Malignant mesothelioma, MPM is a derived from pleural mesothelial cells, mainly to local invasion, high grade rare disease.
1. Etiology and epidemiology
MPM is the most common cause of exposure to asbestos; also infected with TB, the Ganges simian virus 40, contact nitrosamines, glass fibers, radiation, oxygen thorium, zeolite, beryllium, and hydrocyanic acid, and lipid aspiration pneumonia, may be as a risk factor, causing human genetic mutations or deletions, leading to occurrence of MPM; another study said MPM may be a family of autosomal dominant genetic disease. Zhongshan Hospital of Dalian University of Cardiothoracic Surgery, ZHAO Zhi
Australia, the world's highest incidence of MPM, 20 million people over the age is 3.54/10. Around the incidence of MPM is very large, ~ 0.6/10 0.1/10 million million, the overall upward trend. Among them, the most high Dayao County of Yunnan Province, the incidence rate of 8.5/10 million per year (1977 to 1983), 17.75/10 million (1987 ~ 1995). Male to female ratio, of 2:1 ~ 3:1, 6:1 in Australia.
Incidence of asbestos exposure to MPM the first time, usually 20 to 65 years. In the nineties of last century, European and American developed countries banned the production and use of asbestos, the incidence of MPM is expected to peak around 2020. China's industrial development and labor protection lagging behind, still the use of asbestos, the incidence of MPM will continue to grow in a very long time.
2. Diagnosis
The majority of our region, MPM incidence rate is very low, while the lack of specific symptoms and signs, the high rate of misdiagnosis of the disease, up to 83.3% [2]. From the onset of symptoms to diagnosis MPM, about two or three months, 25% of patients 6 months after the onset of symptoms the diagnosis [3]. Therefore, clinicians should be better understanding of the disease.
Patients may be asymptomatic or only early performance of shortness of breath after exercise, with the lesions progress to a cough, shortness of breath, persistent chest pain. Terminally ill, there may be difficulty in breathing, chest deformity, cardiac arrhythmia, cardiac tamponade, and even abdominal mass and ascites, or with intestinal obstruction and other performance; 60% to 95% of the patients had pleural effusion, can be found at any stage, in particular, is the epithelial type; mostly bloody pleural effusion, a small number of grass yellow exudate, may, rich in hyaluronic acid, which was sticky, exhausted after the rapid regeneration [1, 4].
MPM is a major feature of local invasion, along the fine-needle aspiration, thoracoscopy, or surgical incision site metastasis, the incidence of 2% -51%. Autopsy found that 54% -82% of pleural metastasis, but often without any clinical symptoms, and rarely a cause of death. The most common peritoneal metastasis of liver, adrenal gland, kidney, brain metastasis occurred 3%, and more common in sarcomas of [1].
X ray and CT examination of the non-specific manifestations of pleural effusion, rib destruction, costophrenic angle blunting, widened mediastinum, the heart increases so film. Specific performance are: ① nodular pleural thickening, the general thickness of 5 ~ 15mm, sometimes up to 25mm, or pleural effusion due to cover the show is unclear; ② fissure pleural thickening; ③ limitations of mass; ④ ipsilateral chest volume reduction, if there is pleural effusion, can offset this performance [1, 4]. There are also manifested as solitary pulmonary lesions [5] or pulmonary distribution of sizes of spherical masses [6].
Pleural disease is the most valuable CT screening method. It is noteworthy that 20% of mesothelioma patients showed calcified pleural plaques, easily misdiagnosed as benign disease [1].
In the identification of liquid and non liquid lesions, when the trace effusion and pleural thickening, B-ultrasound has advantages over CT, and dynamic observation of pathological changes with the respiratory movement. Because of the high resolution of soft tissue, in particular, are particularly sensitive to the subpleural fat, MRI can identify the basement with pleural nodules or localized soft tissue fluid, in MPM diagnosis, staging and treatment evaluation, the high value of [1 ].
PET / CT can be used: ① benign and malignant pleural mesothelioma identification, especially in the history of asbestos exposure and pleural thickening in patients with diffuse; ② MPM staging; ③ pleural effusion, but CT and MRI examination was abnormal cases; ④ evaluation of tumor response to therapy [1, 7].
Pleural fluid cytology in the diagnosis rate is low; positioning organizations to increase under the fine-needle aspiration diagnosis [1, 4].
