged IaIV (one-A to four) based on the TNM status.[53][54]

Mesothelioma can be prevented in most cases by preventing exposure to asbestos. The US National Institute for Occupational Safety and Health maintains a recommended exposure limit of 0.1 asbestos fiber per cubic centimeter.[24]

There is no universally agreed protocol for screening people who have been exposed to asbestos. Screening tests might diagnose mesothelioma earlier than conventional methods thus improving the survival prospects for patients. The serum osteopontin level might be useful in screening asbestos-exposed people for mesothelioma. The level of soluble mesothelin-related protein is elevated in the serum of about 75% of patients at diagnosis and it has been suggested that it may be useful for screening.[55] Doctors have begun testing the Mesomark assay which measures levels of soluble mesothelin-related proteins (SMRPs) released by mesothelioma cells.[56]

Mesothelioma is generally resistant to radiation and chemotherapy treatment. Long-term survival and cures are exceedingly rare.[11] Treatment of malignant mesothelioma at earlier stages has a better prognosis. Clinical behavior of the malignancy is affected by several factors including the continuous mesothelial surface of the pleural cavity which favors local metastasis via exfoliated cells, invasion to underlying tissue and other organs within the pleural cavity, and the extremely long latency period between asbestos exposure and development of the disease. The histological subtype and the patient's age and health status also help predict prognosis. The epithelioid histology responds better to treatment and has a survival advantage over sarcomatoid histology.[57]

Surgery, by itself, has proved disappointing. In one large series, the median survival with surgery (including extrapleural pneumonectomy) was only 11.7 months.[58] However, research indicates varied success when used in combination with radiation and chemotherapy (Duke, 2008), or with one of the latter. A pleurectomy/decortication is the most common surgery, in which the lining of the chest is removed. Less common is an extrapleural pneumonectomy (EPP), in which the lung, lining of the inside of the chest, the hemi-diaphragm and the pericardium are removed.[citation needed] In localized pericardial mesothelioma, pericardectomy can be curative; when the tumor has metastasized, pericardectomy is a palliative care option. The entire tumor is not often able to be removed.[10]

For patients with localized disease, and who can tolerate a radical surgery, radiation can be given post-operatively as a consolidative treatment. The entire hemithorax is treated with radiation therapy, often given simultaneously with chemotherapy. Delivering radiation and chemotherapy after a radical surgery has led to extended life expectancy in selected patient populations. It can also induce severe side-effects, including fatal pneumonitis.[59] As part of a curative approach to mesothelioma, radiotherapy is commonly applied to the sites of chest drain insertion, in order to prevent growth of the tumor along the track in the chest wall.[citation needed]

Although mesothelioma is generally resistant to curative treatment with radiotherapy alone, palliative treatment regimens are sometimes used to relieve symptoms arising from tumor growth, such as obstruction of a major blood vessel. Radiation therapy, when given alone with curative intent, has never been shown to improve survival from mesothelioma. The necessary radiation dose to treat mesothelioma that has not been surgically removed would be beyond human tolerance.[citation needed] Radiotherapy is of some use in pericardial mesothelioma.[10]

Chemotherapy is the only treatment for mesothelioma that has been proven to improve survival in randomised and controlled trials. The landmark study published in 2003 by Vogelzang and colleagues compared cisplatin chemotherapy alone with a combination of cisplatin and pemetrexed (brand name Alimta) chemotherapy in patients who had not received chemotherapy for malignant pleural mesothelioma previously and were not candidates for more aggressive "curative" surgery.[60] This trial was the first to report a survival advantage from chemotherapy in malignant pleural mesothelioma, showing a statistically significant improvement in median survival from 10 months in the patients treated with cisplatin alone to 13.3 months in the group of patients treated with cisplatin in the combination with pemetrexed and who also received supplementation with folate and vitamin B12. Vitamin supplementation was given to most patients in the trial and pemetrexed related side effects were significantly less in patients receiving pemetrexed when they also received daily oral folate 500mcg and intramuscular vitamin B12 1000mcg every 9 weeks compared with patients receiving pemetrexed without vitamin supplementation. The objective response rate increased from 20% in the cisplatin group to 46% in the combination pemetrexed group. Some side effects such as nausea and vomiting, stomatitis, and diarrhoea were more common in the combination pemetrexed group but only affected a minority of patients and overall the combination of pemetrexed and cisplatin was well tolerated when patients received vitamin supplementation; both quality of life and lung function tests improved in the combination pemetrexed group. In February 2004, the United States Food and Drug Administration approved pemetrexed for treatment of malignant pleural mesothelioma. However, there are still unanswered questions about the optimal use of chemotherapy, including when to start treatment, and the optimal number of cycles to give.[citation needed] Cisplatin and pemetrexed together give patients a median survival of 12.1 months.[11]

Cisplatin in combination with raltitrexed has shown an improvement in survival similar to that reported for pemetrexed in combination with cisplatin, but raltitrexed is no longer commercially available for this indication. For patients unable to tolerate pemetrexed, cisplatin in combination with gemcitabine or vinorelbine is an alternative, or vinorelbine on its own, although a survival benefit has not been shown for these drugs. For patients in whom cisplatin cannot be used, carboplatin can be substituted but non-randomised data have shown lower response rates and high rates of haematological toxicity for carboplatin-based combinations, albeit with similar survival figures to patients receiving cisplatin.[61]

In January 2009, the United States FDA approved using conventional therapies such as surgery in combination with radiation and or chemotherapy on stage I or II Mesothelioma after research conducted by a nationwide study by Duke University concluded an almost 50 point increase in remission rates.[citation needed]

In pericardial mesothelioma, chemotherapy - typically adriamycin and/or cisplatin - is primarily used to shrink the tumor and is not curative.[10]

Treatment regimens involving immunotherapy have yielded variable results. For example, intrapleural inoculation of Bacillus Calmette-Gurin (BCG) in an attempt to boost the immune response, was found to be of no benefit to the patient (while it may benefit patients with bladder cancer). Mesothelioma cells proved susceptible to in vitro lysis by LAK cells following activation by interleukin-2 (IL-2), but patients undergoing this particular therapy experienced major side effects. Indeed, this trial was suspended in view of the unacceptably high levels of IL-2 toxicity and the severity of side effects such as fever and cachexia. Nonetheless, other trials involving interferon alpha have proved more encouraging with 20% of patients experiencing a greater than 50% reduction in tumor mass combined with minimal side effects.[citation needed]

This technique is used in conjunction with surgery,[62] including in patients with malignant pleural mesothelioma.[63] The surgeon removes as much of the tumor as possible followed by the direct administration of a chemotherapy agent, heated to between 40 and 48C, in the abdomen. The fluid is perfused for 60 to 120 minutes and then drained. High concentrations of selected drugs are then administered into the abdominal and pelvic surfaces. Heating the chemotherapy treatment increases the penetration of the drugs into tissues. Also, heating itself damages the malignant cells more than the normal cells.[citation needed]

All of the standard approaches to treating solid tumorsradiation, chemotherapy, and surgeryhave been investigated in patients with malignant pleural mesothelioma. Although surgery, by itself, is not very effective, surgery combined with adjuvant chemotherapy and radiation (trimodality therapy) has produced significant survival extension (314 years) among patients with favorable prognostic factors.[64] However, other large series of examining multimodality treatment have only demonstrated modest improvement in survival (median survival 14.5 months and only 29.6% surviving 2 years).[58] Reducing the bulk of the tumor with cytoreductive surgery is key to extending survival. Two surgeries have been developed: extrapleural pneumonectomy and pleurectomy/decortication. The indications for performing these operations are unique. The choice of operation namely depends on the size of the patient's tumor. This is an important consideration because tumor volume has been identified as a prognostic factor in mesothelioma.[65] Pleurectomy/decortication spares the underlying lung and is performed in patients with early stage disease when the intention is to remove all gross visible tumor (macroscopic complete resection), not simply palliation.[66] Extrapleural pneumonectomy is a more extensive operation that involves resection of the parietal and visceral pleurae, underlying lung, ipsilateral (same side) diaphragm, and ipsilateral pericardium. This operation is indicated for a subset of patients with more advanced tumors, who can tolerate a pneumonectomy.[67]

Mesothelioma often has a poor prognosis. Typical survival despite surgery is between 12 and 21 months depending on the stage of disease at diagnosis with about 7.5% of people surviving for 5 years.[68]

