Mesothelioma

is a form of cancer that is almost always caused by previous exposure to asbestos In this disease, malignant cells develop in the mesothelium, a protective lining that covers most of the body's internal organs. Its most common site is the pleura (outer lining of the lungs and chest cavity), but it may also occur in the peritoneum (the lining of the abdominal cavity) or the pericardium (a sac that surrounds the heart). Most people who develop mesothelioma have worked on jobs where they inhaled asbestos particles, or have been exposed to asbestos dust and fibre in other ways, such as by washing the clothes of a family member who worked with asbestos, or by home renovation using asbestos cement products. There is no association between mesothelioma and smoking. Legal issues 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 link 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. The amounts and method of allocating compensation have been the source of many court cases, and government attempts at resolution of existing and future cases. 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. It was not until 1960 that an article published by Wagner et al in 1960 first officially established mesothelioma as a disease arising from exposure to crocidolite asbestos[8]. 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. In 1962 Dr McNulty reported the first diagnosed case of malignant mesothelioma in an Australian asbestos worker[9]. The worker had worked in the mill at the asbestos mine in Wittenoom from 1948 to 1950. 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. 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. It is difficult to understand why the mine and mill was allowed to initially open and operate without adequate risk control measures; and why nothing was done to force the owner (CSR) to clean them up, adopt safer work practices or close down their operations. 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. 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 Pathophysiology 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 fibres in the parenchyma of the lung may result in the penetration of the visceral pleura from where the fibre 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 fibres from the lung are transported to the abdomen and associated organs via the lymphatic system. Additionally, asbestos fibres may be deposited in the gut after ingestion of sputum contaminated with asbestos fibres. Pleural contamination with asbestos or other mineral fibres 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)[4]. However, there is now evidence that smaller particles may be more dangerous than the larger fibers.[1][2] 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. Dr. Fein has treated several patients for "World Trade Center syndrome" or respiratory ailments from brief exposures of only a day or two near the collapsed buildings.[3] Mesothelioma development in rats has been demonstrated following intra-pleural inoculation of phosphorylated chrysotile fibres. It has been suggested that in humans, transport of fibres 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 localised lesions of accumulated asbestos fibres 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 tumour. 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 fibres remain unclear despite the demonstration of its oncogenic capabilities. However, complete in vitro transformation of normal human mesothelial cells to malignant phenotype following exposure to asbestos fibres has not yet been achieved. In general, asbestos fibres 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. Analysis of the interactions between asbestos fibres and DNA has shown that phagocytosed fibres are able to make contact with chromosomes, often adhering to the chromatin fibres or becoming entangled within the chromosome. This contact between the asbestos fibre 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. Common gene abnormalities in mesothelioma cell lines include deletion of the tumor suppressor genes: Neurofibromatosis type 2 at 22q12 P16INK4A P14ARF 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: Inactivation of tumor suppressor genes Activation of oncogenes Activation of proto-oncogenes due to incorporation of foreign DNA containing a promoter region Activation of DNA repair enzymes, which may be prone to error Activation of telomerase Prevention of apoptosis Asbestos fibres 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 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. Asbestos may also 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 (LAK) 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-β (TGF-β) which in turn, may induce the chronic stimulation and proliferation of mesothelial cells after injury by asbestos fibres. Signs and symptoms Symptoms of mesothelioma may not appear until 20 to 50 years after exposure to asbestos. Shortness of breath, cough, and pain in the chest due to an accumulation of fluid in the pleural space are often symptoms of pleural mesothelioma. Symptoms of peritoneal mesothelioma include weight loss and cachexia, abdominal swelling and pain due to ascites (a buildup of fluid in the abdominal cavity). Other symptoms of peritoneal mesothelioma may include bowel obstruction, blood clotting abnormalities, anemia, and fever. 