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02.05.2015

Pleural mesothelioma - Modern treatment tactics


Mesothelioma  as cancer was first described in 1870. It is more common pleural than the peritoneum, with a predominance of right-sided. Men suffer more than women in a ratio of 8: 1. Mesothelioma can occur at any age, even in children 2-4 years. In the etiology of mesothelioma primary importance is the duration of exposure to asbestos and erionite mineral used in construction practice. Etiological factors of mesothelioma are genetic predisposition, as well as simian virus SV40.

In Russia, the epidemiology of this tumor has been overlooked. Meanwhile, according to the literature, in the United States, where asbestos professionally exposed to 7-8 million. People, the incidence of malignant mesothelioma (mesothelioma) is 0.1-0.2 per 100 thousand inhabitants, and is increasing annually (peritoneum and pleura are affected equally often ). Since 1976, in France this pathology attributed to occupational diseases (B. Saillard et al., 1977). The latency period of malignant mesothelioma is 20-30 years.

The pathogenesis of pleural mesothelioma

The pathogenesis of pleural mesothelioma has not been studied, however, it found that asbestos fibers have tropism for serous membrane. Respiratory they migrate to pleura, which can accumulate in large quantities and serve as a trigger for the development of tumors. Thanks lymph flow directed towards the parietal pleura, the tumor cells are implanted in her and gradually spread over the entire surface. Thus, in the neoplastic process involves both visceral and parietal pleura, which leads to disruption of lymph circulation, the rapid accumulation of fluid in the pleural cavity.

According to the histological WHO classification (1999), malignant mesothelioma (mesothelioma) are divided into the following variants (types):

     Epithelioid type, constituting 50-70% of all mesothelioma and has the best prognosis (outcome)
     Sarcomatoid type (7-20%)
     Mixed (20-35%)

The most frequent adverse is sarcomatoid variant of the tumor. Pleural effusion occurs in 60-80% of patients, but gradually growing tumor can cause complete obliteration of the pleural cavity.

Risk factors for malignant mesothelioma

Exposure to asbestos is the major risk factor for mesothelioma. Asbestos is used in the manufacture of insulation and refractory materials, tiles, brake pads and so on. After the establishment of the relationship of exposure to asbestos and the development of mesothelioma is the use of the substance fell sharply.
The risk of developing mesothelioma depends on the intensity and duration of exposure to asbestos. Long-term exposure at a young age greatly increases the risk of mesothelioma. The period of time from the time of first contact with asbestos before tumor diagnosis is 20-50 years.
Smoking by itself does not affect the increase in the incidence of mesothelioma, but the combination of smoking and asbestos exposure significantly increases the risk of lung cancer. In smoking men exposed to asbestos, the risk of lung cancer increased 50-90 times compared to the general population.
For prophylaxis (prevention) of developing mesothelioma is necessary to avoid exposure to asbestos at home and at work.

Mesothelioma Diagnosis

Early symptoms of mesothelioma are not specific. These patients are often ignored or taken for acts of ordinary non-neoplastic diseases. Most patients with mesothelioma symptoms appear within 2-3 months prior to the detection of tumors.
In some patients the symptoms may persist for 6 months or more.
Approximately 50% of patients with pleural mesothelioma noted pain in the chest on the side or rear surface. Many patients complain of shortness of breath. In some cases, there is difficulty swallowing, cough, sweating, weakness, weight loss and fever.
Other symptoms can point to hoarseness, coughing up blood, swelling of the face and upper limbs.
Patients with peritoneal mesothelioma can be abdominal pain, nausea, vomiting, weight loss. Some patients may receive the fluid in the abdomen (ascites), and / or swelling.
If you suspect that mesothelioma is an urgent need to see a doctor, who will find out the presence of risk factors and order tests.

During the examination, the doctor can detect the presence of fluid in the pleural cavity (pleurisy), abdomen (ascites) or the pericardium (pericarditis), which arises as a result of tumor development.
Chest X-ray can detect thickening of the pleura, the presence of calcifications (mineral deposits) and pleural fluid in the pleural cavity.
Computed tomography (CT) allows diagnosis of mesothelioma and to determine the prevalence of the process (stage).
Magnetic resonance imaging (MRI) can help identify lesions diaphragm - the muscle tissue that separates the chest and abdominal cavity.
Thoracoscopy (examination of the pleural cavity using a special device) can not only identify the tumor, and a biopsy (take a piece of tissue for examination) or to obtain fluid for microscopic examination to confirm the diagnosis.
Laparoscopy (examination of the abdominal cavity using a device) you can inspect the abdominal cavity, take a piece of the tumor or fluid for research.

Stages (prevalence), mesothelioma

Currently only distinguish stages of pleural mesothelioma, as occurs much more often than other sites.
There are 4 stages of pleural mesothelioma.
Stage I - the tumor affects the pleura, left or right, and the lymph nodes are not involved in the process.
Stage II - one-sided defeat of pleura and spread of the tumor on the diaphragm or lung tissue.
Stage III - one-sided defeat of pleura and distribution process on the anterior chest wall, or adipose tissue of the mediastinum, or pericardium, or lymph nodes on the side of mesothelioma.
Stage IV - mesothelioma involves the process of muscle or ribs, or invades the diaphragm, or the esophagus, trachea, thymus, large blood vessels, or spine, or moves to the other side, or spread through the bloodstream to distant organs.

Treatment of malignant mesothelioma
The choice of tactics of treatment depends on several factors, including the stage of the tumor, patient's general condition and his opinion. Given the rarity of mesothelioma, it is advisable to treat cancer in specialized institutions that have experience in treating such patients.