Women, young people, people with low-stage cancers, and people with epithelioid cancers have better prognoses.[11] Negative prognostic factors include sarcomatoid or biphasic histology, high platelet counts (above 400,000), age over 50 years, white blood cell counts above 15.5, low glucose levels in the pleural fluid, low albumin levels, and high fibrinogen levels. Several markers are under investigation as prognostic factors, including nuclear grade, and serum c-reactive protein. Long-term survival is rare.[49]

Pericardial mesothelioma has a 10-month median survival time.[10]

In peritoneal mesothelioma, high expression of WT-1 protein indicates a worse prognosis.[11]

Although reported incidence rates have increased in the past 20 years, mesothelioma is still a relatively rare cancer. The incidence rate varies from one country to another, from a low rate of less than 1 per 1,000,000 in Tunisia and Morocco, to the highest rate in Britain, Australia and Belgium: 30 per 1,000,000 per year.[69] For comparison, populations with high levels of smoking can have a lung cancer incidence of over 1,000 per 1,000,000. Incidence of malignant mesothelioma currently ranges from about 7 to 40 per 1,000,000 in industrialized Western nations, depending on the amount of asbestos exposure of the populations during the past several decades.[70] Worldwide incidence is estimated at 1-6 per 1,000,000.[11] Incidence of mesothelioma lags behind that of asbestosis due to the longer time it takes to develop; due to the cessation of asbestos use in developed countries, mesothelioma incidence is expected to decrease.[24] Incidence is expected to continue increasing in developing countries due to continuing use of asbestos.[11] Mesothelioma occurs more often in men than in women and risk increases with age, but this disease can appear in either men or women at any age. Approximately one fifth to one third of all mesotheliomas are peritoneal.[citation needed] Less than 5% of mesotheliomas are pericardial. The prevalence of pericardial mesothelioma is less than 0.002%; it is more common in men than women. It typically occurs in a person's 50s-70s.[10][71]

Between 1940 and 1979, approximately 27.5 million people were occupationally exposed to asbestos in the United States.[72] Between 1973 and 1984, the incidence of pleural mesothelioma among Caucasian males increased 300%. From 1980 to the late 1990s, the death rate from mesothelioma in the USA increased from 2,000 per year to 3,000, with men four times more likely to acquire it than women.[citation needed] More than 80% of mesotheliomas are caused by asbestos exposure.[11]

The incidence of peritoneal mesothelioma is 0.53.0 per million per year in men, and 0.22.0 per million per year in women.[73]

Mesothelioma accounts for less than 1% of all cancers diagnosed in the UK, (around 2,600 people were diagnosed with the disease in 2011), and it is the seventeenth most common cause of cancer death (around 2,400 people died in 2012).[74]

The connection between asbestos exposure and mesothelioma was discovered in the 1970s. In the United States, asbestos manufacture stopped in 2002. Asbestos exposure thus shifted from workers in asbestos textile mills, friction product manufacturing, cement pipe fabrication, and insulation manufacture and installation to maintenance workers in asbestos-containing buildings.[24]

Mesothelioma, though rare, has had a number of notable patients:

Although life expectancy with this disease is typically limited, there are notable survivors. In July 1982, Stephen Jay Gould, a well-regarded paleontologist, was diagnosed with peritoneal mesothelioma. After his diagnosis, Gould wrote "The Median Isn't the Message",[81] in which he argued that statistics such as median survival are useful abstractions, not destiny. Gould lived for another 20 years, eventually succumbing to cancer not linked to his mesothelioma.

Some people who were exposed to asbestos have collected damages for an asbestos-related disease, including mesothelioma. Compensation via asbestos funds or class action lawsuits is an important issue in law practices regarding mesothelioma.[citation needed]

The first lawsuits against asbestos manufacturers were in 1929. Since then, many lawsuits have been filed against asbestos manufacturers and employers, for neglecting to implement safety measures after the links between asbestos, asbestosis, and mesothelioma became known (some reports seem to place this as early as 1898). The liability resulting from the sheer number of lawsuits and people affected has reached billions of dollars.[82] The amounts and method of allocating compensation have been the source of many court cases, reaching up to the United States Supreme Court, and government attempts at resolution of existing and future cases. However, to date, the US Congress has not stepped in and there are no federal laws governing asbestos compensation.[83]In 2013, the "Furthering Asbestos Claim Transparency (FACT) Act of 2013" passed the US House of representatives and was sent to the US Senate, where it was referred to the Senate Judiciary Committee.[84] As the Senate did not vote on it before the end of the 113th Congress, it died in committee. It was revived in the 114th Congress, where it has not yet been brought before the House for a vote.[85]

The first lawsuit against asbestos manufacturers was brought in 1929. The parties settled that lawsuit, and as part of the agreement, the attorneys agreed not to pursue further cases. In 1960, an article published by Wagner et al. was seminal in establishing mesothelioma as a disease arising from exposure to asbestos.[86] The article referred to over 30 case studies of people who had suffered from mesothelioma in South Africa. Some exposures were transient and some were mine workers. Before the use of advanced microscopy techniques, malignant mesothelioma was often diagnosed as a variant form of lung cancer.[87] In 1962, McNulty reported the first diagnosed case of malignant mesothelioma in an Australian asbestos worker.[88] The worker had worked in the mill at the asbestos mine in Wittenoom from 1948 to 1950.[citation needed]

In the town of Wittenoom, asbestos-containing mine waste was used to cover schoolyards and playgrounds. In 1965, an article in the British Journal of Industrial Medicine established that people who lived in the neighbourhoods of asbestos factories and mines, but did not work in them, had contracted mesothelioma.[citation needed]

Despite proof that the dust associated with asbestos mining and milling causes asbestos-related disease, mining began at Wittenoom in 1943 and continued until 1966. In 1974, the first public warnings of the dangers of blue asbestos were published in a cover story called "Is this Killer in Your Home?" in Australia's Bulletin magazine. In 1978, the Western Australian Government decided to phase out the town of Wittenoom, following the publication of a Health Dept. booklet, "The Health Hazard at Wittenoom", containing the results of air sampling and an appraisal of worldwide medical information.[citation needed]

By 1979, the first writs for negligence related to Wittenoom were issued against CSR and its subsidiary ABA, and the Asbestos Diseases Society was formed to represent the Wittenoom victims.[citation needed]

In Leeds, England the Armley asbestos disaster involved several court cases against Turner & Newall where local residents who contracted mesothelioma demanded compensation because of the asbestos pollution from the company's factory. One notable case was that of June Hancock, who contracted the disease in 1993 and died in 1997.[89]

The WT-1 protein is overexpressed in mesothelioma and is being researched as a potential target for drugs.[11]

There are two high-confidence miRNAs that can potentially serve as biomarkers of asbestos exposure and malignant mesothelioma. Validation studies are needed to assess their relevance.[90]

Mesothelioma at Curlie

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Mesothelioma - Wikipedia

Mesothelioma – Symptoms and causes – Mayo Clinic

Overview

Malignant mesothelioma (me-zoe-thee-lee-O-muh) is a type of cancer that occurs in the thin layer of tissue that covers the majority of your internal organs (mesothelium).

Mesothelioma is an aggressive and deadly form of cancer. Mesothelioma treatments are available, but for many people with mesothelioma, a cure isn't possible.

Doctors divide mesothelioma into different types based on what part of the mesothelium is affected. Mesothelioma most often affects the tissue that surrounds the lungs (pleura). This type is called pleural mesothelioma. Other, rarer types of mesothelioma affect tissue in the abdomen (peritoneal mesothelioma), around the heart and around the testicles.

Mesothelioma care at Mayo Clinic

Signs and symptoms of mesothelioma vary depending on where the cancer occurs.

Pleural mesothelioma, which affects the tissue that surrounds the lungs, causes signs and symptoms that may include:

Peritoneal mesothelioma, which occurs in tissue in the abdomen, causes signs and symptoms that may include:

Signs and symptoms of other types of mesothelioma are unclear, since these forms of the disease are very rare.

Pericardial mesothelioma, which affects tissue that surrounds the heart, can cause signs and symptoms such as breathing difficulty and chest pains.

Mesothelioma of tunica vaginalis, which affects tissue surrounding the testicles, may be first detected as swelling or a mass on a testicle.

