mesothelioma Definition

Mesothelioma is a unique cancer that starts from the mesothelium, the membrane lining the body cavities contain. Mesothelioma arising from the pleura (lining of the lungs), pericardium (sac around the heart), peritoneum (abdominal lining), and the tunica vaginalis testis (lining of the male reproductive organs). The majority of mesothelioma cases from the pleura.
Epidemiology and cause of mesothelioma
Mesothelioma occurs everywhere in the world. In the United States, it is estimated that ~ 3000 new cases of mesothelioma every year. Western Europe has more than 5000 new cases / year and China is estimated 4000 new cases / year.

The main cause of mesothelioma is well established and the environment, patients are often exposed to asbestos fibers in their work or living space. Asbestos is a long thin silicate minerals and is linked not only mesothelioma, but also to pneumoconiosis and lung cancer. Asbestos was a popular material used in insulation and construction that the desired properties of heat / fire and chemical resistance. The fibers are dangerous when they are in the air and be inhaled or swallowed. There are two major classes of asbestos: serpentine and amphibole. Serpentine minerals (chrysotile) account for 95% of asbestos in buildings in the United States. The amphibole group consists of five types of asbestos - amosite, crocidolite, anthophyllite, tremolite, actinolite and. Amosite asbestos is called the brown and can be found in building materials. The nature of most carcinogenic asbestos amosite and crocidolite. However, chrysolite is dangerous and is linked to the development of mesothelioma in humans.
In more rare cases, there are reported cases of mesothelioma occurring from genetic inheritance (Capaddocia region of Turkey) and possibly also by exposure to Simian Virus 40 (SV40).
Mesothelioma has a long latency from the time of exposure to asbestos - The median time from exposure to the development of mesothelioma is 32 years. Most patients develop mesothelioma between 20 to 50 years after known exposure to asbestos.
Most patients develop mesothelioma between the ages of 40 to 80. If asbestos was used mainly in construction, military and production of materials, there is a higher incidence of mesothelioma in men than in women (3:1).
Screening and Prevention
There are currently no standard screening tests in use. However, two blood tests in research. Osteopontin, a glycoprotein that mediates cell matrix interactions, are higher in mesothelioma patients serum compared with asbestos miners who do not have the cancer. Soluble mesothelin-related peptide (SMRP) and osteopontin test is more than able to mesothelioma patients who relapsed after surgery to identify.
There are currently no chemoprevention agents available for mesothelioma.
Types of pleural mesothelioma
It is crucial to the diagnosis of mesothelioma to patients as quickly as possible. Mesothelioma is often confused with other forms of cancer, or benign conditions.
Many patients have symptoms of cough and shortness of breath and chest x-rays show fluid, called pleural effusion. Often the fluid persists, even after drainage and the evaluation of the fluid often show cancer cells and is mistaken for a benign condition. Whether the fluid contains cancer cells and is confused with another cancer diagnosis of adenocarcinoma. If a patient has a possible diagnosis of mesothelioma, it is essential to be evaluated at a cancer center that treats mesothelioma patients and has the expertise to get the right diagnosis.
There are certain pathology techniques that can be done to assist in making the correct diagnosis: electron microscopy and immunohistochemical markers. Immunohistochemistry uses antibodies to bind to specific proteins in the tissue. Some of the specific markers that are positive in mesothelioma cytokeratin 5 / 6, calretinin, and WT-1. Mesothelioma is usually negative for CEA, Leu-M1, and TTF-1.
There are three main histological types of mesothelioma: epitheliod, sarcomatoid and biphasic.
The most common type is epitheliod occurs in 60-75% of cases. Occurs in 15-20% biphasic and sarcomatoid occurs in 10-15% of cases. Epitheliod tumors generally have the best prognosis, while sarcomatoid tumors are thought to be more aggressive. Phenotypes have characteristics of both biphasic and sarcomatoid tumors epitheliod.
Diagnostic tests
The usual symptoms of mesothelioma include shortness of breath, coughing, weight loss, loss of appetite and fever. These symptoms are often found in other conditions and may hinder making the correct diagnosis of mesothelioma. For example, recurrent pleural effusion (fluid in the pleural space) may occur in benign conditions of congestive heart failure and pneumonia.
Part of the diagnosis of mesothelioma can include:
- Assessment of medical history with a focus on previous exposure to asbestos and occupational risks
- Physical examination
- Chest x-ray
- Chest Computed axial tomography (CT) scan
- Positron emission tomography (PET-CT)
- Magnetic resonance imaging (MRI)
- Biopsy of the tumor tissue (a biopsy needle or drainage of pleural fluid)
- Thoracoscopic surgery for a biopsy
- Mediastinoscopy (biopsy of the lymph nodes in the chest)
- Laparoscopy (abdominal cavity to evaluate the transdiaphragmatic spread of mesothelioma)
- Pathological review of tumor cells to cytology or biopsy
Staging pleural mesothelioma
There are several classification systems tend to mesothelioma. Staging is essential for a patient to determine treatment. The stage is determined by the radiographic images and possibly also by the surgical biopsies and evaluation of mediastinal lymph nodes and abdomen.
The most commonly used staging system of the International Mesothelioma Interest Group (IMIG) for the American Joint Committee on Cancer (AJCC). This system uses the TNM (tumor, node, metastases) classification.
Stages of Pleural mesothelioma
Phase 1a: Tumour concerns the outer layer of the pleura (parietal pleura), but does not involve the pleura to the lung (visceral pleura).
Phase 1b: Tumor concerns the parietal and visceral pleura.
Stage 2: Tumor invades the lungs and diaphragm (the thin muscle that separates the chest from the abdomen).
Stage 3: Tumor penetrates the fibrous sac around the heart (pericardium), chest wall (in one area only) or keep the lymph nodes in the chest.
Phase 4: Tumor consists of several areas of the chest wall, stretches across the membrane or the pericardium, by other organs like the heart, trachea or esophagus, or has spread to other organs like the liver or lungs opposite .

