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 is a form of cancer that appears in the epithelial layer called mesoderm that lines the pleurae, peritoneum, and pericardium. Mesothelioma affects mostly older individuals who have been occupationally exposed to asbestos. Mesothelioma has been described as an insidious neoplasm because of its long latency period—up to 40 years in some series—after exposure to asbestos. It arises in the mesothelial surfaces of tissues in the pleura but can also occur in the peritoneum and the tunica vaginalis. Peak incidence occurs in the 5th and 6th decades of life.

It is not genetically transferred rather caused by long-duration exposure to asbestos and other carcinogenic fibers. 400 different mineral fibers are present in nature and among them, these 6 fibers (amphiboles fibers [crocidolite, actinolite, tremolite, anthophyllite, and amosite] and serpentine fibers [chrysotile]) collectively known as asbestos for regulatory purpose. These 6 fibers were banned to use commercially after 1980s.

Malignant pleural mesothelioma (MPM) is an aggressive cancer of the pleural surface. It is associated with previous asbestos exposure, with a latency period of ∼40 years between fibre exposure and disease presentation.

Epidemiology

Approximately 3000 incident cases of mesothelioma are registered each year in the United States. The incidence rate varies between less than 1 case per 100,000 persons in states with no asbestos industry to 2 to 3 cases per 100,000 persons in states with an asbestos industry. The mean age of death from mesothelioma in the United States was 72.8 years, with a male‐to‐female (M: F) mortality ratio of 4.2:1, as men were traditionally more likely to be employed in trades involving asbestos exposure.

Between 1994 and 2008, age‐adjusted mesothelioma mortality rates increased by 5.37% per year worldwide. In a meta-analysis, a significantly increased risk of pleural mesothelioma was reported for both household exposure and neighborhood exposure. Different strengths of association were observed according to fiber type, with the strongest associations noted when amphibole was present and the weakest when chrysotile was present. Therefore, the types of fibers to which residents are exposed to influence mesothelioma rates. Crocidolite and amosite fibers are considered the main cause of mesothelioma among occupationally exposed individuals (mining, road construction, off‐road driving, etc).

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, including tumour growth factor-β, platelet-derived growth factor and vascular endothelial growth factor (VEGF). This creates a favourable microenvironment for tumour growth. Finally, asbestos induces the phosphorylation of various protein kinases (mitogen-activated protein and extracellular signal-regulated kinases 1 and 2), 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. 

Prognosis

The Mesothelioma prognosis remains disappointing, although there have been some modest improvements in prognosis from newer chemotherapies and multimodality treatments.

Treatment

The role of surgery in pleural mesothelioma is controversial as it is difficult to predict who will benefit from aggressive management, even when local therapies are added to existing or novel systemic treatments. Treatment outcomes are improving, however, for peritoneal mesothelioma. Multidisciplinary international collaboration will be necessary to improve prevention, early detection, and treatment.

There is various medical management for mesothelioma. Chemotherapy is the only treatment modality that has been shown to improve survival in MPM. targeted therapy has recently shown a positive impact. Radiotherapy is used in two main settings in MPM: as a palliative measure to treat symptoms or an adjuvant to surgery and chemotherapy in the context of trimodality treatment. The benefit of surgery in MPM is much debated, and there is a need for robust randomised trial data to elucidate its efficacy and clarify its role in management. Some surgical procedures are extrapleural pneumonectomy (EPP),extended pleurectomy with decortication, and partial pleurectomy via VATS.

Physiotherapy management

Physiotherapy is an important part in Mesothelioma treatment.
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.