See your doctor if you have signs and symptoms that worry you. Signs and symptoms of mesothelioma aren't specific to this disease and, due to the rarity of mesothelioma, are more likely to be related to other conditions. If any persistent signs and symptoms seem unusual or bothersome, ask your doctor to evaluate them. Tell your doctor if you've been exposed to asbestos.

In general, cancer begins when a series of changes (mutations) happens in a cell's DNA. The DNA contains the instructions that tell a cell what to do. The mutations tell the cell to grow and multiply out of control. The abnormal cells accumulate and form a tumor.

It isn't clear what causes the initial genetic mutations that lead to mesothelioma, though researchers have identified factors that may increase the risk. It's likely that cancers form because of an interaction between many factors, such as inherited conditions, your environment, your health conditions and your lifestyle choices.

Most mesotheliomas are thought to be related to asbestos exposure. Asbestos is a mineral that's found naturally in the environment. Asbestos fibers are strong and resistant to heat, making them useful in a wide variety of applications, such as in insulation, brakes, shingles, flooring and many other products.

When asbestos is broken up, such as during the mining process or when removing asbestos insulation, dust may be created. If the dust is inhaled or swallowed, the asbestos fibers will settle in the lungs or in the stomach, where they can cause irritation that may lead to mesothelioma. Exactly how this happens isn't understood. It can take 20 to 60 years or more for mesothelioma to develop after asbestos exposure.

Most people with asbestos exposure never develop mesothelioma. This indicates that other factors may be involved in determining whether someone gets mesothelioma. For instance, you could inherit a predisposition to cancer or some other condition could increase your risk.

Factors that may increase the risk of mesothelioma include:

As pleural mesothelioma spreads in the chest, it puts pressure on the structures in that area. This can cause complications, such as:

Reducing your exposure to asbestos may lower your risk of mesothelioma.

Most people with mesothelioma were exposed to the asbestos fibers at work. Workers who may encounter asbestos fibers include:

Ask your employer whether you have a risk of asbestos exposure on the job.

Follow all safety precautions in your workplace, such as wearing protective equipment. You may also be required to shower and change out of your work clothes before taking a lunch break or going home. Talk to your doctor about other precautions you can take to protect yourself from asbestos exposure.

Older homes and buildings may contain asbestos. In many cases, it's more dangerous to remove the asbestos than it is to leave it intact. Breaking up asbestos may cause fibers to become airborne, where they can be inhaled. Consult experts trained to detect asbestos in your home. These experts may test the air in your home to determine whether the asbestos is a risk to your health. Don't attempt to remove asbestos from your home hire a qualified expert.

Jan. 15, 2019

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Mesothelioma - Symptoms and causes - Mayo Clinic

Mesothelioma: What Is Malignant Mesothelioma Cancer?

Causes

Exposure to asbestos is the main cause of the cancer.

Mesothelioma develops when a person ingests asbestos, and it causes changes to a persons DNA.

Our genes, which are made of DNA, control how cells grow, multiply and die. Changes in our genes may cause cells to divide out of control and may lead to cancer.

Tumors also can be benign (noncancerous). But when tumors are cancerous, doctors call the disease malignant mesothelioma. It is often shortened to mesothelioma.

Common mesothelioma symptoms include:

These mesothelioma symptoms usually do not show until tumors have grown and spread. Mesothelioma latency is 20-50 years. Thats how long it takes from initial exposure to accurate diagnosis. For that reason, many people with mesothelioma are in their 60s or 70s.

You should talk to a mesothelioma specialist soon if you have a history of asbestos exposure and experience these symptoms. An early mesothelioma diagnosis may improve your prognosis and life expectancy.

We've been helping patients and families get answers to their questions about mesothelioma since 2006. Let us help you.

Oncologists name each type of mesothelioma by the location in the body where it develops.

The pleural and peritoneal types of mesothelioma are the most common. Pericardial accounts for 1 percent of cases. Another rare type is testicular mesothelioma. It represents less than 1 percent of all mesotheliomas.

Prognosis, symptoms and treatment options vary by type.

Asbestos use in the military was widespread from 1940 to 1980. Veterans from all branches of the U.S. armed forces were at risk of exposure. Navy veterans are most at risk. This branch used the largest quantity of asbestos products.

More than 75 occupations have exposed workers to asbestos. Auto mechanics, textile workers, steel mill workers, construction workers and firefighters are among the most at risk.

Asbestos workers unknowingly carried asbestos fibers on their body and clothing. This resulted in secondary asbestos exposure among residents such as women and children.

The factors that most affect prognosis are stage and cell type. But age, gender and exposure history also affect outlook.

For example, younger patients and women have a better mesothelioma prognosis than older men. People diagnosed with the peritoneal mesothelioma type also have a higher chance of survival. The life expectancy for most patients is about 12 months after diagnosis.

Those who can undergo multimodal therapy, which is a combination of two or more treatments, have an improved prognosis.

Patients can improve prognosis by eating a nutrient-rich diet, undergoing cancer treatments and staying healthy.

Cell types and their role in prognosis and life expectancy:

The cancer is localized. Surgery is most effective at this stage. Survival rate is higher. Median life expectancy at stage 1 is 22.2 months.

Tumors have started to spread from the original location into adjacent structures. Surgery is still an option. Median life expectancy at stage 2 is 20 months.

Cancer has progressed to a more advanced stage with spread into the regional lymph nodes. Surgery may still be an option. Median life expectancy at stage 3 is 17.9 months.

Cancer has spread extensively in the area where it developed. Chemotherapy and immunotherapy control symptoms and prolong survival. Median life expectancy at stage 4 is 14.9 months or less.

Mesothelioma is a rare cancer. It represents only 0.3 percent of all cancer diagnoses. Most doctors and oncologists have never encountered it.

A 2009 study published in the Journal of General Internal Medicine states that cancer care requires the technical knowledge and skills of specialty physicians such as medical oncologists, surgeons and radiation oncologists.

These are factors that impact a mesothelioma patients survival. Thats why finding a mesothelioma specialist is so important.

Finding a mesothelioma specialty center with experienced mesothelioma doctors is crucial to survival.

Brigham and Women's Hospital

Dr. Abraham Lebenthal is a respected thoracic surgeon who treats pleural mesothelioma patients at Brigham & Womens Hospital and Boston VA Hospital. Lebenthal worked alongside Dr. David Sugarbaker at Brigham and teaches at Harvard Medical School.

UCLA Jonsson Comprehensive Cancer Center

Dr. Robert B. Cameron developed a lung-sparing surgery for pleural mesothelioma that not only extends survival, but offers greater quality of life by preserving the lung. Camerons surgery has a lower risk of complications and studies report longer survival times.

H. Lee Moffitt Cancer Center

Dr. Jacques Fontaine is the Director of the Mesothelioma Research and Treatment Center at Moffitt Cancer Center in Tampa, Florida. He specializes in minimally invasive thoracic surgery including robotic surgery. Fontaine became a pleural mesothelioma specialist at Brigham & Womens Hospitals International Mesothelioma Program.

Washington Cancer Center

Dr. Paul Sugarbaker is the countrys leading expert on peritoneal mesothelioma. He developed the widely renowned cytoreductive surgery and heated chemotherapy technique that changed the landscape of peritoneal cancer treatment. Many people with peritoneal mesothelioma are alive today because of Sugarbakers innovations.

Ridley-Tree Cancer Center

Dr. W. Charles Conway is an expert in peritoneal mesothelioma and the Director of Surgical Oncology at Ridley-Tree Cancer Center in Santa Barbara, California. He specializes in minimally invasive robotic surgery and heated chemotherapy for peritoneal mesothelioma.

UPMC Hillman Cancer Center

Dr. J.F. Pingpank Jr. is a peritoneal mesothelioma expert who advocates for regional therapy. The approach applies treatment locally around the cancer to limit damage to the rest of the body. Pingpank specializes in cytoreductive surgery and heated chemotherapy.

We can help you or a loved one find a doctor who specializes in mesothelioma.

Mesothelioma treatment helps patients live longer lives. But not every patient is eligible for each type of mesothelioma treatment.

The most common treatments for mesothelioma include:

More than 70 percent of mesothelioma patients undergo chemotherapy

Clinical trials offer mesothelioma patients access to experimental therapies. They also provide scientific and medical information for researches to develop new treatments. Patients in clinical trials also receive excellent medical care.

Herbal medicines, mind-body therapies, holistic healing and other complementary therapies may benefit patients.

