Most malignant diseases of the pleura present with a unilateral pleural effusion or thickening. Malignant diseases include the very common secondary malignancy metastatic to the pleura, the less common lung cancer patient with pleural carcinomatosis, and the uncommon patient with primary malignant pleural mesothelioma (MPM). The low morbidity and accuracy of diagnostic thoracoscopy and pleural biopsy have dramatically increased our understanding and treatment of these diseases. This section of chapters provides important details and management of this group of primary malignant and secondary malignant diseases of the pleura.
Ironically, much of our insight has been gained by trying to understand the least common yet deadliest of this group of diseases: pleural mesothelioma. The current incidence of pleural mesothelioma within the United States is 2000 to 3000 cases per year as compared with esophageal and lung cancer, which are at least four and 50 times more common, respectively.1 Few physicians will treat more than a handful of cases of MPM over the course of their professional careers. Even fewer academic centers in North America and Europe have been able to acquire a collective experience large enough to develop new treatment protocols for this devastating disease. The Brigham and Women’s Hospital (BWH) and Dana-Farber Cancer Institute (DFCI) in Boston, Massachusetts, have gained a large experience treating MPM over the last 25 years.
The recognition of mesothelioma as a cancer and the development of treatment options are recent developments in the context of medical history. In 1950, Stout described malignant mesothelioma as a separate pathologic entity.2 Stout also described the three histologic subsets: epithelial, fibrosarcomatous, and mixed.
In 1960, Wagner et al.3 published the first mesothelioma case series, reporting on 33 patients from a South African asbestos mining town with known occupational and environmental crocidolite exposure. In the 1970s, a landmark study by Selikoff4 was published which established a firm link between asbestos exposure and mesothelioma. The investigators followed 17,800 asbestos insulation workers in the United States and Canada for a period of up to 50 years. They found that the incidence of mesothelioma within this group increased rapidly starting 20 to 25 years after the first exposure. Peak incidence occurred at 40 to 45 years after exposure. Seven percent of all deaths in this group of asbestos workers were due to mesothelioma, a shockingly high incidence for a rare cancer. Family members of asbestos workers also have a substantial increased risk, termed “bystander risk,” thought to be secondary to exposure to hair and clothes brought into the home.5
Early efforts at surgical and nonsurgical treatments were disappointing. Worn6 published one of the first series of patients undergoing extrapleural pneumonectomy (EPP) in 1974 reporting a 5-year survival rate of 10% and a median survival of 19 months. Butchart et al.7 published their initial experience with EPP for maximal surgical debulking of pleural mesothelioma in 1976. EPP had previously been used for tuberculous empyema, but was an operative technique that had always been associated with a high perioperative mortality. In Butchart’s series, EPP for MPM had a perioperative mortality rate of 31%, a 5-year survival of 3.5%, and a median survival of 10 months. Although operative mortality has now been reduced to less than 4%, EPP is a technically demanding operation, and details of the operative technique are included in Chapters 122 and 123.
Initial studies investigating adjuvant chemotherapy and radiation therapy repeatedly showed little to no activity against the disease. Median survival of patients enrolled in therapeutic trials varied from 3 to 17 months with the majority falling in the 6 to 10 month range.8,9 As the genetic and biochemical abnormalities of the malignant mesothelioma cell became understood, the chemotherapeutic options have dramatically improved.
New England has had a rich maritime military history. In August 1776, patriot soldiers from Marblehead and Salem, Massachusetts, rowed George Washington’s army to safety across Long Island Sound after the defeat on Brooklyn Heights. Three of the first six frigates built for the fledgling United States Navy were built in New England or New York. The large whaling and cod fishing fleets from New Bedford, Nantucket, and Gloucester were the major oil producers for over 200 years.
The pace of production of United States naval ships during World War II reached one ship per week in the large shipyards of New England and New York. Asbestos slurry was sprayed upon the bulkheads of the ships to insulate the compartments from the cold of the North Sea, as well as insulation against fire within individual sections of the ship. Although quickly and easily applied to the bulkheads, this asbestos slurry would flake and particles of asbestos dust would be suspended in the air once it had dried. Unaware of the long-term complications of this exposure, the shipyard workers did not wear protective clothing or masks. Many mesothelioma patients who served on these ships describe a cloud of white dust below decks whenever the large guns of the warship were fired.
A large proportion of the New England population came into contact with substantial quantities of asbestos by either working within the New England shipyards, or serving in the navy. Asbestos was also commonly used to insulate heaters within the home, exposing an even larger New England population.
The long latency period from exposure to development of the cancer has contributed to the high frequency of pleural mesothelioma in the greater Boston area during the past two decades. Prospective studies following people with known asbestos exposure have demonstrated a rapid rise in the incidence of malignant mesothelioma beginning at 20 years post exposure and a peak incidence of approximately 0.6% per year 40 to 45 years after exposure.
Asbestos continued to be used in manufacturing for many years. In the United States, it wasn’t until 1986 that the Toxic Substance Control Act addressed the health risks of asbestos giving the EPA broad authority to regulate the manufacture, use, distribution in commerce, and disposal of the carcinogenic substance.
When one considers the timing of these federal regulations, the latency of the disease, the geographical distribution of asbestos exposure, and the history of asbestos use, it is no coincidence that the BWH has become an epicenter of treatment for MPM.