Types of surgical intervention
There are diagnostic, palliative, and definitive surgery.

Diagnostic procedures:
Patients often need a thoracic surgeon to assist in making the diagnosis of mesothelioma. Some of the procedures for both diagnosis and stage of the patient include the following:
- Thoracentesis (needle drainage of pleural fluid)
- Core biopsy needle (larger needle biopsy of the tumor)
- Video-assisted thoracoscopy (VATS) - surgery to remove the tumor in the breast biopsy
- Mediastinoscopy - biopsy of the lymph nodes in the middle of the chest
- Endobronchial ultrasound (EBUS)-guided biopsy - a different method to sample biopsy of the lymph nodes in the middle of the chest
- Laparoscopy - operation through tiny cameras through small (0.5 to 1.5 cm) incisions in the abdomen, used to evaluate the spread of cancer in the abdomen

Palliative procedures:
In patients who can not receive complete removal of the tumor pleural mesothelioma, fluid re-accumulation is a problem and leads to symptoms of breathlessness and pain. Some of the procedures that can be done as follows:
- Placement of an indwelling chest tube or catheter Denver repeated drainage of pleural fluid can
- Pleurodesis, injection of a material (often talc) into the pleural cavity and destroys and prevents further moisture accumulates.

Definitive surgical procedures:
Because pleural mesothelioma is a large tumor around the lungs, it is extremely difficult to remove surgically. Patients with mesothelioma to seek surgical opinions of thoracic surgeons who are trained to treat mesothelioma and experience in performing these operations have. There are two main types of surgery to remove the gross tumor. It is discussed whether these procedures are curative in nature, but there are long-term survivors have received this type of operation. There are several criteria beyond the stage that determine whether a patient mesothelioma is a candidate for the final surgery.

- Pleurectomy / decortication (P / D) - requires an open thoracotomy with removal of the parietal pleura, pleura of the mediastinum, pericardium, and diaphragm, and the visceral pleura. Often this type of operation leaves behind tumor tissue and is considered a palliative rather than curative approach. However, recent retrospective studies have shown long-term survivors who had mesothelioma P / D.