Thank you for the doctor referral info. We met with the doctor and came away with what seemed like a weight lifted.

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Many companies that produced, distributed or used asbestos products knew it was deadly. But they neglected to warn their employees. Filing a lawsuit can help mesothelioma patients cover lost wages, medical expenses and other costs.

$180,000 is the median value for mesothelioma claims, according to a 2010 report from the RAND Corporation, a nonprofit institution that conducts research and analysis on asbestos bankruptcy trusts.

A person with mesothelioma can file a personal injury lawsuit. Mesothelioma lawyers file these against companies responsible for their clients asbestos exposure. Families can file wrongful death claims when a loved one dies of mesothelioma.

Qualified mesothelioma attorneys can help you decide when to file a lawsuit. They can also guide you through the process. Time is of the essence because statute of limitations may expire. A mesothelioma lawyer will review your case so you receive the highest compensation.

Learn How to Hire a Qualified Mesothelioma Lawyer

Need help with treatment expenses? Find out if you qualify for financial assistance.

Support is available for mesothelioma patients, survivors and loved ones in many forms.

The Mesothelioma Centers monthly online support group meets every second Wednesday. Licensed mental health counselor Dana Nolan runs the support group. Patients and survivors can share their experiences with others on a similar cancer journey.

The first signs of mesothelioma include shortness of breath, cough and chest pain. Other initial symptoms include wheezing, weight loss and fatigue.

While there is no cure for any stage or type of mesothelioma, some early-stage patients have gone into remission for years after treatment. Remission means the cancer has stopped growing and spreading. Patients diagnosed early enough to qualify for surgery have the best chance of achieving remission.

Unfortunately, a number of stage 4 mesothelioma cases do not produce symptoms that clearly indicate a diagnosis of mesothelioma. The symptoms of mesothelioma lead most general practitioners to a diagnosis of pneumonia or another pulmonary condition. In most cases, mesothelioma is diagnosed in stage 4 at a hospital or cancer center by an oncologist and not by general practitioner.

Registered Nurse and Patient Advocate

Karen Selby joined Asbestos.com in 2009. She is a registered nurse with a background in oncology and thoracic surgery and was the regional director of a tissue bank before becoming a Patient Advocate at The Mesothelioma Center. Karen has assisted surgeons with thoracic surgeries such as lung resections, lung transplants, pneumonectomies, pleurectomies and wedge resections. She is also a member of the Academy of Oncology Nurse & Patient Navigators.

13 Cited Article Sources

Last Modified April 16, 2019

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Mesothelioma: What Is Malignant Mesothelioma Cancer?

Malignant Mesothelioma | Causes, Symptoms, Prognosis

Written By Tonya Nelson

Tonya Nelson is an experienced writer and editor, who has published on a wide variety of topics, particularly in the health field. Her bachelors degree in magazine journalism from the S.I. Newhouse School of Public Communications at Syracuse University sparked her curiosity for writing stories about environmental and medical issues. As the Managing Editor, Tonya oversees the content development process, ensuring every article and informational page published adheres to MAA Centers editorial guidelines.

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Malignant Mesothelioma | Causes, Symptoms, Prognosis

Mesothelioma.com | Information for Patients and Families

At Mesothelioma.com, our mission is to educate patients, their loved ones and the general public about this rare cancer and the toxin that causes it, asbestos. We strive to help those impacted by mesothelioma get the medical information, resources and legal connections they need at every step of their cancer journey.

For over 20 years, Mesothelioma.com has provided free medical and legal resources to mesothelioma patients and their families during their time of need. Our team consists of medical experts, legal experts, mesothelioma survivors, award-winning journalists and researchers to ensure the most helpful, accurate and recent information about mesothelioma, asbestos and asbestos litigation.

Mesothelioma.com is focused on providing the best, most up-to-date mesothelioma and asbestos information based on input from experts in the field, medical journals, government sites and trustworthy news sources.

Get detailed information about the disease, including symptoms, diagnosis, stages, treatment options, life expectancy and more.

Learn more about what factors impact your life expectancy, like type and stage of mesothelioma, as well as how some patients achieved long-term survival.

Browse our extensive database of mesothelioma doctors and cancer centers and get details on conventional treatments, emerging treatments and clinical trials that could help extend survival.

Find information about asbestos, the only definitive cause of mesothelioma, including where it can be found in homes, buildings and products and occupations most at risk of exposure.

Since asbestos was used heavily across all military branches, veterans are among the most at risk for mesothelioma and account for about 30% of all diagnoses today. Learn where asbestos was used, veteran treatments centers and how to file a VA claim.

Because asbestos companies acted with neglect, mesothelioma victims and their families have legal options. Learn about your rights, including types of claims and financial assistance available, and get help connecting with law firms with experience in asbestos litigation.

Heather Von St. James was diagnosed with pleural mesothelioma at 36 years old, just a few months after giving birth to her daughter. Without treatment, doctors told her she would have just 15 months to live. Heather and her family decided to pursue a new, aggressive treatment in Boston, and she is now a 13-year survivor. Today, Heather dedicates her life to advocating for patients and an asbestos ban. Connect with Heather.

Researchers have found that recurrent rates for mesothelioma can vary widely, with some studies finding recurrence rates after treatment ranging from 10 72%. Even patients diagnosed in the earlie...

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A California jury reached a $29 million verdict against Johnson & Johnson and Cyprus Mines Corporation, a talc supplier. The jury concluded that the responsible companies must pay Teresa Leavit...

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Mesothelioma: Free Book on Symptoms, Treatments, Support …

If you or someone you know has mesothelioma, order this free book to get practical answers about treatment options, support, legal options and more.

100 Questions & Answers About Mesothelioma is devoted to providing treatment information for those diagnosed with this disease. This book offers help - whether youre a newly diagnosed mesothelioma patient, a survivor, a friend or a relative. It is written from a medical perspective and gives you authoritative, practical answers to your questions about treatment options, post-treatment quality of life, sources of support, legal options and much more. Click here to learn more about this informational book.

Get your free, no obligation, copy of this book by filling out the contact form above or call us at 800.300.2919and the book will be rushed to you.

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Mesothelioma | Symptoms, Causes, and Prognosis Explained

Almost all of the approximately 3,000 cases of mesothelioma diagnosed every year were triggered by asbestos exposure. Most of that exposure occurred in the workplace. Employees exposed and put at risk of asbestos-related diseases never knew about the dangers until it was too late.

Many companies used this mineral until the government began regulating asbestos-containing materials in the 1970s. Workers who were more likely to be exposed include industrial workers, sailors and shipyard workers, construction laborers and skilled tradesmen, and miners, among many others.

Exposure to asbestos is now decreasing and minimal, but not all the damage has been done. People are still getting diagnosed with mesothelioma now because of the cancer's long latency period. Decades can pass between exposure and symptoms that lead to a diagnosis.

Researchers have made great improvements in diagnosing and treating mesothelioma. They are helping people live longer, but mesothelioma is still an aggressive and deadly type of cancer. There is no cure for mesothelioma.

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Mesothelioma | Symptoms, Causes, and Prognosis Explained

Mesothelioma – Wikipedia

Cancer associated with asbestos

Mesothelioma is a type of cancer that develops from the thin layer of tissue that covers many of the internal organs (known as the mesothelium).[9] The most common area affected is the lining of the lungs and chest wall.[1][3] Less commonly the lining of the abdomen and rarely the sac surrounding the heart,[10] or the sac surrounding the testis may be affected.[1][11] Signs and symptoms of mesothelioma may include shortness of breath due to fluid around the lung, a swollen abdomen, chest wall pain, cough, feeling tired, and weight loss.[1] These symptoms typically come on slowly.[2]

More than 80% of mesothelioma cases are caused by exposure to asbestos.[3] The greater the exposure the greater the risk.[3] As of 2013, about 125 million people worldwide have been exposed to asbestos at work.[12] High rates of disease occur in people who mine asbestos, produce products from asbestos, work with asbestos products, live with asbestos workers, or work in buildings containing asbestos.[3] Asbestos exposure and the onset of cancer are generally separated by about 40 years.[3] Washing the clothing of someone who worked with asbestos also increases the risk.[12] Other risk factors include genetics and infection with the simian virus 40.[3] The diagnosis may be suspected based on chest X-ray and CT scan findings, and is confirmed by either examining fluid produced by the cancer or by a tissue biopsy of the cancer.[2]

