Pleural mesothelioma is a pleural tumor originating from pleural mesothelial cells, benign is less common, malignant pleural mesothelioma is more common. Early diagnosis is difficult and prognosis is poor. 80% of occurrences are associated with exposure to asbestos, and other causative factors may include infection with simian virus, nonspecific industrial compound exposure, and genetics. Because asbestos is still widely used, the incidence is predicted to continue to increase and to peak in the next 10 years. There is still a lack of effective methods of treatment and the median survival time is only 4-12 months. The diagnosis and treatment of pleural mesothelioma has become another medical problem that we need to face after lung cancer and needs to be given more attention and focus. Jin Minghua, Department of Thoracic Surgery, Shandong Provincial Chest Hospital
1. Diagnosis of pleural mesothelioma
Improving the diagnosis rate, especially the early diagnosis rate, is of great value to improve its prognosis. In recent years, a lot of discussions have been made on this. The clinical manifestations of pleural mesothelioma vary, the main clinical manifestations are pleural effusion (about 60%) and chest pain (about 60%); systemic symptoms include weight loss, malaise, etc. <30% of those with systemic symptoms at diagnosis usually appear in the late stage of the disease, and <10% of those without symptoms. Common signs include pleural effusion-related signs (turbid percussion, decreased breath sounds, etc.), thoracic fixation, decreased breath sounds or bronchial breath sounds, mortar and pestle fingers (less frequently), and signs of local invasion (superior vena cava obstruction syndrome, nerve or esophageal compression, etc.). These clinical manifestations are not highly specific for the diagnosis and are easily confused with pleural metastases, encapsulated pleural effusion and peripheral lung cancer, which are easily misdiagnosed in clinical practice.
1.1 Imaging diagnosis
Imaging examination plays an important role in the diagnosis of pleural mesothelioma. Although the diagnostic sensitivity and specificity of X-ray chest film are low, it is still the most basic means of diagnosis. Pleural mesothelioma should be considered when the lesion has linear manifestations of pleural thickening, nodules or masses, localized osteolytic destruction of ribs and a large amount of pleural effusion. CT of the chest is significantly superior to X-ray chest radiographs in evaluating the extent and degree of invasion and its efficacy, and can also guide puncture; the vascular flow-space effect, multiplanar imaging capability and good soft tissue resolution of magnetic resonance imaging make it superior to CT in demonstrating horizontal interlobular pleura, diaphragmatic pleura and subdiaphragmatic peritoneal involvement, but inferior to CT in detecting intra-tumor calcification and rib destruction. positron emission tomography can identify mediastinal lymph node metastases and distant unknown metastases, which is very helpful for staging and treatment planning, and has good application prospects in diagnosis.
1.2 Histological diagnosis
Pleural biopsy and pleural effusion cytology are easy to perform, but the positive rate is not high. In contrast, television thoracoscopic biopsy and surgical open-chest biopsy have a high positive rate, especially television thoracoscopic biopsy, which can not only visualize the entire thoracic cavity, directly observe the size and distribution of lesions and the invasion of adjacent organs, and obtain sufficient biopsy specimens under direct vision, but also is relatively easy to operate, less traumatic, and easily accepted by patients, so it is the best means to diagnose pleural mesothelioma at present. The diagnostic rate of thoracentesis alone is 26%, the positive rate of pleural biopsy combined with pleural effusion cytology is up to 39%, and the diagnostic rate of thoracoscopic biopsy can reach 98%.
1.3 Screening of markers
Many patients are already in advanced stage when they are diagnosed, so researchers try to screen for markers with convenient detection, good specificity and high sensitivity from blood and plasma cavity effusion, among which soluble mesothelial-related protein and bone bridge protein are more studied. It is a promising early diagnostic indicator.
1.4 Exploration of gene chip-based diagnostic methods
The rapid development of molecular biology technology has made it possible to analyze the changes of gene expression profiles during the occurrence and development of tumors by gene microarray technology with high throughput and high parallelism, and many studies have been conducted recently to explore new methods of gene microarray-based diagnosis. Although gene microarray-based diagnosis is still in the research stage, it has shown good application prospects.
1.5, Typing
Pleural mesothelioma is usually classified into limited and diffuse types according to the growth pattern and gross morphology, with limited types being mostly benign and a few being low-grade malignant, and diffuse types originating from the pleura itself, which are almost always highly malignant. There are usually four tissue types: (1) epithelial type, accounting for about 40%, often accompanied by pleural effusion and has a good prognosis; (2) sarcomatous type, accounting for about 20%, usually not accompanied by pleural effusion and has the worst prognosis; (3) mixed type, accounting for about 35%; (4) connective tissue hyperplasia type, the least, accounting for about 5%.
1.6, Staging
In order to predict patient prognosis and guide treatment, researchers have tried various staging methods. In 1990, the International Union Against Cancer (IUAC) proposed a staging method based on the applicable staging of other tumors, and in 1994, the International Society for Mesothelioma (ISM) empirically improved on this basis to provide a more detailed scientific description of staging and to evaluate staging in conjunction with the long-term prognosis and survival of patients. in 2002, this staging system was adopted by the IUAC and the American Cancer Society and used in In 2002, this staging system was adopted by the International Union Against Cancer and the American Cancer Society and used in prospective clinical trials to evaluate new therapeutic measures. Although it is essential to evaluate patients by imaging, the correct staging can only be determined by surgery for most patients.