Surgical diagnostic methods including diagnostic thoracoscopy, surgical thoracoscopy, thoracotomy biopsy, mediastinoscopy, surgery, etc., have high sensitivity and specificity, which can impose thoracoscopy surgery treatment, such as control of pleural effusion, pleural decortication, etc. [1, 8].
In general, MPM is divided into localized and diffuse type; histologic classification, including epithelioid, sarcomatoid and biphasic three categories [1]. Light microscope, the epithelial and poorly differentiated adenocarcinoma pleural mesothelioma is difficult to identify, and sometimes requires the use of immunohistochemistry. CEA, CD15 expression in adenocarcinoma often, but not normally expressed in MPM, epithelial membrane antigen expression in MPM cell membrane, cytoplasm in cancer expression. In addition, CK5, CK6 retinal protein and calcium are more specific for MPM. When ambiguous immunohistochemical results, you can use electron microscopy - the gold standard for diagnosis, MPM has a long and branched microvilli, desmosomes and more tension wire [9].
Recently, we have a case of treatment in patients with epithelial MPM. The number of biopsy pathology expert consultation, some experts diagnosed as poorly differentiated adenocarcinoma, followed by immunohistochemical staining, calcium retinal protein (+), vimentin (+), CEA (-), thyroid transcription factor -1 (-), CD68 (+), the results support the diagnosis of MPM. Interestingly, three serum CEA examination before surgery, the patient has two highly expressed in tumor tissue but not expressed. This reflects the biological diversity of MPM.
At least five MPM staging system was born, is more reference to the 1995 International TNM staging group developed mesothelioma system, but compared with the staging of lung cancer, yet not fully reflect the survival rate of pathological and biological true character, but also influence the choice of treatment and efficacy evaluation.
3. The treatment of MPM
Without treatment, MPM patients, median survival time (MST) only a few months, most patients died of local tumor invasion. Treatment, and achieved good local control is the key to long-term survival. Surgery is the only possible means to achieve radical effect. However, a clear diagnosis for the small number of surgery [1, 4, 8, 9]. The absence of large randomized studies have been unable to confirm the maturity of the treatment model. MPM treatment mainly around two aspects of surgical and non surgical.
1) Surgical treatment of multi-disciplinary
Surgical methods are commonly used extrapleural pneumonectomy (EPP) and pleural decortication. EPP for the en bloc hemi pleura, diaphragm, pericardium and lungs, and its 2-year and 5-year survival rates were 30% to 40% and 5% to 15% [10, 11]; and significantly prolonged disease-free survival [11, 12]. Today, EPP mortality rate from 30%, has dropped 3.4% to 8%, but there are more than 50% incidence of postoperative complications, there is a big risk, highly skilled doctors can make more secure EPP [8, 13, 16].
For the localized MPM, pleural decortication also can obtain good results, and operative mortality and complication rates lower than the EPP [11]. For some early patients, video-assisted thoracoscopic decortication the pleura also showed better efficacy [17]. Compared with pleural decortication, EPP is more suitable for hemi-thorax after radiation therapy to strengthen, for the control of tumor recurrence seems to be more effective.
Including 945 patients a retrospective study: surgery can improve survival, surgical multidisciplinary treatment of patients median survival was 20.1 months. While increasing efficacy, EPP hemi-thoracic surgery plus radiotherapy, no increase in procedure-related concurrent [18].
A multi-center study: gemcitabine, cisplatin chemotherapy underwent three EPP, after chest radiotherapy, MST of 23 months [19]. Another 8 cases of MPM III or IV patients, four of gemcitabine and cisplatin chemotherapy underwent EPP, re-hemi-thoracic radiation therapy (54 cGy), MST 33.5 months [20]. Gemcitabine and carboplatin neoadjuvant chemotherapy I to III of MPM patients, re-operation and hemi thoracic radiotherapy EPP, but also achieve similar results [21]. Tip of the treatment model may be standard treatment for MPM.
After surgery, N2 lymph node recurrence of MPM patients faster, it seems appropriate surgical treatment [12]. The choice of surgical approach to the disease need to consider the scope of accompanying diseases, such as multi-disciplinary treatment modalities can only gain a better local control.
2) Non-surgical multidisciplinary treatment
Loss of timing of surgery patients can be chemotherapy, radiation therapy, and cytokines and other biological treatments.
Overall, MPM chemotherapy is not satisfactory, single drug or drug combination MST treatment of patients 13 to 17 months, efficiency <20% [22, 27].