Prevention centers around reducing exposure to asbestos.[4] Treatment often includes surgery, radiation therapy, and chemotherapy.[5] A procedure known as pleurodesis, which involves using substances such as talc to scar together the pleura, may be used to prevent more fluid from building up around the lungs.[5] Chemotherapy often includes the medications cisplatin and pemetrexed.[2] The percentage of people that survive five years following diagnosis is on average 8% in the United States.[6]

In 2015, about 60,800 people had mesothelioma, and 32,000 died from the disease.[7][8] Rates of mesothelioma vary in different areas of the world.[3] Rates are higher in Australia, the United Kingdom, and lower in Japan.[3] It occurs in about 3,000 people per year in the United States.[13] It occurs more often in males than females.[3] Rates of disease have increased since the 1950s.[3] Diagnosis typically occurs after the age of 65 and most deaths occur around 70 years old.[3] The disease was rare before the commercial use of asbestos.[3]

Symptoms or signs of mesothelioma may not appear until 20 to 50 years (or more) after exposure to asbestos. Shortness of breath, cough, and pain in the chest due to an accumulation of fluid in the pleural space (pleural effusion) are often symptoms of pleural mesothelioma.[14]

Mesothelioma that affects the pleura can cause these signs and symptoms:[14]

In severe cases, the person may have many tumor masses. The individual may develop a pneumothorax, or collapse of the lung. The disease may metastasize, or spread to other parts of the body.

The most common symptoms of peritoneal mesothelioma are abdominal swelling and pain due to ascites (a buildup of fluid in the abdominal cavity). Other features may include weight loss, fever, night sweats, poor appetite, vomiting, constipation, and umbilical hernia.[15] If the cancer has spread beyond the mesothelium to other parts of the body, symptoms may include pain, trouble swallowing, or swelling of the neck or face.[citation needed]These symptoms may be caused by mesothelioma or by other, less serious conditions.

Tumors that affect the abdominal cavity often do not cause symptoms until they are at a late stage. Symptoms include:[citation needed]

Pericardial mesothelioma is not well characterized, but observed cases have included cardiac symptoms, specifically constrictive pericarditis, heart failure, pulmonary embolism, and cardiac tamponade. They have also included nonspecific symptoms, including substernal chest pain, orthopnea (shortness of breath when lying flat), and cough. These symptoms are caused by the tumor encasing or infiltrating the heart.[10]

In severe cases of the disease, the following signs and symptoms may be present:[citation needed]

If a mesothelioma forms metastases, these most commonly involve the liver, adrenal gland, kidney, or other lung.[16]

Working with asbestos is the most common risk factor for mesothelioma.[17] However, mesothelioma has been reported in some individuals without any known exposure to asbestos. Tentative evidence also raises concern about carbon-fibre nanotubes.[18][19]

The incidence of mesothelioma has been found to be higher in populations living near naturally occurring asbestos. People can be exposed to naturally occurring asbestos in areas where mining or road construction is occurring, or when the asbestos-containing rock is naturally weathered. Another common route of exposure is through asbestos-containing soil, which is used to whitewash, plaster, and roof houses in Greece.[12] In central Cappadocia, Turkey, mesothelioma was causing 50% of all deaths in three small villagesTuzky, Karain, and Sarhdr. Initially, this was attributed to erionite. Environmental exposure to asbestos has caused mesothelioma in places other than Turkey, including Corsica, Greece, Cyprus, China, and California.[12][20][21] In the northern Greek mountain town of Metsovo, this exposure had resulted in mesothelioma incidence around 300 times more than expected in asbestos-free populations, and was associated with very frequent pleural calcification known as "Metsovo Lung".[22][23]

The documented presence of asbestos fibers in water supplies and food products has fostered concerns about the possible impact of long-term and, as yet, unknown exposure of the general population to these fibers.[citation needed]

Exposure to talc is also a risk factor for mesothelioma; exposure can affect those who live near talc mines, work in talc mines, or work in talc mills.[24]

In the United States, asbestos is considered the major cause of malignant mesothelioma[25] and has been considered "indisputably"[26] associated with the development of mesothelioma. Indeed, the relationship between asbestos and mesothelioma is so strong that many consider mesothelioma a signal or sentinel tumor.[27][28][29][30] A history of asbestos exposure exists in most cases.

Pericardial mesothelioma may not be associated with asbestos exposure.[10]

Asbestos was known in antiquity, but it was not mined and widely used commercially until the late 19th century. Its use greatly increased during World War II. Since the early 1940s, millions of American workers have been exposed to asbestos dust. Initially, the risks associated with asbestos exposure were not publicly known. However, an increased risk of developing mesothelioma was later found among naval personnel (e.g., Navy, Marine Corps, and Coast Guard), shipyard workers, people who work in asbestos mines and mills, producers of asbestos products, workers in the heating and construction industries, and other tradespeople. Today, the official position of the U.S. Occupational Safety and Health Administration (OSHA) and the U.S. EPA is that protections and "permissible exposure limits" required by U.S. regulations, while adequate to prevent most asbestos-related non-malignant disease, are not adequate to prevent or protect against asbestos-related cancers such as mesothelioma.[31] Likewise, the British Government's Health and Safety Executive (HSE) states formally that any threshold for exposure to asbestos must be at a very low level and it is widely agreed that if any such threshold does exist at all, then it cannot currently be quantified. For practical purposes, therefore, HSE assumes that no such "safe" threshold exists. Others have noted as well that there is no evidence of a threshold level below which there is no risk of mesothelioma.[32] There appears to be a linear, doseresponse relationship, with increasing dose producing increasing risk of disease.[33] Nevertheless, mesothelioma may be related to brief, low level or indirect exposures to asbestos.[26] The dose necessary for effect appears to be lower for asbestos-induced mesothelioma than for pulmonary asbestosis or lung cancer.[26] Again, there is no known safe level of exposure to asbestos as it relates to increased risk of mesothelioma.

The time from first exposure to onset of the disease, is between 25 and 70 years.[34] It is virtually never less than fifteen years and peaks at 3040 years.[26][35] The duration of exposure to asbestos causing mesothelioma can be short. For example, cases of mesothelioma have been documented with only 13 months of exposure.[36][37]

Exposure to asbestos fibers has been recognized as an occupational health hazard since the early 20th century. Numerous epidemiological studies have associated occupational exposure to asbestos with the development of pleural plaques, diffuse pleural thickening, asbestosis, carcinoma of the lung and larynx, gastrointestinal tumors, and diffuse malignant mesothelioma of the pleura and peritoneum. Asbestos has been widely used in many industrial products, including cement, brake linings, gaskets, roof shingles, flooring products, textiles, and insulation.[38]

Commercial asbestos mining at Wittenoom, Western Australia, took place from 1937 to 1966. The first case of mesothelioma in the town occurred in 1960. The second case was in 1969, and new cases began to appear more frequently thereafter. The lag time between initial exposure to asbestos and the development of mesothelioma varied from 12 years 9 months up to 58 years.[39] A cohort study of miners employed at the mine reported that 85 deaths attributable to mesothelioma had occurred by 1985. By 1994, 539 reported deaths due to mesothelioma had been reported in Western Australia.[citation needed]

Occupational exposure to asbestos in the United States mainly occurs when people are maintaining buildings that already have asbestos. Approximately 1.3 million US workers are exposed to asbestos annually; in 2002, an estimated 44,000 miners were potentially exposed to asbestos.[24]

Family members and others living with asbestos workers have an increased risk of developing mesothelioma, and possibly other asbestos-related diseases.[11][40][41] This risk may be the result of exposure to asbestos dust brought home on the clothing and hair of asbestos workers via washing a worker's clothes or coming into contact with asbestos-contaminated work clothing.[12][24] To reduce the chance of exposing family members to asbestos fibres, asbestos workers are usually required to shower and change their clothing before leaving the workplace.[citation needed]

Many building materials used in both public and domestic premises prior to the banning of asbestos may contain asbestos. Those performing renovation works or DIY activities may expose themselves to asbestos dust. In the UK, use of chrysotile asbestos was banned at the end of 1999. Brown and blue asbestos were banned in the UK around 1985. Buildings built or renovated prior to these dates may contain asbestos materials.[citation needed]

In a recent research carried on white American population in 2012, it was found that people with a germline mutation in their BAP1 gene are at higher risk of developing mesothelioma and uveal melanoma.[42]