- Extrapleural pneumonectomy (EPP) - removes en bloc the parietal and visceral pleura, the lung, mediastinal lymph nodes, diaphragm and pericardium. The diaphragm and pericardium are then reconstructed. This surgical procedure involves a considerable risk with a high degree of cardiac and pulmonary complications. The 30-day mortality ranges from 3.4 to 8% in experienced cancer centers. In inexperienced hands, the mortality rate is higher rated about 18 to 20%. Selection of patients for this type of surgery requires careful analysis and a thorough cardiopulmonary assessment.
Types of radiation
After surgery, radiation therapy is necessary to eliminate any microscopic disease. There are two main types of radiation therapy in mesothelioma are administered to the hemithorax: external and intensity-modulated radiotherapy (IMRT). Patients who require an EPP entire hemithorax irradiation between 4 to 8 weeks after surgery. The use of radiation after P / D or breast biopsy remains controversial. The reason is that patients who have had a P / D have their lungs are still intact and the amount of radiation to the chest can be administered in the presence of the lungs is limited. Often, radiation oncologists will be limited to radiotherapy high-risk areas, such as the locations where a chest wall incision was made. These sites have a high risk of tumor seeding and tracking through the chest wall with painful results.Forms of systemic therapy for pleural mesothelioma
Mesothelioma is not cured by chemotherapy, but it can be stabilized for a period of time and in some cases, the tumor may respond to chemotherapy or targeted agents. Historically, the most effective chemotherapy used in combination. Those most commonly used today include: platinum agents (cisplatin, carboplatin), pemetrexed (Alimta), gemcitabine (Gemzar) and vinorelbine (Navelbine). In the past, older chemotherapy used included doxorubicin, mitomycin, cyclophosphamide and ifosfamide.
For unresectable disease:
Neoadjuvant (before surgery), chemotherapy was investigated in several clinical trials. These studies have used platinum doublets with gemcitabine or pemetrexed. Response (defined as tumor shrinkage), between 26-33% have been reported. However, the median survival for all patients with neoadjuvant chemotherapy, surgery, radiation and still low at ~ 17 months. In the subgroup analysis of the largest of these clinical trials, the median survival of patients who responded to neoadjuvant chemotherapy was higher in 23 months. This finding indicates that more effective systemic therapies can improve survival for mesothelioma patients.
There are ongoing clinical trials in patients with resectable mesothelioma bring new oral targeted agents (see below) in addition to surgery, chemotherapy and radiation. Patients with mesothelioma are encouraged to participate in clinical trials.
For unresectable disease:
The current standard front-line chemotherapy in the United States, cisplatin-pemetrexed (pemetrexed 500 mg/m2 and cisplatin 75 mg/m2). This chemotherapy is administered in combination with vitamin supplements (vitamin B12 and folic acid) and improves the median survival of mesothelioma patients to 1 year. The main side effects with this regimen are neutropenia (low white blood cell count), anemia (low red blood cell count), nausea, vomiting, fatigue and stromatitis / rash. Sometimes carboplatin (another platinum agent) are replaced with cisplatin as a patient is allergic or intolerance to cisplatin. Several clinical trials are currently underway that new targeted agents combined with platinum-pemetrexed.
When a patient develops mesothelioma progression or refractory to platinum-pemetrexed, the next step would be to switch agents. There is currently no set standard of care for the next treatment. Medical oncologists may consider treatment with single agent gemcitabine, vinorelbine or pemetrexed (if the patient does not receive pemetrexed in the frontline setting). Clinical trials in this setting are highly encouraged.
New agents and clinical trials
There are several new classes of targeted agents in research. One class focuses on the angiogenesis pathway. Angiogenesis is the formation of new blood vessels and therefore focused on the potentially starve the tumor angiogenesis pathway. There are several agents under active investigation. To determine whether you are a candidate for a clinical trial, talk with your medical oncologist.
List of new substances is examined:
Bevacizumab - a monoclonal antibody to vascular endothelial growth factor (VEGF) objectives. It is administered intravenously and is combined with other chemotherapy, usually every 3 weeks. Mesothelioma has the highest expression levels of VEGF in the solid tumors. Bevacizumab is FDA approved for non-small cell lung cancer, breast cancer, colon cancer, gastrointestinal cancer, and glioblastoma.
Cediranib - an oral VEGF receptor (VEGFR) and platelet derived growth factor receptor (PDGFR) inhibitor. This is taken every day. Clinical trials are ongoing combining this agent with chemotherapy or by himself.
Sorafenib - an oral VEGFR, PDGFR, Raf inhibitor. Sorafenib is FDA approved for use in renal and hepatocellular cancer.
Sunitinib - an oral VEGFR, PDGFR, KIT inhibitor. Sunitinib is FDA approved for use in renal cell carcinoma and imatinib-resistant gastrointestinal stromal tumor (GIST).
Imatinib mesylate - an oral BCR-ABL, KIT, and PDGFR inhibitor. Imatinib is FDA approved for use in CML and GIST.
Dastinib - a multitargeted kinase inhibitor of Src, PDGFR, ephrin kinases, KIT is FDA approved for use in imatinib-refractory CML.
Pazopanib - a VEGFR, PDGFR and KIT inhibitor.
Vatalanib - a VEGFR, PDGFR and KIT inhibitor.
Other resources in research:
Vorinostat - a histone deactylase inhibitor. Vorinostat is FDA approved for use in T-cell lymphoma. A large phase III trial is underway evaluating Vorinostat in the second-and third-line setting.
Everolimus - an mTOR inhibitor. Everolimus is an immunosuppressant used to prevent rejection of transplanted organs.
Bortezomib - a proteosome inhibitor. Bortezomib is FDA approved for use in multiple myeloma and mantle cell lymphoma.
Gene therapy (IFN-b-HSV thymidine kinase adenoviral vectors) - injected directly into the pleural space.
Anti-mesothelin antibodies (SS-1) - mesothelin, a protein present on mesothelial cells and overexpressed in mesothelioma tumors. SS-1 targets mesothelin