Oncology

Mesothelioma


Mesothelioma - Symptoms and Causes

Mesothelioma (endothelioma or cancer of the pleura) – is a rare disease. Relationship to cancer of the lung – 1:100, 1:200. It occurs at any age but more often after 40 years, predominantly in men.

Pleural mesothelioma is traditionally considered as a rare tumor. On average, in men the incidence is 15-20 cases per 1 million, and among women – 3 cases per 1 million

However, in many countries there is a steady rise in the incidence of mesothelioma of the pleura, which will continue until 2015-2020 in the UK, where the pleural mesothelioma is more common than in other European countries, in 1968 from mesothelioma killed 153 people, in 2003 – already in 1874, and by 2011, researchers predict that the number of deaths will reach 2,450. At the same today in the UK mesothelioma of the pleura in the number of deaths for the year already exceeds melanoma and cervical cancer.

Causes of Mesothelioma

The main etiological factor in the development of pleural mesothelioma is contact with asbestos. The most dangerous amphibole fibers (crocidolite, “blue asbestos”): the narrow straight fibers are easy enough to penetrate through the lymph vessels in the pulmonary parenchyma and subpleural space. According to researchers, 170 tons of produced and consumed asbestos cause one death from pleural mesothelioma.

In addition to asbestos in the development of pleural mesothelioma are also important other chemical carcinogens (silicate, beryllium, liquid paraffin), ionizing radiation (described cases of mesothelioma 20-30 years after radiation therapy of Hodgkin’s disease); genetic predisposition, and actively study the role of the virus SV-40 genes which is expressed in 60% of patients with pleural mesothelioma.

Pathogenesis during Mesothelioma

Pleural mesothelioma develops from the surface epithelium of the pleura (mesothelium), hence the name. The tumor may grow in the form of a node in any part of the visceral or parietal pleura (knotted form) or more diffuse spreads over the pleura, infiltrating it, like a sheath Shrouding the light (diffuse form). If the pleural cavity is free, there is accumulation of serous-fibrinous or hemorrhagic exudate.

Histologically, the tumor usually has the structure of a solid adenocarcinoma, or cancer. In addition, release of the fibrous, tubular, and mixed form of mesothelioma of the pleura. Malignant mesothelioma metastasize to regional lymph nodes (96,5%), another lung and pleura (75%) in the pericardium. Hematogenous metastases occur much less frequently.

Symptoms of Mesothelioma

The disease in the early stage is manifested by pain in the chest and dry cough. Early manifestations of the disease is and exudative pleural effusion, first serous, later haemorrhagic. The increase in the amount of exudate in the pleural cavity causes compression of the lung and shortness of breath. A fairly constant symptom of fever. Often severe phenomena Charcot osteoarthropathy. When the tumor to the mediastinal pleura may develop mediastinal compression syndrome. The disease is usually rapid, the tumor metastasizes early in the pleura, in the mediastinum and distant organs.

The forecast is usually bad. Surgical treatment can give long lasting cure only in a limited, solitary form of tumor in an early stage.

Diagnosis of Mesothelioma

The diagnosis is established on the basis of radiographic studies (after removal of the exudate from the pleural cavity), with the detected tumor nodule from the chest wall, often giving a destruction of the ribs.

Diagnostic Methods and staging of the disease:

Diagnosis of MesotheliomaPlain radiography is considered the reference method of diagnosis, allowing you only to suspect the presence of mesothelioma of the pleura according to the following criteria: thickening of the parietal pleura, hydrothorax, the decrease in the volume of hemithorax, displacement of mediastinum to the affected side.

Computed Tomography (CT) is the main method in the diagnosis and staging of pleural mesothelioma. The most characteristic for pleural mesothelioma are:
– Effusion in the pleural cavity,
– Nodular thickening of the parietal pleura,
– Thickening of interlobar gaps
– The tumor mass surrounding and compressing the lung,
– Reducing the size of hemithorax, shift of the mediastinum.

