The history of mesothelioma is a long, complex story filled with controversies that span hundreds of years of medical investigation. Before the disease was identified and categorized as a distinct type of cancer, past generations of medical and scientific experts grappled with understanding where it originated in the body and how it progressed once it struck.
Because it was so rare and such a mystery, this fatal cancer went misdiagnosed for years. A long history of studies culminated in a better — though still not complete — understanding of the cancer. Doctors now have answers to once elusive questions: What causes this fatal illness and who is at risk?
Today, doctors know that exposure to asbestos causes cancerous cells to develop in the mesothelial lining of the lungs, abdomen or heart. They know between 2,000 and 3,000 people get diagnosed with mesothelioma each year in the United States. And they know that treatment for the four types of mesothelioma and other asbestos-related conditions are only minimally effective. With numbers like that, doctors continue to try to raise awareness about mesothelioma.
According to medical literature, the earliest mention of a tumor in the lining of the lungs (pleura) was made in 1767 by Joseph Lieutaud, the founder of pathologic anatomy in France. In a publication detailing the study of some 3,000 autopsies he performed, Lieutaud mentioned two cases of “pleural tumors.”
In one, he found fleshy masses adherent to the pleura and the ribs of a deceased boy.
In 1819, René-Théophile-Hyacinthe Laennec, the French physician who invented the stethoscope, suggested that malignancy could arise from the pleura, based upon his understanding of the nature of pleural cells.
However, in 1843, Karl Freiherr von Rokitansky, professor of pathological anatomy at Vienna University challenged that notion, stating that pleural cancer was always secondary to a primary cancer elsewhere in the body.
Regardless of the lack of compelling evidence, this became the accepted theory of the medical establishment for many years. (Ironically, von Rokitansky later described primary tumors of the peritoneum, likely the first recorded cases of peritoneal mesothelioma.)
In 1943, H.W. Wedler was the first to report a connection between asbestosis and cancer of the pleura among German asbestos workers. Twenty percent of the workers had developed cancer, with lung cancer being more common than mesothelioma. Wedler’s study was well received in Germany, but the political climate at the time caused the rest of the world to ignore research coming from Nazi Germany.
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Over the next several decades, various theories about the nature of mesothelioma arose. By the end of the 19th century, experts still disagreed whether this form of cancer began in the lymphatic system and spread to the lungs and abdomen or whether it started from tumors elsewhere in the body.
Doctors also debated whether the cancerous tumors arose from the mesothelial lining of the pleura and peritoneum. The low number of patients hampered research, making it difficult to reach a consensus based on so little clinical data.
But by the early 1900s, the medical community began to finally accept that cancers could originate in the pleura without having spread from a primary cancer elsewhere in the body.
Mesothelioma is a rare form of cancer in which malignant cells form in the lining of the lungs (pleura), the lining of the abdominal cavity (peritoneum) or the lining around the heart (pericardium).
In 1909, J.G. Adami coined the term for these types of cancers: mesothelioma. Then in 1931, P. Klemperer and C.B. Rabin established a framework for diagnosing the disease and understanding its pathology.
It was during this time that doctors began to question its cause, and in 1935, London pathologist Steven Gloyne suggested a possible connection between the disease and occupational asbestos exposure.
In the following decades, the disease became the focus of closer studies, as thousands of workers all over the world died from exposure to the mineral's toxic dust. In 1970 alone, 602 Americans workers died of mesothelioma cancer, which remains latent in the body for 20 to 50 years.
Perhaps the most important study that documented the unmistakable connection between asbestos exposure and cancer was presented by medical researcher J.C. Wagner and physician Chris Sleggs. Sleggs was the medical superintendent of a chest and infectious disease hospital commissioned by the government of South Africa in 1948 in the country's northwest Cape Province, where crocidolite asbestos was mined.
Wagner had been hired by the government's Ministry of Mines to study occupational hazards associated with asbestos mining. During the course of his research, Sleggs found unusual pleural tumors in the bodies of asbestos workers.
In their paper published by the British Journal of Medicine in 1960, Sleggs and Wagner detailed 33 cases of mesothelioma they discovered, with all but one case having = a proven history of asbestos exposure. In eight cases, the exposure history was occupational. The rest of the patients lived near the mines for most of their lives.
Unfortunately, Wagner’s history with asbestos and mesothelioma became tarnished in the 1990s when court documents revealed he was on the payroll of defense attorneys working for the asbestos manufacturers.
Other studies followed, most notably the 1964 report of American physician, Dr. Irving J. Selikoff. He presented his findings at the “Biological Effects of Asbestos” conference, sponsored by the New York Academy of Science. For more than a year, Selikoff examined more than 1,000 workers from the Union Asbestos & Rubber Company plant in Patterson, New Jersey — workers whose jobs included producing asbestos insulation materials for the U.S. Navy.
Selikoff found that the mortality rate among these employees was 25 percent higher than would be expected statistically and that the deceased workers had died from a variety of diseases, including asbestosis, asbestos-related lung cancer and other types of lung, stomach, colon, rectal and colorectal cancers.
Another study by British physician, Molly Newhouse, found mesothelioma cases among people who lived near, but were not employed by, a London asbestos factory. By 1968, the British Medical Journal claimed asbestos was the direct cause of most cases (even though controversy still raged as to what types of asbestos were the most carcinogenic — a contentious argument that still echoes to this day).
But after many years of research, conjecture and controversy, most of the world's medical establishment had unequivocally accepted two important facts about mesothelioma:
Surgical treatment of mesothelioma began in the 1940s with the use of pneumonectomy and pleurectomy. In the 1960s, pleurectomy/decortication was introduced, a surgery that is still widely used today. The surgery was originally used on patients with trapped lung caused by tuberculous empyema.
In the 1970s, doctors experimented with another surgery called extrapleural pneumonectomy, which was also originally used to treat tuberculous empyema. The mortality rate for the surgery back then was as high as 31 percent, and today it’s around 4 percent in leading cancer centers.
A number of chemotherapy drugs were tried on mesothelioma from the 1970s through the 1990s, such as doxorubicin and cisplatin, with response rates between 20 percent and 40 percent. In 2003, the phase III trial of cisplatin and pemetrexed for mesothelioma reported the best response rate to date of 41.3 percent. After that study, cisplatin and pemetrexed became the most used chemotherapy drugs for mesothelioma.
Doctors began experimenting with radiation therapy for mesothelioma in the 1950s using radioactive gold, nitrogen mustard and X-rays. For decades it was believed that radiation therapy was too difficult to deliver to the pleura without harming other vital organs like the heart. A 2001 phase II clinical trial changed that perspective when it reported a low 13 percent local recurrence rate when radiation therapy was applied after EPP surgery. Advanced techniques are used today to reduce radiation exposure to vital organs, such as Intensity Modulate Radiation Therapy (IMRT).
Combining more than one therapy to increase effectiveness, known as multimodal therapy, has been used on mesothelioma since the cancer was first discovered. Numerous clinical trials have sought to find the ideal combination of therapies, but it appears different combinations may be ideal for different patients.
The first and only standalone research facility developed to focus on mesothelioma opened in Australia in 2009. The Asbestos Diseases Research Institute conducts research primarily on mesothelioma treatment, including looking for new ways to treat the cancer. The center also studies the diagnosis of mesothelioma and the psychological impact the cancer has on patients and families.
Currently, there is no standalone research facility in the U.S. that solely researches mesothelioma. Certain cancer centers in the U.S. feature programs that focus on the treatment of mesothelioma and participate in clinical trials, such as the International Mesothelioma Program at Brigham and Women’s Hospital in Boston.
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