Pleural mesothelioma is a rare disease that occurs more often in men aged 60 years. It is expected that over the next 30 years in Western Europe it will die about 250 000 people. Morbidity in Bulgaria is low, with about 15 new cases per year. In over 80% of patients showing asbestos (amfibolni fiber Chrysolites particular), with a time of contact with asbestos products the appearance of the disease is sometimes 30-40 years. The mechanisms of oncogene-induced asbestos-inde are not well understood. It is assumed that the asbestos fibers may also play a role as an initiator and a promoter in tumor processes. As etiologic agents were studied fiber and other minerals (zeolite) radiation torotrasta, beryllium and others.
Macroscopic two different forms of malignant pleural mesothelioma - localized and diffuse. Localized tumors are the most common benign, but there are malignant variants.
Typical cancer of the pleura is a mesothelioma diffusion. He has expressed invasive growth to underlying structures, metastasize rapidly through blood and mediastinal lymph nodes. Death occurs by engaging the vital organs in the chest between 4 and 12 months after diagnosis, even with best supportive care.
Diffuse malignant mesothelioma
Pathomorphology. Malignant mesothelioma is grouped into three histological subtypes: a) epithelial - 50-70% b) sarkomatoiden (fibrosarkomatozen) - 15-20% c) mixed (biphasic) - 20-30%.
The specificity of mesothelioma cells is the production of hyaluronic acid, which is used for specific staining in histologic examination. To distinguish the diagnosis of adenocarcinoma necessary immunohistochemical assay and electron microscopy. Cytology prevralen punctate not sufficiently informative and can not be used for final diagnosis. For histologically confirmed diagnosis is considered only obtained from a study of biopsy prevralna.
Clinic. clinical picture of malignant pleural mesothelioma is insidious and nonspecific. Chest pain and shortness of breath, which is not a characteristic of pleural are the most common initial symptoms. Typically, patients are asymptomatic or with physical random X-ray data detected pleural effusion which was observed in 95% of cases, a massive effusions are rare. In the beginning patients complain of shortness of breath, breathlessness is a type of restrictive due to compression and coverage of the lung. Chest pain speak for advanced disease. It can become very strong unbearable because of the abundance of bolevi rezeptori in the parietal pleura or chest wall invasion. Cough (painful, unproductive), fever and weight loss are common symptoms. In advanced disease, symptoms of compression and sprouting of mediastinal organs and structures: dysphagia, pericardial effusion, rhythm and conduction disturbances, paresis of the diaphragm syndrome v. cava superior, hoarseness (nerve paresis of return) syndrome Horner. ascites caused by overgrowth of the tumor directly through the diaphragm, or contralateral poured into the chest caused by metastases in the opposite pleura are other signs and symptoms of advanced disease
Diagnosis. diagnostic algorithm in pleural mesothelioma include the following several methods.
Imaging methods. Radiographic signs are nonspecific: pleural effusion from the affected side, pleural seals or soft tissue lesions originating from the pleura. With its high spatial resolution CT allows visualization of discrete changes in the course of pleural sheets. The involvement of the mediastinum can be represented as a direct infiltration of the mediastinal pleura (Fig. 1) or by increasing the mediastinal lymph nodes. In advanced cases of pleural thickening results in compression of the lung (lung blocked). CT and MRT allows the simultaneous display of all the structures that make up the rib cage - pleural sheets, pericardium, lung parenchyma, bones and muscles, and upper abdomen. Multiplanarnite reconstruction in CT and MRI scans directly provide detailed preoperative evaluation. CT and MRI criteria for resectability of the tumor are: a) disengaged ekstraplevralna fat b) normal CT images and normal intensity MRI visualization of the structures that surround the tumor, c) lack of involvement of soft tissue ekstraplevralnite d) smooth diaphragm surface in sagittal and tranzverzalni cuts.
Positron emission tomography (PET) is a method with better sensitivity for staging of patients who are aggressive treatment. Malignant mesothelioma is like confectionery with high absorption (SUV) in comparison with benign tumors of the pleura. These high levels of absorption, and show the presence of metastases in mediastinal lymph nodes (N2). In a large percentage of cases, PET can detect distant metastases missed by other imaging methods.
In recent years, highlighting the advantages of integrated CT-PET scanning in the preoperative assessment of patients who are maximal cytoreductive therapy. This technique has a very high sensitivity and specificity in the differential diagnosis of malignant from benign pleural tumors. However, it can not distinguish mesothelioma from adenocarcinoma, are also possible false-positive results in inflammatory pleural disease.