Erionite is a zeolite mineral with similar properties to asbestos and is known to cause mesothelioma.[11] Detailed epidemiological investigation has shown that erionite causes mesothelioma mostly in families with a genetic predisposition.[12][20][21] Erionite is found in deposits in the Western United States, where it is used in gravel for road surfacing, and in Turkey, where it is used to construct homes. In Turkey, the United States, and Mexico, erionite has been associated with mesothelioma and has thus been designated a "known human carcinogen" by the US National Toxicology Program.[21]

In rare cases, mesothelioma has also been associated with irradiation of the chest or abdomen, intrapleural thorium dioxide (thorotrast) as a contrast medium, and inhalation of other fibrous silicates, such as erionite or talc.[11][24] Some studies suggest that simian virus 40 (SV40) may act as a cofactor in the development of mesothelioma.[24] This has been confirmed in animal studies,[43][44] but studies in humans are inconclusive.[43][45][46]

The mesothelium consists of a single layer of flattened to cuboidal cells forming the epithelial lining of the serous cavities of the body including the peritoneal, pericardial and pleural cavities. Deposition of asbestos fibers in the parenchyma of the lung may result in the penetration of the visceral pleura from where the fiber can then be carried to the pleural surface, thus leading to the development of malignant mesothelial plaques. The processes leading to the development of peritoneal mesothelioma remain unresolved, although it has been proposed that asbestos fibers from the lung are transported to the abdomen and associated organs via the lymphatic system. Additionally, asbestos fibers may be deposited in the gut after ingestion of sputum contaminated with asbestos fibers.[citation needed]

Pleural contamination with asbestos or other mineral fibers has been shown to cause cancer. Long thin asbestos fibers (blue asbestos, amphibole fibers) are more potent carcinogens than "feathery fibers" (chrysotile or white asbestos fibers).[26] However, there is now evidence that smaller particles may be more dangerous than the larger fibers. They remain suspended in the air where they can be inhaled, and may penetrate more easily and deeper into the lungs. "We probably will find out a lot more about the health aspects of asbestos from [the World Trade Center attack], unfortunately," said Dr. Alan Fein, chief of pulmonary and critical-care medicine at North Shore-Long Island Jewish Health System.[47]

Mesothelioma development in rats has been demonstrated following intra-pleural inoculation of phosphorylated chrysotile fibers. It has been suggested that in humans, transport of fibers to the pleura is critical to the pathogenesis of mesothelioma. This is supported by the observed recruitment of significant numbers of macrophages and other cells of the immune system to localized lesions of accumulated asbestos fibers in the pleural and peritoneal cavities of rats. These lesions continued to attract and accumulate macrophages as the disease progressed, and cellular changes within the lesion culminated in a morphologically malignant tumor.[citation needed]

Experimental evidence suggests that asbestos acts as a complete carcinogen with the development of mesothelioma occurring in sequential stages of initiation and promotion. The molecular mechanisms underlying the malignant transformation of normal mesothelial cells by asbestos fibers remain unclear despite the demonstration of its oncogenic capabilities (see next-but-one paragraph). However, complete in vitro transformation of normal human mesothelial cells to a malignant phenotype following exposure to asbestos fibers has not yet been achieved. In general, asbestos fibers are thought to act through direct physical interactions with the cells of the mesothelium in conjunction with indirect effects following interaction with inflammatory cells such as macrophages.[citation needed]

Analysis of the interactions between asbestos fibers and DNA has shown that phagocytosed fibers are able to make contact with chromosomes, often adhering to the chromatin fibers or becoming entangled within the chromosome. This contact between the asbestos fiber and the chromosomes or structural proteins of the spindle apparatus can induce complex abnormalities. The most common abnormality is monosomy of chromosome 22. Other frequent abnormalities include structural rearrangement of 1p, 3p, 9p and 6q chromosome arms.[citation needed]

Common gene abnormalities in mesothelioma cell lines include deletion of the tumor suppressor genes:[citation needed]

Asbestos has also been shown to mediate the entry of foreign DNA into target cells. Incorporation of this foreign DNA may lead to mutations and oncogenesis by several possible mechanisms:

Several genes are commonly mutated in mesothelioma, and may be prognostic factors. These include epidermal growth factor receptor (EGFR) and C-Met, receptor tyrosine kinases which are overexpressed in many mesotheliomas. Some association has been found with EGFR and epithelioid histology but no clear association has been found between EGFR overexpression and overall survival. Expression of AXL receptor tyrosine kinase is a negative prognostic factor. Expression of PDGFRB is a positive prognostic factor.[49] In general, mesothelioma is characterized by loss of function in tumor suppressor genes, rather than by an overexpression or gain of function in oncogenes.[50]

As an environmentally triggered malignancy, mesothelioma tumors have been found to be polyclonal in origin, by performing a X-inactivation based assay on epitheloid and biphasic tumors obtained from female patients.[51] These results suggest that an environmental factor, most likely asbestos exposure, may damage and transform a group of cells in the tissue, resulting in a population of tumor cells that are, albeit only slightly, genetically different.[52]

Asbestos fibers have been shown to alter the function and secretory properties of macrophages, ultimately creating conditions which favour the development of mesothelioma. Following asbestos phagocytosis, macrophages generate increased amounts of hydroxyl radicals, which are normal by-products of cellular anaerobic metabolism. However, these free radicals are also known clastogenic (chromosome-breaking) and membrane-active agents thought to promote asbestos carcinogenicity. These oxidants can participate in the oncogenic process by directly and indirectly interacting with DNA, modifying membrane-associated cellular events, including oncogene activation and perturbation of cellular antioxidant defences.[citation needed]

Asbestos also may possess immunosuppressive properties. For example, chrysotile fibres have been shown to depress the in vitro proliferation of phytohemagglutinin-stimulated peripheral blood lymphocytes, suppress natural killer cell lysis and significantly reduce lymphokine-activated killer cell viability and recovery. Furthermore, genetic alterations in asbestos-activated macrophages may result in the release of potent mesothelial cell mitogens such as platelet-derived growth factor (PDGF) and transforming growth factor- (TGF-) which in turn, may induce the chronic stimulation and proliferation of mesothelial cells after injury by asbestos fibres.[citation needed]

Diagnosis of mesothelioma can be suspected with imaging but is confirmed with biopsy. It must be clinically and histologically differentiated from other pleural and pulmonary malignancies, including reactive pleural disease, primary lung carcinoma, pleural metastases of other cancers, and other primary pleural cancers.[11]Primary pericardial mesothelioma is often diagnosed after it has metastasized to lymph nodes or the lungs.[10]

Diagnosing mesothelioma is often difficult because the symptoms are similar to those of a number of other conditions. Diagnosis begins with a review of the patient's medical history. A history of exposure to asbestos may increase clinical suspicion for mesothelioma. A physical examination is performed, followed by chest X-ray and often lung function tests. The X-ray may reveal pleural thickening commonly seen after asbestos exposure and increases suspicion of mesothelioma.[14] A CT (or CAT) scan or an MRI is usually performed. If a large amount of fluid is present, abnormal cells may be detected by cytopathology if this fluid is aspirated with a syringe.[10] For pleural fluid, this is done by thoracentesis or tube thoracostomy (chest tube); for ascites, with paracentesis or ascitic drain; and for pericardial effusion with pericardiocentesis. While absence of malignant cells on cytology does not completely exclude mesothelioma, it makes it much more unlikely, especially if an alternative diagnosis can be made (e.g., tuberculosis, heart failure).[citation needed] However, with primary pericardial mesothelioma, pericardial fluid may not contain malignant cells and a tissue biopsy is more useful in diagnosis.[10] Using conventional cytology diagnosis of malignant mesothelioma is difficult, but immunohistochemistry has greatly enhanced the accuracy of cytology.[citation needed]

Generally, a biopsy is needed to confirm a diagnosis of malignant mesothelioma. A doctor removes a sample of tissue for examination under a microscope by a pathologist. A biopsy may be done in different ways, depending on where the abnormal area is located. If the cancer is in the chest, the doctor may perform a thoracoscopy. In this procedure, the doctor makes a small cut through the chest wall and puts a thin, lighted tube called a thoracoscope into the chest between two ribs. Thoracoscopy allows the doctor to look inside the chest and obtain tissue samples. Alternatively, the chest surgeon might directly open the chest (thoracotomy). If the cancer is in the abdomen, the doctor may perform a laparoscopy. To obtain tissue for examination, the doctor makes a small incision in the abdomen and inserts a special instrument into the abdominal cavity. If these procedures do not yield enough tissue, an open surgical procedure may be necessary.[citation needed]

