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Mesothelioma symptoms tend to develop gradually, and earlier symptoms are often confused for illnesses that are more amenable to treatment. For example, the cough, difficulty breathing, and chest pain experienced in pleural mesothelioma is often seen in lung infections such as pneumonia. Typically, once symptoms are more pronounced the cancer is fairly advanced and treatment becomes less effective.

In advanced pleural mesothelioma, chest pain and pain under the ribcage may become more pronounced; back pain may also be present. Coughing may be present; blood may also be coughed up. Hoarseness and swelling of the face and arms may be seen. Patients may also experience muscle weakness and sensory loss. In advanced peritoneal mesothelioma, abdominal symptoms become more pronounced. These include a swelling or lump in the abdomen, abdominal distension due to a collection of fluid in the abdominal cavity, abdominal pain, constipation due to bowel obstruction, nausea and vomiting, and appetite loss. If there is a lot of abdominal fluid, breathing may become increasingly difficult. The feet may become swollen. In advanced pericardial mesothelioma, coughing, worsening breathlessness, palpitations and chest pain may be experienced.

In all types of malignant mesothelioma, generalized symptoms such as fever, unexplained weight loss and fatigue are usually present. Patients with advanced mesothelioma are usually offered palliative treatment to reduce the discomfort from their symptoms. pleural or abdominal fluid collections may be drained, and substances that prevent further formation and collection of fluid may be placed in the pleural or abdominal cavities. Surgery or radiotherapy may reduce some of the obstructive symptoms, and radiotherapy may be used to reduce pain. One or more anti-cancer drugs may also be used. A number of clinical trials are ongoing to find better ways to provide symptomatic relief to people with advanced malignant mesothelioma.