Thoracic ultrasound and echocardiography are useful for suspected involvement of the pericardium and heart and evaluation of pleural effusion and control of the needle in diagnostic needle biopsy.
Methods for morphological diagnosis. Pleural puncture with ditologichno and biochemical examination of punctate are limited role (accuracy 62%) as malignant cells in pleural fluid have only 30-40% of patients with diffuse mesothelioma.
Pleural biopsy needle or biopsy with about 85% accuracy. In these cases, there is a high likelihood of developing metastatic implantation in the chest wall (Fig. 2), therefore it is recommended that prophylactic topical exposure [1].
VATS pleural bioposiya under visual control with a sensitivity up to 98% and most surgeons consider it to be the method of choice. It can also be accomplished through a fertilizer-koport under local anesthesia and sedation of the patient.
In most patients with thickened pleura and without pleural effusion recommended open biopsy through a small thoracotomy. procedure is almost the same diagnostic sensitivity. Rarezat access in VATS or diagnostic thoracotomy should be chosen so as to be consistent with the execution of definitive surgery at a later stage.
Surgical methods for staging. Cervical mediastinoskopiya is the main method for mediastinal staging in patients undergoing surgery.
In recent years, transesophageal ultrasound puncture biopsy (EUS-NA) and endobronchial ultrasound biopsy (EBUS-NA) of mediastinal lymph nodes are alternative methods with high sensitivity and accuracy in some centers.
Laparoscopy is recommended by some authors to exclude the direct involvement of the abdominal part of the diaphragm in a strict selection of patients for surgical treatment.
Staging system. Several staging system for the disease, which product includes the following elements: presence or absence of invasion of the adjacent chest wall, diaphragm, or mediastinal structures, involvement of mediastinal lymph nodes and presence with distant metastases (in Brigham, IMIG, UICC, BWH, etc.).. Today staging system for IASLC (International Association for the Study of lung cancer) [2] is well established in clinical practice.
T - primary tumor
T1a - covered ipsilateral parietal pleura;
T1b - covered and visceral pleura;
T2 - covered and lung, diaphragm;
CA - limited coverage of the chest wall, fascia endothoracica, netransmuralno covered pericardium;
T4 - involved bone, peritoneum, myocardium, mediastinum, pericardium transmural covered.
N - Regional lymph nodes
NX - Absent regional lymph nodes;
N0 - without metal in the regional lymph nodes;
N1 - meta in ipsilateral bronchopulmonary and hilar lymph nodes;
N2 - meta in subkarinalni or ipsilateral mediastinal lymph nodes, incl. ipsilateral about a. mammaria interna and peridiafragmeni nodes;
N3 - meta in the contralateral mediastinal lymph nodes, incl. contralateral about a. mammaria interna, ipsilateral and contralateral lymph nodes supraklavikularni.
M - metastasis
MO - no distance dedicated metal;
M1 - distance dedicated meta.
Stage of cancer I
T1
N0
MO
Stage Ia
T1a
N0
MO
Stage lb
T1b
No
MO
Stage II
T2
N0
MO
Stage III
T1, T2
N1
MO
T1, T2
N2
MO
CA
N0, N1, N2
MO
Stage IV
T
each N
MO
each T
N3
MO
each T
each N
M1
Treatment. After the diagnosis and clinical staging discuss therapeutic options for patients. Selections are made based on the stage and histological variant (nesarkomatozen version) of mesothelioma, as well as cardio-respiratory reserves and accompanying diseases of the patient. There are several surgical operations, administered alone or in combination with radiotherapy and chemotherapy (multimodal therapy). These include ekstraplevralnata pulmonektomiya (EuP), radical or palliative plevrektomiya and decortication (P / D), VATS talc pleurodesis or talc slurry [1, 3].
Limiting factor in the choice of therapy is the patient's ability to cope with their normal daily needs.
Patients under the age of 75, which are fixed and can not cope with the usual requirements, are suitable for EPE.
Patients in poor general condition and with impaired lung function is suitable for P / E. This surgery could lead to tumor reduction, providing the opportunity to better expand the lungs and improve the functional reserve.
Patients who can not serve themselves without a companion, not suitable even for P / E. Best supportive care in them remains VATS talc pleurodesis.
Surgical methods. surgical treatment 1) provide palliation to relieve stuffiness, 2) cytoreduction to increase the efficacy of other therapeutic methods, 3) radical removal when you need to achieve complete macroscopic resection with histologically clear resection lines (R0).