Immunohistochemical studies play an important role for the pathologist in differentiating malignant mesothelioma from neoplastic mimics, such as breast or lung cancer that has metastasized to the pleura. There are numerous tests and panels available, but no single test is perfect for distinguishing mesothelioma from carcinoma or even benign versus malignant. The positive markers indicate that mesothelioma is present; if other markers are positive it may indicate another type of cancer, such as breast or lung adenocarcinoma. Calretinin is a particularly important marker in distinguishing mesothelioma from metastatic breast or lung cancer.[11]

There are three main histological subtypes of malignant mesothelioma: epithelioid, sarcomatous, and biphasic. Epithelioid and biphasic mesothelioma make up approximately 75-95% of mesotheliomas and have been well characterized histologically, whereas sarcomatous mesothelioma has not been studied extensively. Most mesotheliomas express high levels of cytokeratin 5 regardless of subtype.[11]

Epithelioid mesothelioma is characterized by high levels of calretinin.[11]

Sarcomatous mesothelioma does not express high levels of calretinin.[11]

Other morphological subtypes have been described:

Staging of mesothelioma is based on the recommendation by the International Mesothelioma Interest Group.[53] TNM classification of the primary tumor, lymph node involvement, and distant metastasis is performed. Mesothelioma is staged IaIV (one-A to four) based on the TNM status.[53][54]

Mesothelioma can be prevented in most cases by preventing exposure to asbestos. The US National Institute for Occupational Safety and Health maintains a recommended exposure limit of 0.1 asbestos fiber per cubic centimeter.[24]

There is no universally agreed protocol for screening people who have been exposed to asbestos. Screening tests might diagnose mesothelioma earlier than conventional methods thus improving the survival prospects for patients. The serum osteopontin level might be useful in screening asbestos-exposed people for mesothelioma. The level of soluble mesothelin-related protein is elevated in the serum of about 75% of patients at diagnosis and it has been suggested that it may be useful for screening.[55] Doctors have begun testing the Mesomark assay which measures levels of soluble mesothelin-related proteins (SMRPs) released by mesothelioma cells.[56]

Mesothelioma is generally resistant to radiation and chemotherapy treatment. Long-term survival and cures are exceedingly rare.[11] Treatment of malignant mesothelioma at earlier stages has a better prognosis. Clinical behavior of the malignancy is affected by several factors including the continuous mesothelial surface of the pleural cavity which favors local metastasis via exfoliated cells, invasion to underlying tissue and other organs within the pleural cavity, and the extremely long latency period between asbestos exposure and development of the disease. The histological subtype and the patient's age and health status also help predict prognosis. The epithelioid histology responds better to treatment and has a survival advantage over sarcomatoid histology.[57]

Surgery, by itself, has proved disappointing. In one large series, the median survival with surgery (including extrapleural pneumonectomy) was only 11.7 months.[58] However, research indicates varied success when used in combination with radiation and chemotherapy (Duke, 2008), or with one of the latter. A pleurectomy/decortication is the most common surgery, in which the lining of the chest is removed. Less common is an extrapleural pneumonectomy (EPP), in which the lung, lining of the inside of the chest, the hemi-diaphragm and the pericardium are removed.[citation needed] In localized pericardial mesothelioma, pericardectomy can be curative; when the tumor has metastasized, pericardectomy is a palliative care option. The entire tumor is not often able to be removed.[10]

For patients with localized disease, and who can tolerate a radical surgery, radiation can be given post-operatively as a consolidative treatment. The entire hemithorax is treated with radiation therapy, often given simultaneously with chemotherapy. Delivering radiation and chemotherapy after a radical surgery has led to extended life expectancy in selected patient populations. It can also induce severe side-effects, including fatal pneumonitis.[59] As part of a curative approach to mesothelioma, radiotherapy is commonly applied to the sites of chest drain insertion, in order to prevent growth of the tumor along the track in the chest wall.[citation needed]

Although mesothelioma is generally resistant to curative treatment with radiotherapy alone, palliative treatment regimens are sometimes used to relieve symptoms arising from tumor growth, such as obstruction of a major blood vessel. Radiation therapy, when given alone with curative intent, has never been shown to improve survival from mesothelioma. The necessary radiation dose to treat mesothelioma that has not been surgically removed would be beyond human tolerance.[citation needed] Radiotherapy is of some use in pericardial mesothelioma.[10]

Chemotherapy is the only treatment for mesothelioma that has been proven to improve survival in randomised and controlled trials. The landmark study published in 2003 by Vogelzang and colleagues compared cisplatin chemotherapy alone with a combination of cisplatin and pemetrexed (brand name Alimta) chemotherapy in patients who had not received chemotherapy for malignant pleural mesothelioma previously and were not candidates for more aggressive "curative" surgery.[60] This trial was the first to report a survival advantage from chemotherapy in malignant pleural mesothelioma, showing a statistically significant improvement in median survival from 10 months in the patients treated with cisplatin alone to 13.3 months in the group of patients treated with cisplatin in the combination with pemetrexed and who also received supplementation with folate and vitamin B12. Vitamin supplementation was given to most patients in the trial and pemetrexed related side effects were significantly less in patients receiving pemetrexed when they also received daily oral folate 500mcg and intramuscular vitamin B12 1000mcg every 9 weeks compared with patients receiving pemetrexed without vitamin supplementation. The objective response rate increased from 20% in the cisplatin group to 46% in the combination pemetrexed group. Some side effects such as nausea and vomiting, stomatitis, and diarrhoea were more common in the combination pemetrexed group but only affected a minority of patients and overall the combination of pemetrexed and cisplatin was well tolerated when patients received vitamin supplementation; both quality of life and lung function tests improved in the combination pemetrexed group. In February 2004, the United States Food and Drug Administration approved pemetrexed for treatment of malignant pleural mesothelioma. However, there are still unanswered questions about the optimal use of chemotherapy, including when to start treatment, and the optimal number of cycles to give.[citation needed] Cisplatin and pemetrexed together give patients a median survival of 12.1 months.[11]

Cisplatin in combination with raltitrexed has shown an improvement in survival similar to that reported for pemetrexed in combination with cisplatin, but raltitrexed is no longer commercially available for this indication. For patients unable to tolerate pemetrexed, cisplatin in combination with gemcitabine or vinorelbine is an alternative, or vinorelbine on its own, although a survival benefit has not been shown for these drugs. For patients in whom cisplatin cannot be used, carboplatin can be substituted but non-randomised data have shown lower response rates and high rates of haematological toxicity for carboplatin-based combinations, albeit with similar survival figures to patients receiving cisplatin.[61]

In January 2009, the United States FDA approved using conventional therapies such as surgery in combination with radiation and or chemotherapy on stage I or II Mesothelioma after research conducted by a nationwide study by Duke University concluded an almost 50 point increase in remission rates.[citation needed]

In pericardial mesothelioma, chemotherapy - typically adriamycin and/or cisplatin - is primarily used to shrink the tumor and is not curative.[10]

Treatment regimens involving immunotherapy have yielded variable results. For example, intrapleural inoculation of Bacillus Calmette-Gurin (BCG) in an attempt to boost the immune response, was found to be of no benefit to the patient (while it may benefit patients with bladder cancer). Mesothelioma cells proved susceptible to in vitro lysis by LAK cells following activation by interleukin-2 (IL-2), but patients undergoing this particular therapy experienced major side effects. Indeed, this trial was suspended in view of the unacceptably high levels of IL-2 toxicity and the severity of side effects such as fever and cachexia. Nonetheless, other trials involving interferon alpha have proved more encouraging with 20% of patients experiencing a greater than 50% reduction in tumor mass combined with minimal side effects.[citation needed]

This technique is used in conjunction with surgery,[62] including in patients with malignant pleural mesothelioma.[63] The surgeon removes as much of the tumor as possible followed by the direct administration of a chemotherapy agent, heated to between 40 and 48C, in the abdomen. The fluid is perfused for 60 to 120 minutes and then drained. High concentrations of selected drugs are then administered into the abdominal and pelvic surfaces. Heating the chemotherapy treatment increases the penetration of the drugs into tissues. Also, heating itself damages the malignant cells more than the normal cells.[citation needed]