Surgical treatment

The operation can be performed as a palliative and therapeutic purposes. Under palliative operation meant surgery, that can be used to eliminate or reduce pain or discomfort caused by tumor growth.
Such operations are used if you can not remove the tumor because of the prevalence of severe or the patient's condition.

Plevroektomiya / decortication is usually and palliative surgery involves the removal of the pleura, which prevents the accumulation of liquids and decrease pain.

Thoracentesis - a procedure in which a needle is removed fluid from the pleural cavity to facilitate the patient's condition.

The introduction of talc or antibiotics into the pleural cavity to temporarily prevent the accumulation of fluid in it is effective in 90% of patients with pleural mesothelioma.

Puncture the anterior abdominal wall allows you to remove the accumulated fluid in the abdomen in patients with peritoneal mesothelioma.


Patients with pericardial mesothelioma pericardiocentesis execution provides the ability to remove fluid and improve heart function.

Patients in satisfactory condition with a localized tumor radical operations, ie complete removal of mesothelioma.
It should be noted that often after the alleged radical operations are microscopic tumor foci. In this regard, the value of radical surgery in patients with mesothelioma contested.

Vneplevralnaya pneumonectomy is the removal of the pleura, diaphragm, pericardium and lung on the affected side. This extended operation can only be performed by highly skilled surgeons, oncologists, patients with good general condition without serious comorbidities.

Patients with localized mezotelimoy peritoneum may be an attempt to remove the tumor together with a part of the abdominal wall. Unfortunately, most patients with mesothelioma peritoneum performance of radical surgery is not possible due to the prevalence of the process.

In the case of localized lesions of the pericardium is performed its removal, and in advanced process - palliative interventions that prevent the accumulation of fluid.

Radiation therapy
External radiation is used in patients with mesothelioma most often.
With internal radiation radioactive material is applied directly to the tumor.
This type of radiation therapy is used as the primary method of treatment for patients in critical condition, when they can not move a serious operation.

Auxiliary radiotherapy administered after non-radical operation to destroy the remaining cancer cells.
Palliative irradiation is used to relieve symptoms caused by tumor growth: shortness of breath, pain, bleeding and difficulty swallowing.

Radiation therapy can cause adverse reactions and complications in the form of skin burns, weakness, nausea, vomiting, loose stools, damage lung tissue, difficulty breathing.
The majority of adverse events being held after completion of the irradiation.
You should know that radiation therapy may aggravate side effects of chemotherapy.

Chemotherapy

In the treatment of patients with malignant mesothelioma chemotherapy can be administered not only intravenously, but intrapleural and intraperitoneally (into the abdominal cavity).
Depending on the stage of the tumor, chemotherapy may be as basic and auxiliary treatment. Moreover, chemotherapy is used only as a palliative, giving only a temporary effect.

Of the anticancer drugs used: doxorubicin, cisplatin, methotrexate, vinorelbine, et al. In various combinations.

Adverse reactions of chemotherapy include: nausea, vomiting, loss of appetite, hair loss, sores in the mouth, increased susceptibility to infections, bleeding.
The majority of adverse events being held after completion of treatment.

Surgical treatment in the volume or plevrektomii plevropnevmonektomii are rare in localized forms, only in 7-10% of patients. After plevropnevmonektomy operative mortality reaches 14-15%, significantly higher than the (minimum) plevrektomy mortality. Life expectancy after these operations do not differ: the median survival corresponds to 9-21 months .; 2-year survival rate is 11-45% (Giaccone G., 2002; Rahman M. et al., 2003). Improving long-term results of surgical treatment (primarily plevropnevmonektomy) associated with adjuvant chemotherapy.

Experience of surgical, combined treatment (surgery + chemotherapy + radiotherapy) * allowed to develop the following recommendations for pleural mesothelioma:

 1. Extrapleural pneumonectomy Execution (plevropnevmonektomii), holding 4-6 weeks up to 6 cycles of chemotherapy with the appointment of platinum, followed by radiotherapy in the area of ​​remote lungs and mediastinum. Direct mortality in different comparison groups was 5-22%, median - 21 months., 2-5-year survival rate - 45 and 22%, respectively. The factors most favorable prognosis are the type of epithelial tumors, as well as the absence of metastases.
2.  Radiotherapy (ODS to 50 Gy.) Reduces the pain, but does not prolong life (increased dose, as well as a combination of radiation and chemotherapy did not improve survival).
3.  The efficiency of modern chemotherapy for pleural mesothelioma rarely exceeds 20%. Marked tumor regression and objective improvement in the application of cisplatin, cycloplatam, mitomycin, raltitreksida (tomudeksa), etoposide, carboplatin, ifosfamide, vinorelbine, gemcitabine (Gemzar), pemetrexed (Alimta).
4.  Combination chemotherapy is performed by the schemes: doxorubicin + cyclophosphamide, doxorubicin, ifosfamide, doxorubicin and cisplatin + - mitomycin C, cisplatin kampto + mitomycin C, gemcitabine and cisplatin (carboplatin), gemcitabine + Alimta, Alimta and cisplatin (carboplatin). Last 3 schemes are considered the standard treatment of pleural mesothelioma.

In the presence of pleural effusion may intrapleural administration of cytostatic drugs or biotherapy to stop or slow down the accumulation of fluid. For this purpose, cisplatin, bleomycin, and - interferon and interleukin-2. Possibilities of photodynamic therapy investigated.

In addition, in clinical trials targeted drugs: Avastin, Iressa, Gleevec, thalidomide, et al., Which can increase the survival rate. Among the targeted therapies should pay attention to inhibitors of vascular endothelial growth factor. It is noted that pleural mesothelioma high level expression of vascular endothelial growth factor correlates with increased capillary density and low survival. In this regard, with mesothelioma studied semaksanib, bevacizumab (Avastin) and thalidomide.

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