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. These symptoms may be caused by mesothelioma or by other, less serious conditions. Mesothelioma that affects the pleura can cause these signs and symptoms: chest wall pain pleural effusion, or fluid surrounding the lung shortness of breath wheezing, hoarseness, or cough 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. Tumors that affect the abdominal cavity often do not cause symptoms until they are at a late stage. Symptoms include: abdominal pain ascites, or an abnormal buildup of fluid in the abdomen a mass in the abdomen problems with bowel function weight loss In severe cases of the disease, the following signs and symptoms may be present: blood clots in the veins, which may cause thrombophlebitis disseminated intravascular coagulation, a disorder causing severe bleeding in many body organs jaundice, or yellowing of the eyes and skin low blood sugar level pleural effusion pulmonary emboli, or blood clots in the arteries of the lungs severe ascites A mesothelioma does not usually spread to the bone, brain, or adrenal glands. Pleural tumors are usually found only on one side of the lungs. Malignant Mesothelioma Symptoms Symptoms of malignant mesothelioma in the lung and chest cavity are as follows: Shortness of breath Cough Weight Loss Chest Pain Symptoms of malignant mesothelioma in the abdomen are as follows: Abdominal swelling and pain Weight Loss Wondering How You Could Have Gotten Mesothelioma Cancer? Several diseases are associated with exposure to asbestos. They include: malignant mesothelioma, asbestosis, pleural effusion, pleural plaques and thickening, and lung cancer. Prior to 1975 asbestos fibers were commonly used. You could have been exposed to asbestos while working at any number of different industries. Chief among the possibilities would be jobs at asbestos mining and milling plants, shipyards, fireproofing and heating, construction, automotive repair, insulation, pipefitting and boilermaking. If you did not work in one of these industries or another that used asbestos, it is also possible that you could have been exposed if someone in your household worked with asbestos and carried asbestos fibers home on his or her clothing, hair or body. You may also have been exposed indirectly by living near asbestos mines. Although it is true that most patients with malignant mesothelioma, lung cancer or other asbestos-related diseases likely had prolonged exposure to asbestos over a long period of time, it is also possible for one to develop one of these diseases from a brief exposure to asbestos. The odds of developing lung cancer from smoking also increases significantly from exposure to asbestos. Although most people with lung cancer are told that their lung cancer was caused from smoking, if you or someone you know has lung cancer and also worked in an environment that gave you exposure to asbestos, it is highly recommended that you contact an attorney that specializes in handling mesothelioma and lung cancer cases caused by exposure to asbestos. The justice system has been very generous in its rewards to people who suffer diseases caused by asbestos exposure Diagnosis 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. 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 cytology if this fluid is aspirated with a syringe. For pleural fluid this is done by a pleural tap or chest drain, in ascites with an paracentesis or ascitic drain and in a 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). If cytology is positive or a plaque is regarded as suspicious, a biopsy is needed to confirm a diagnosis of mesothelioma. A doctor removes a sample of tissue for examination under a microscope by a histopathologist. 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. If the cancer is in the abdomen, the doctor may perform a laparoscopy. To obtain tissue for examination, the doctor makes a small opening in the abdomen and inserts a special instrument into the abdominal cavity. If these procedures do not yield enough tissue, more extensive diagnostic surgery may be necessary. Mesothelioma Diagnosis Aided by Imaging and Sampling Because mesothelioma is a rare disease, it may be misdiagnosed by the everyday physician. Often, it is necessary to find a specialist who has treated numerous mesothelioma patients. A history of asbestos exposure will be an important factor in the physician’s diagnostic plan, which generally includes imaging tests, such as x–rays, CT, MRI, or PET scans and tissue and fluid sampling. X–Rays as Preliminary Step in Mesothelioma Diagnosis A chest x–ray may indicate irregular thickening of the pleura or the thin covering that protects and cushions the lungs. It may also show pleural calcifications (mineral deposits), lowering of the lung fissures (spaces between the lobes of the lungs) and accumulation of fluid in the lungs (pleural effusion) or in the abdomen (ascites). These may be ominous signs leading to a mesothelioma diagnosis. CT, MRI, and PET Scans for Mesothelioma Diagnosis and Tumor Detection A computed tomography or CT scan is useful in determining the location, size and extent of cancer such as mesothelioma. It is a special radiographic technique that uses a computer to combine multiple x–ray images into a two dimensional cross–sectional x–ray image. A machine rotates 180 degrees around the patient’s body, sending out a thin x–ray beam at numerous points. Crystals at the opposite points of the beam pick up and record the absorption rates of the varying thickness’ of tissue and bone. The computer turns the information into a detailed picture. The CT scan allows a radiologist to see distinct aspects of the lungs and pleura to better advantage than the x–ray. Magnetic resonance imaging (MRI) scans use magnetic fields, radio waves, and a computer to create images of selected areas of the body. MRI images tend to be quite clear and are superior to routine x–ray images. Positron emission tomography (PET) scans use cameras and tracers to form images that indicate biological changes and detect extremely small cancerous tumors. PET scans often provide even more information than CT or MRI scans. Mesothelioma Tissue and Fluid Samples A needle may be inserted into the chest cavity to remove fluid for sampling purposes. The same method is used to extract fluid samples from the abdomen or pericardium. Microscopic and chemical examination of the fluid can be essential to determine whether cancer cells are present. Tissue samples may be obtained through surgical techniques. In “thoracoscopy”, a thin telescopic instrument (thoracoscope) fitted with a lighting system is inserted through a puncture in the chest wall. The physician can see the tumor and sample it using a forceps–like tool. Special stains or electron microscopy can aid tissues analysis. The most common stains include acid–Schiff diastase, hyaluronic acid, mucicarmine, CEA, and Leu M1. These “immunohistochemical” procedures are useful to ensure an accurate mesothelioma diagnosis