Ekstraplevralnata pulmonektomiya (EuP) includes en bloc resection of the lung, pleura, ipsilateral Hemeid-afragma and pericardium, the most closely corresponds to the principle of radicality (Fig. 3). Pericardium and diaphragm are recovered with fabric sails, preferably 1-2 mm Gore-Tex mesh (Fig. 4). The operation is most often performed by a rear-laterally thoracotomy as difficulty in handling of the diaphragm over the same skin incision may be entered further into the chest cavity several intercostal lower. Few authors consider that the use of longitudinal sternotomy prevail in these cases. EPP is a large-volume operation for 4-8% perioperative mortality and morbidity 50-65%, most commonly cardiac complications [4].
Radical P / D is possible in the early stages of the disease in still intact lung. With the removal of the parietal, visceral, mediastinal (and pericardium) and diaphragm pleura (together with the diaphragm) is achieved by the removal of the affected tissue mesothelioma (Figure 5). Extreme caution should be paid to dissect the pleural fissures [3]. Achieving complete resection is rarely possible due to the frequency of local recurrence appears to be very high. The operation is a difficult technical implementation, however, the incidence of mortality periopertivnata is less than 2%.
In most cases, D / P is compassionate and ability to relax. It may be effected except by thoracotomy through VATS with equal success. VATS talc pleurodesis is appropriate in patients who could not tolerate operating cytoreduction and in which lung can expand to such an extent as to provide intimate contact between Both pleura. The procedure is performed under local anesthesia with sedation of patients and therefore require no additional preoperative evaluation unless routine biochemical tests, ECG, X-ray and CT.
Radiotherapy. apply in adjuvant plan or for palliation of symptoms (with doses above 40 Gy). Radiotherapy after P / E presents very high risk of post-radiation pneumonitis, which is why lately preferred intensity-modulating radiotherapy (IMRT) and photon-electron therapy. Applying certain threshold doses is determined by the sensitivity of adjacent normal organs (heart, liver). Doses after EPP typically range between 50-54 Gy, with them to make good regional control [1, 3].
Chemotherapy. chemotherapy alone can not achieve radical cure [5]. In the neoadjuvant and palliative aspect has been studied many medications and schedules. As monohimioterapiya are best studied anthracyclines (Doxorubicin, Epirubicin) and platinum analogues (Cisplatin, Carboplatin).
Combination chemotherapy with Cisplatin 75 mg / m 2-1 and Pemetrexed (ALIMTA) 500 mg / m 2 - 1 iitravenozno applied in recent years with improved survival [5].
Hyperthermic intraoperative chemotherapy (HIOC). effectiveness of this new strategy was demonstrated in the treatment of malignant diseases of the abdominal organs, including. peritoneal mesothelioma. Hyperthermic therapy with high local levels of the chemotherapeutic provides maximum cytotoxic effect with minimal systemic side effects. [6]
Multimodal therapy. Includes neoadjuvant chemotherapy (3 courses), EPP and postoperative radiotherapy with a total dose of 54 Gy. In recent years it has been the method of choice because it leads to an increase in disease-free interval and improve overall survival. Some authors add intrapleural and intraperitoneal hyperthermic chemotherapy as prophylaxis of local recurrence. In patients with epithelial mesothelioma, mediastinal lymph node negative and resection lines in pure ekstraplevralnata pulmonektomiya achieved increase in average survival time of 52 months. [1]
New therapeutic methods. Anti-angiogenesis therapy (Thalidomide, SU5416, Bevacuzumab), photodynamic therapy and immunotherapy (y-interferon, Cytokine 1l-2, etc..) are new therapeutic approaches have yet to be validated [1]. Genetic studies on the characteristics of the gene expression in malignant mesothelioma, not only would help to individualize and optimization of treatment depending on the genetic analysis, but would allow the use of less invasive procedures with greater specificity and sensitivity. In this regard, treatment strategies are constantly changing, seeking to take advantage of advances in molecular genetic studies.
Weather. herd status of mediastinal lymph nodes and the absence of chest pain early in the disease are significant prognostic factors. The type of surgery (EPE, radical or palliative P / E), the presence or absence of positive resection lines and histology (epithelial or biphasic) also affect the prognosis without statistically significant [1, 3]. The surgical treatment of malignant mesothelioma is still controversial. The results of palliative P / E are very similar to those of EPE. This makes it very difficult to determine indicators on which to determine the choice of surgery to achieve optimal cytoreduction. In this way it can be ensured the survival of about months, is still not clear what is the quality of life of the operated during this time.
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