All of the standard approaches to treating solid tumorsradiation, chemotherapy, and surgeryhave been investigated in patients with malignant pleural mesothelioma. Although surgery, by itself, is not very effective, surgery combined with adjuvant chemotherapy and radiation (trimodality therapy) has produced significant survival extension (314 years) among patients with favorable prognostic factors.[64] However, other large series of examining multimodality treatment have only demonstrated modest improvement in survival (median survival 14.5 months and only 29.6% surviving 2 years).[58] Reducing the bulk of the tumor with cytoreductive surgery is key to extending survival. Two surgeries have been developed: extrapleural pneumonectomy and pleurectomy/decortication. The indications for performing these operations are unique. The choice of operation namely depends on the size of the patient's tumor. This is an important consideration because tumor volume has been identified as a prognostic factor in mesothelioma.[65] Pleurectomy/decortication spares the underlying lung and is performed in patients with early stage disease when the intention is to remove all gross visible tumor (macroscopic complete resection), not simply palliation.[66] Extrapleural pneumonectomy is a more extensive operation that involves resection of the parietal and visceral pleurae, underlying lung, ipsilateral (same side) diaphragm, and ipsilateral pericardium. This operation is indicated for a subset of patients with more advanced tumors, who can tolerate a pneumonectomy.[67]

Mesothelioma often has a poor prognosis. Typical survival despite surgery is between 12 and 21 months depending on the stage of disease at diagnosis with about 7.5% of people surviving for 5 years.[68]

Women, young people, people with low-stage cancers, and people with epithelioid cancers have better prognoses.[11] Negative prognostic factors include sarcomatoid or biphasic histology, high platelet counts (above 400,000), age over 50 years, white blood cell counts above 15.5, low glucose levels in the pleural fluid, low albumin levels, and high fibrinogen levels. Several markers are under investigation as prognostic factors, including nuclear grade, and serum c-reactive protein. Long-term survival is rare.[49]

Pericardial mesothelioma has a 10-month median survival time.[10]

In peritoneal mesothelioma, high expression of WT-1 protein indicates a worse prognosis.[11]

Although reported incidence rates have increased in the past 20 years, mesothelioma is still a relatively rare cancer. The incidence rate varies from one country to another, from a low rate of less than 1 per 1,000,000 in Tunisia and Morocco, to the highest rate in Britain, Australia and Belgium: 30 per 1,000,000 per year.[69] For comparison, populations with high levels of smoking can have a lung cancer incidence of over 1,000 per 1,000,000. Incidence of malignant mesothelioma currently ranges from about 7 to 40 per 1,000,000 in industrialized Western nations, depending on the amount of asbestos exposure of the populations during the past several decades.[70] Worldwide incidence is estimated at 1-6 per 1,000,000.[11] Incidence of mesothelioma lags behind that of asbestosis due to the longer time it takes to develop; due to the cessation of asbestos use in developed countries, mesothelioma incidence is expected to decrease.[24] Incidence is expected to continue increasing in developing countries due to continuing use of asbestos.[11] Mesothelioma occurs more often in men than in women and risk increases with age, but this disease can appear in either men or women at any age. Approximately one fifth to one third of all mesotheliomas are peritoneal.[citation needed] Less than 5% of mesotheliomas are pericardial. The prevalence of pericardial mesothelioma is less than 0.002%; it is more common in men than women. It typically occurs in a person's 50s-70s.[10][71]

Between 1940 and 1979, approximately 27.5 million people were occupationally exposed to asbestos in the United States.[72] Between 1973 and 1984, the incidence of pleural mesothelioma among Caucasian males increased 300%. From 1980 to the late 1990s, the death rate from mesothelioma in the USA increased from 2,000 per year to 3,000, with men four times more likely to acquire it than women.[citation needed] More than 80% of mesotheliomas are caused by asbestos exposure.[11]

The incidence of peritoneal mesothelioma is 0.53.0 per million per year in men, and 0.22.0 per million per year in women.[73]

Mesothelioma accounts for less than 1% of all cancers diagnosed in the UK, (around 2,600 people were diagnosed with the disease in 2011), and it is the seventeenth most common cause of cancer death (around 2,400 people died in 2012).[74]

The connection between asbestos exposure and mesothelioma was discovered in the 1970s. In the United States, asbestos manufacture stopped in 2002. Asbestos exposure thus shifted from workers in asbestos textile mills, friction product manufacturing, cement pipe fabrication, and insulation manufacture and installation to maintenance workers in asbestos-containing buildings.[24]

Mesothelioma, though rare, has had a number of notable patients:

Although life expectancy with this disease is typically limited, there are notable survivors. In July 1982, Stephen Jay Gould, a well-regarded paleontologist, was diagnosed with peritoneal mesothelioma. After his diagnosis, Gould wrote "The Median Isn't the Message",[81] in which he argued that statistics such as median survival are useful abstractions, not destiny. Gould lived for another 20 years, eventually succumbing to cancer not linked to his mesothelioma.

Some people who were exposed to asbestos have collected damages for an asbestos-related disease, including mesothelioma. Compensation via asbestos funds or class action lawsuits is an important issue in law practices regarding mesothelioma.[citation needed]

The first lawsuits against asbestos manufacturers were in 1929. Since then, many lawsuits have been filed against asbestos manufacturers and employers, for neglecting to implement safety measures after the links between asbestos, asbestosis, and mesothelioma became known (some reports seem to place this as early as 1898). The liability resulting from the sheer number of lawsuits and people affected has reached billions of dollars.[82] The amounts and method of allocating compensation have been the source of many court cases, reaching up to the United States Supreme Court, and government attempts at resolution of existing and future cases. However, to date, the US Congress has not stepped in and there are no federal laws governing asbestos compensation.[83]In 2013, the "Furthering Asbestos Claim Transparency (FACT) Act of 2013" passed the US House of representatives and was sent to the US Senate, where it was referred to the Senate Judiciary Committee.[84] As the Senate did not vote on it before the end of the 113th Congress, it died in committee. It was revived in the 114th Congress, where it has not yet been brought before the House for a vote.[85]

The first lawsuit against asbestos manufacturers was brought in 1929. The parties settled that lawsuit, and as part of the agreement, the attorneys agreed not to pursue further cases. In 1960, an article published by Wagner et al. was seminal in establishing mesothelioma as a disease arising from exposure to asbestos.[86] The article referred to over 30 case studies of people who had suffered from mesothelioma in South Africa. Some exposures were transient and some were mine workers. Before the use of advanced microscopy techniques, malignant mesothelioma was often diagnosed as a variant form of lung cancer.[87] In 1962, McNulty reported the first diagnosed case of malignant mesothelioma in an Australian asbestos worker.[88] The worker had worked in the mill at the asbestos mine in Wittenoom from 1948 to 1950.[citation needed]

In the town of Wittenoom, asbestos-containing mine waste was used to cover schoolyards and playgrounds. In 1965, an article in the British Journal of Industrial Medicine established that people who lived in the neighbourhoods of asbestos factories and mines, but did not work in them, had contracted mesothelioma.[citation needed]

Despite proof that the dust associated with asbestos mining and milling causes asbestos-related disease, mining began at Wittenoom in 1943 and continued until 1966. In 1974, the first public warnings of the dangers of blue asbestos were published in a cover story called "Is this Killer in Your Home?" in Australia's Bulletin magazine. In 1978, the Western Australian Government decided to phase out the town of Wittenoom, following the publication of a Health Dept. booklet, "The Health Hazard at Wittenoom", containing the results of air sampling and an appraisal of worldwide medical information.[citation needed]

By 1979, the first writs for negligence related to Wittenoom were issued against CSR and its subsidiary ABA, and the Asbestos Diseases Society was formed to represent the Wittenoom victims.[citation needed]

In Leeds, England the Armley asbestos disaster involved several court cases against Turner & Newall where local residents who contracted mesothelioma demanded compensation because of the asbestos pollution from the company's factory. One notable case was that of June Hancock, who contracted the disease in 1993 and died in 1997.[89]

The WT-1 protein is overexpressed in mesothelioma and is being researched as a potential target for drugs.[11]

There are two high-confidence miRNAs that can potentially serve as biomarkers of asbestos exposure and malignant mesothelioma. Validation studies are needed to assess their relevance.[90]

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