According to J. Hierholzer, these CT signs allow to identify a PFM with a sensitivity of 93% and specificity of 87%. In assessing T-stage tumors with CT it is possible to identify such features as the growth into the chest wall, invasion into tissue of the mediastinum, the germination aperture and spread in the abdominal cavity. In N-staging CT scan is indicative only method, because the accuracy of CT is only 67%, sensitivity 60%, specificity – 67%. In addition, CT is used to assess hematogenous metastasis.

Magnetic resonance imaging (MRI) it is recommended to use for further local spread of the tumor (T-stage). MRI is more accurate than the CT scan in the evaluation of parameters such as the germination of the soft tissues of the thorax and the degree of damage of the diaphragm. According to Stewart D. et al., MRI allows to exclude T4 with a sensitivity of 85% and a specificity of 100%.

Positron emission tomography (PET) is mainly used to detect nodal and distant metastases. In addition, identification of the metabolically active parts of a tumor helps in identifying areas for biopsy. R. Flores proved essential level of accumulation (SUV) of RFP as one of the prognostic factors. So, patients with SUV < 4, the median survival was 24 months., and patients with SUV > 4 only 14 months. However, the use of modern methods of radiation diagnosis is not always possible to accurately stateroute disease. Thus, according to Van Meerbeck J. et al., compliance with clinical (using CT and MRI) and surgical stage is only 55-75%.

Greatest difficulties arise in the evaluation:
– The degree of involvement of the visceral pleura (T1a/T1b/T2),
– The germination of the internal thoracic fascia (T2/T3),
– The degree of invasion of the pericardium (T3/T4),
– Metastatic lesions of the mediastinal lymph nodes (N0–1/N2–3).

Thus, all cases of mesothelioma of the pleura, diagnosed by clinical and radiological methods of research, require morphological verification of diagnosis, and to improve the accuracy of staging in patients who scheduled surgery, it is advisable to use invasive methods of staging.

Morphological verification of the diagnosis
Cytology pleural fluid in most cases is the first stage of the morphological confirmation of the diagnosis, as many patients have effusion in the pleural cavity. However, the sensitivity of this method is only correspond 26-50%.

Histological verification of the diagnosis. Biopsy of the parietal pleura with a needle Abrams sensitivity (average 50%) is much greater than Cytology. The sensitivity of fine-needle biopsy is 52-57%, and the sensitivity of the needle biopsy under CT/ultrasound – 86%. In addition to low sensitivity, the above methods of biopsy are also characterized by insufficient quantity of material, which leads to difficulty in determining the histological variant of the tumor. Therefore, the main methods of morphological verification of the diagnosis should be considered thoracoscopic or open biopsy.

Thoracoscopic Diagnosis allows to get a sufficient amount of material under visual control, helps to clarify the stage of disease and the assessment of resectability of the tumor gives the possibility of simultaneous execution of pleurodesis, and is also characterized by minimal rate of complications (< 1%). According to Boutin, thoracoscopy allows to verify the diagnosis in 98.4% of cases. If you can’t perform thoracoscopy for the diagnosis verification is used by open biopsy of the tumor, which has an even higher accuracy is 99%.

Invasive staging most important patients, which are planned for extrapleural pneumonectomy (EPP), and allows to reduce the number of obviously non-radical interventions.

What Is Mesothelioma

Standard mediastinoscopy – the most accurate method of assessing the N stage, which is one of main prognostic factors. Mediastinoscopy is significantly superior to CT in accuracy (93% and 67%, respectively), sensitivity (80% and 60%) and specificity (100% and 71%) in the assessment mifogennaja metastasis.

Diagnostic thoracoscopy, in addition to a significant value in diagnosis verification, also plays an important role in the staging of the disease, helping to assess the spread of tumor on the visceral pleura, the tissue of the mediastinum, the diaphragm, the degree of involvement of mediastinal lymph nodes.