2. Current status and progress in treatment
Although there are various methods of treatment for pleural mesothelioma, such as surgery, radiation therapy, chemotherapy, and immunotherapy, there is no evidence so far to show which method is better. The existing traditional treatment methods can only improve the quality of survival and prolong the survival period to a limited extent, however, in recent years, multidisciplinary comprehensive treatment has shown encouraging results, and some new treatment methods are being studied in depth, bringing new hope to the treatment of pleural mesothelioma.
2.1 Surgery and radiation therapy
The purpose of surgery is to remove the tumor to relieve respiratory distress and to increase the efficacy of adjuvant therapeutic measures. Total extrapleural pneumonectomy and partial pleurodesis are the two most commonly used surgical methods. The former requires complete resection of the affected mural and visceral pleura, lung, as well as the diaphragm and part of the pericardium, which is highly invasive and has a high perioperative mortality rate. The latter requires the removal (stripping) of all of the visceral and mural pleura as much as possible while preserving the lung tissue, which is relatively less traumatic and is widely used in clinical practice. The median survival time is 13 months.
The main purposes of radiation therapy for pleural mesothelioma are: prophylactic radiation therapy to avoid tumor cell implantation and metastasis during thoracoscopy or chest drain removal; symptom relief; and post-surgical adjuvant therapy as part of comprehensive treatment. The protection of surrounding vital organs such as heart, lung, esophagus, and spinal cord should be fully considered when performing chest radiotherapy, which increases the difficulty of giving sufficient radiation dose while avoiding serious complications. For early stage patients, high-dose chest radiotherapy after complete surgical treatment can reduce the local recurrence rate and prolong survival time.
2.2 Chemotherapy
The main purpose of chemotherapy is to increase overall survival, improve quality of life and relieve tumor symptoms. At present, only a few chemotherapy drugs have achieved good efficacy.
2.2.1 Combined chemotherapy with cisplatin and anti-folate agents
The combination of cisplatin with anti-folate agents (pemetrexed, raltitrexed) has achieved better results than previous chemotherapy regimens and has become an important research development in chemotherapy.
2.2.2 Single-agent chemotherapy
Numerous non-randomized trials have shown that conventional single-agent chemotherapy is less effective. Adriamycin is the most studied single agent in chemotherapy, but its therapeutic response rate is only 15% with a median survival time of 7-13 months, while other single agent chemotherapy such as carboplatin, cyclophosphamide, isocyclophosphamide, and paclitaxel have an average therapeutic response rate of 10%-20%. New chemotherapeutic agents that have emerged in recent years such as liposomal anthracycline, gemcitabine and pemetrexed also have unsatisfactory efficacy as single agents. Pemetrexed is a multi-targeted folate inhibitor that works by inhibiting a variety of folate-dependent enzymes, with an overall response rate of only 14% when applied alone.
2.2.3 Combination chemotherapy
Most combination chemotherapy regimens are based on anthracycline antibiotics or platinum-based drugs, and most of these regimens have a response rate of less than 20% with a median survival of 6 to 12 months.
2.3 Molecular targeted therapy
Molecularly targeted therapy has made an important breakthrough in non-small cell lung cancer, and it is hoped that molecularly targeted therapy will also bring light. Although a variety of targeted drug therapies have been tried in the study, the results have not been satisfactory, and the clinical feasibility of molecular targeted therapy is pending more in-depth study.
2.4 Immunotherapy and gene therapy
Immunotherapy and gene therapy are used to induce disorders of cellular and humoral immune responses, thus affecting the anti-tumor immune response. The current immunotherapy is usually systemic or topical administration of interferon or interleukin in the chest, but the clinical results are reported to be inconsistent. Local treatment can inhibit the production and promote the absorption of pleural effusion, reduce the production of encapsulated effusion, and improve the quality of survival of patients. Thoracic infusion thermochemotherapy is often used. Thermochemotherapy is the integrated application of heat and chemotherapy, using the biological effect of heat to kill tumor cells and enhance the anti-tumor effect of chemotherapy drugs, and the two play a synergistic anti-tumor effect. Currently, the effect of local treatment is reported inconsistently, and more in-depth research is needed.
3.Conclusion and outlook
Pleural mesothelioma is highly malignant, progresses rapidly, and still lacks effective treatment, but its incidence is still increasing and is expected to reach its peak in 2010-2020, which presents us with new challenges, such as can the role of surgery be confirmed by randomized trials? Will the role of radiotherapy in the treatment be confirmed in the future? Pemetrexed and cisplatin combination chemotherapy has improved treatment response rates and made great progress, but are there better combination chemotherapy regimens? What are the feasibility and clinical prospects of immunotherapy, gene therapy and targeted therapy? Many questions need to be studied in greater depth. Although there is still a lack of evidence-based medical evidence, it can be predicted that a multidisciplinary and comprehensive treatment model will be the direction of research for pleural mesothelioma in the future. In the next 2-3 years, the large international clinical trials currently underway are expected to provide useful information for the treatment of pleural mesothelioma and are worthy of our expectation.