A 1965 to 2001 based on the results of meta-analysis study showed that cisplatin is the most effective drugs, combination therapy can increase the response rate, but does not prolong survival [22].
Recent researches focus on gemcitabine, vinorelbine, pemetrexed less side effects such as drugs, as well as in combination with cisplatin. A group of patients with previous chemotherapy, the pemetrexed and cisplatin treatment, tumor response rate of 32.5%, 68.7% remission rate [23]. Although pemetrexed monotherapy with gemcitabine have shown a certain effect, but the two combined treatment MPM, compared with pemetrexed and cisplatin results slightly worse, MST was 8.08 months and 10.12 months [24] . Pemetrexed and carboplatin slightly worse than the efficacy of cisplatin, but a lower incidence of toxicity [25]. The MPM patients treated by gemcitabine plus vinorelbine treatment, remission rate was 43.3%, MST was 10.9 months [26]. Recently, two multicenter randomized controlled study of disappointing results, compared to best supportive care, vinorelbine combined with pemetrexed or best supportive care did not significantly prolong survival [27, 28]. Is clear that these drugs get a certain rate of tumor control and symptom relief; but the value of platinum drugs still can not be ignored.
Treatment when, MPM were mostly in the late extensive tumor growth, and adjacent to the heart and lungs and other vital organs, leading to the limitations of radiation field and dose, thus affecting the radiation effect.
Basic research and on the drainage port puncture or incision of the prophylactic irradiation of the study: sensitive to radiotherapy of malignant pleural mesothelioma [29]. Studies have shown [30-32], a single dose ≥ 4Gy, total dose of ≥ 40Gy, can reduce the local symptoms; but there are the opposite conclusion [33].
The only systematic review of the effects of radiation therapy shows: the lack of randomized controlled studies have shown that radiation therapy can cure or prolong the life of MPM patients; in improving the quality of life and symptom control, the role of radiation therapy are very limited [34]. However, the new technology carried out indicates that a glimmer of hope.
Conformal radiotherapy target volume can increase access to higher dose, and reduce the radiation dose of surrounding normal tissue. A group of 7 cases of MPM patients underwent radical surgery enhanced radiotherapy, despite the 6 cases of stage Ⅲ disease, but no case of local recurrence, and no serious complications [35].
Recently, a phase Ⅰ clinical trials have shown that pleural cavity injection of IFN-beta gene transfer of adenovirus to induce a certain cellular and humoral immune response and partial tumor regression [36].
In addition, the effect of protease inhibitors still need clinically proven [37]. The source of oral platelet growth factor receptor inhibitors and epidermal growth factor receptor tyrosine kinase inhibitor efficacy was disappointing [38, 39]. Pleural decortication, the use of multi-hematoporphyrin photosensitization mediated eradication of residual MPM cell therapy, Matzi so verify its safety, and some effect, but the sample size should be expanded [40].
4. Localized MPM
Localized MPM is extremely rare, and more than 1% [1]. A group of 218 cases of MPM in 10 patients with localized disease, its biological behavior and diffuse MPM there are differences. However, the epithelial type, type and bipolar sarcoma was limited to the growth of MPM can be. Including the chest wall and lung invasion and partial resection can achieve better results, but EPP is not required [5, 41].
In untreated cases, one case of women, limited type, epithelial type MPM patients survived for more than 12 years [42]. This seems to prove that women, epithelial type, limitations of MPM there is a link with a good prognosis [1]. But histology, immunophenotype and ultrastructural studies have shown the limitations of good prognosis diffuse type MPM MPM with no significant difference between the localized type is difficult to predict the biological behavior of MPM [43].
Recently, we have clinics one case MPM, for women, epithelial type, tumor limited the growth of the pleural effusion can grow fast, tumor blood supply is rich in local radical resection, although the line of intrapleural injection pemetrexed, gemcitabine and carboplatin chemotherapy, However, short-term disease recurrence, and rapid progress, only to survive for 6 months. That can be highly localized MPM malignant biological behavior.
5. Outlook
At present, few studies for the MPM, a case of less is in. Moreover, the disease is the lack of attention. The implementation of MPM patients in developed countries up, every 2-3 years, held a special forum for the disease, the participants, including thoracic surgery, radiology, oncology internal medicine, and large medical company personnel, the discussion covers all aspects of the disease [44] . Understanding and control of these measures on MPM very helpful.