Laparoscopy is used by some authors to exclude distant metastases in the abdominal cavity (M1), and also provides a careful assessment of the ipsilateral dome of the diaphragm with the biopsy even in the absence of macroscopic changes.

Invasive staging (mediastinoscopy and laparoscopy) was used Rice D. et al. in 118 patients with pleural mesothelioma recognized as resectable according to radiological methods. Surgical methods of staging revealed stage IV disease (T4/N3/M1) in 13% of patients, which allows to make a conclusion about the need to use invasive methods of staging before surgical treatment.

Differential diagnosis is from disseminated pleural cancer of the lung, exudative pleurisy tuberculous and nonspecific etiology. If a limited form – with tumors and cysts of the mediastinum and chest wall, peripheral lung cancer. Most difficult to differentiate malignant mesothelioma from primary lung cancer accompanied by pleural changes.

In these cases, radiographic methods, tomography and bronchography – allow to detect changes in the lung tissue.

Mesothelioma Treatment

The prognosis of mesothelioma pleural unfavorable, median survival of patients (with symptomatic therapy) is 7 months.

Surgical treatment in the amount of pleurectomy or pleuropneumonectomy is rare in localized forms, only 7-10% of patients. After pleuropneumonectomy surgical mortality reaches 14-15%, significantly higher than the (minimal) mortality of pleurectomy. The life expectancy after these operations are virtually identical: the median survival corresponds to 9-21 months. 2-year survival rate is around 11-45%. Improvement of remote results of surgical treatment (especially of pleuropneumonectomy) is associated with conducting of adjuvant chemotherapy.

Mesothelioma TreatmentExperience surgical, combined treatment (surgery + chemotherapy + radiation therapy) allowed us to develop the following guidelines for mesothelioma of the pleura: Performing extrapleural pneumonectomy (pleuropneumonectomy), holding 4 to 6 weeks up to 6 cycles of chemotherapy with the appointment of platinum drugs, followed by radiation therapy to the area of the remote lung, and mediastinum. Direct mortality, in different groups of comparison, amounted to 5 to 22%, median survival – 21 months. 2-5-year survival was 45 and 22%, respectively. Factors most favorable prognosis are epithelial type of tumor and absence of metastases. Radiation therapy reduces pain, but does not increase life expectancy (increase in dose, as the combination of radiation and chemotherapy does not increase survival).

The effectiveness of modern chemotherapy drugs for mesothelioma of the pleura rarely exceeds 20%. Marked tumor regression and objective improvement, the application of cisplatin, CYCLOBUTANE, mitomycin, raltitrexed (tomudex), etoposide, carboplatin, ifosfamide, vinorelbine, gemcitabine (Gemzar), pemetrexed (Alimta).

Combination chemotherapy is conducted under the scheme: doxorubicin + cyclophosphamide, doxorubicin + ifosfamide, doxorubicin + cisplatin + mitomycin C, campto and cisplatin + mitomycin C, gemcitabine + cisplatin (carboplatin), gemcitabine + Alimta, Alimta + cisplatin (carboplatin). The last 3 schemes are considered the standard treatment for pleural mesothelioma.

In the presence of effusion in the pleural cavity intrapleural possible introduction of cytotoxic drugs or biotherapy drugs to stop or slow down the accumulation of exudate. For this purpose, cisplatin, bleomycin, and – interferon and interleukin-2. The possibility of conducting photodynamic therapy are being researched.

In addition, clinical trials with targeted therapies: Avastin, iressa, Gleevec, thalidomide, etc., which can increase the survival rate. Among targeted drugs should pay attention to the anti-vascular endothelial growth factor. Noted that in pleural mesothelioma with a high level of expression of vascular endothelial growth factor correlates with increased density of capillaries and low survivability. In this context, when we study semaxanib mesothelioma, bevacizumab (Avastin) and thalidomide.

Mesothelioma Prevention

For prophylaxis (prevention) for the development of mesothelioma it is necessary to avoid contact with asbestos at home and at work.