Mesothelioma

Original Editor - Raj Rindani
Top Contributors - Lucinda hampton, Kim Jackson, Manisha Shrestha, Vidya Acharya, Raj Rindani, Adam Vallely Farrell and Rucha Gadgil

Introduction

Mesothelioma, also known as malignant mesothelioma, is an aggressive malignant tumour of the mesothelium, with most tumours arise from the pleura. Mesothelial cells form the lining layers of the viscera (mesothelioma can occur at any mesothelial layer such as the peritoneum or pericardium however the pleural layer is by far the most commonly affected). The subtypes of asbestos strongly associated with malignant mesothelioma are the amosite and crocidolite asbestos.

Mesothelioma

• Affects mostly older individuals who have been occupationally exposed to asbestos.
• Described as an insidious neoplasm because of its long latency period—up to 40 years in some series—after exposure to asbestos.
• Peak incidence occurs in the 5th and 6th decades of life.
• Not genetically transferred

Etiology

Malignant pleural mesothelioma is primarily linked to asbestos exposure

• Some studies suggest that asbestos inhalation causes repeated pleural inflammation, interference with mitosis, activation of proto-oncogenes, and free radical production.
• Other reports indicate associations with ionizing radiation or a germline mutation of BRCA 1 Associated Protein (BAP1).
• Smoking is not linked with malignant pleural mesothelioma, though smoking and asbestos exposure significantly increase the risk of lung cancer.

Professions associated with exposure to asbestos include:

• Shipbuilding
• Mining
• Ceramics
• Cement manufacturer with asbestos
• Auto parts manufacturer, especially that of brake lining
• Paper mill worker
• Insulation work
• Railroad repair

There is no evidence that alcohol, tobacco, or dietary intake is involved in malignant pleural mesothelioma.

Epidemiology

Mesothelioma is uncommon and accounts for 5-28% of all malignancies that involve the pleura.

• There is a strong association with exposure to asbestos fibres (~10% risk during lifetime; 40-80% of patients have a history of asbestos exposure) with risk associated with duration and breadth of exposure. Paraoccupational exposure (e.g. household members of asbestos-exposed workers) can also occur.
• Not all types of asbestos are strongly implicated, with crocidolite being the main causative fibre type. Given the sources of asbestos exposure being predominantly mining, construction, lagging and machinery mechanics, 60-80% of cases are encountered in males, in general, 20 to 35 years after exposure. Some areas of the world have very regional hotspots, such as Belfast in Northern Ireland, due to the historic shipbuilding industry.
• There is also increased risk for those with household exposure (e.g. family of exposed workers).
• There has been no convincing evidence for an association with smoking

Pathogenesis

Mesothelial cells are much more susceptible than other cell types to asbestos cytotoxicity. When asbestos and other fibers reach the pleura and peritoneum through lymphatics, they remain in place for months or years, triggering a chronic inflammatory process that helps in the production of mutagenic oxygen radicals induced by asbestos are responsible for asbestos pathogenesis and carcinogenesis.

• Asbestos fibres are inhaled and migrate to the pleura.
• Within the pleural space, fibres cause irritation and a repeated cycle of tissue damage and repair is established.
• The presence of oxygen free radicals, released by asbestos fibres when phagocytosed by macrophages, causes intra-cellular DNA damage and abnormal repair.
• Asbestos fibres also penetrate mesothelial cells, where they interfere with mitosis, generate mutations in DNA and alter chromosome structure.
• Asbestos-exposed mesothelial cells release inflammatory cytokines(eg tumour growth factor-β, platelet-derived growth factor, vascular endothelial growth factor) creating a favourable microenvironment for tumour growth.
• Finally, asbestos induces the phosphorylation of various protein kinases, leading to increased expression of proto-oncogenes and further promotion of abnormal cellular proliferation.

Signs and Symptoms

Common signs and symptoms of Pleural mesothelioma are:

• Chest wall pain
• Pleural effusion, or fluid surrounding the lung
• Shortness of breath
• Fatigue
• Wheezing, hoarseness
• Blood in the sputum (fluid) coughed up (hemoptysis)
• Dry cough
• Weight loss

Diagnosis

Diagnosis of mesothelioma is difficult to make. Radiological imaging (X-ray, ultrasound, Ct scan, positron-emission technology (PET)-CT or magnetic resonance imaging (MRI) ) can provide valuable diagnostic and staging information.

Histology is a reliable prognostic marker. 

Treatment and Prognosis

Treatment continues to be challenging and the long-term survival is poor. Single modality treatment (surgery, radiotherapy, chemotherapy, immunotherapy and even photodynamic therapy) have not been shown to improve survival. More recently multi-modality treatment has had some impact on favourable subgroups (early disease, and epithelioid histology). Treatment includes:

• extrapleural pneumonectomy
• adjuvant chemotherapy
• radiotherapy

The prognosis is poor for all tumour types with a median overall survival without treatment of 4-12 months. In favourable patient subgroups up to 45% 5-year survival may be achievable, however even with aggressive multi-modality therapy overall 5-year survival remains poor (3-18%) 3 with a median survival time of approximately 18 months.

Physiotherapy management

Physiotherapy is an integral part of the multidisciplinary approach treatment for patients with cancer.

All patients who suffer from mesothelioma are required to undergo physical therapy, even if you have already undergone surgery, chemo, and/or radiation. There is a valid reason for this. All three types of treatment are exceptionally difficult on your body. With their many negative side effects, your body needs physical therapy to regain the strength it once had. Without physical therapy, these treatment options are less successful. Your body needs all the strength it can get to successfully respond to all treatment options. This therapy will occur with a physical therapist as scheduled by your medical professional. Mesothelioma treatments are designed to help patients feel more comfortable and hopefully extend your quality of life. While there is no cure for mesothelioma at this time, these three treatment options are your best bet. Of course, your doctor might have other suggestions as far as using a combination of these treatments and other medications to help you live as comfortably as possible. Each case of mesothelioma is unique, meaning your treatment method will differ from others.

Respiratory care, pain, improve the patient level of fatigue, improve bodily muscular and cardiovascular endurance are some goals that need to be kept in mind for patients with mesothelioma.