Introduction
Diffuse pleural mesothelioma used to be calledMalignant mesotheliomaIt is a slow-lethal tumor, although the incidence is not high, but it is more common than localized pleural mesothelioma, which is the most common type of pleural primary tumor. Clinical manifestations are associated with invasive behavior, which usually locally invades the pleural cavity and surrounding structures. If left untreated, the median survival is 4 to 12 months.
the reason
In the early stage of malignant mesothelioma, there are many white or gray particles and nodules or thin plates on the normal or opaque visceral or parietal pleura. As the tumor develops, the pleural surface becomes thicker and thicker. Nodules, tumor nodules extend to the square, continuous into a piece, encapsulation of the lungs so that the sputum shrinks smaller and the affected side of the chest wall collapses. In the advanced stage, the tumor may involve the diaphragm, the intercostal muscle, the mediastinum, the pericardium, and the contralateral pleura. 50% of autopsy patients have found blood-borne metastases, but few are mentioned clinically.
There are two pathological anatomical types of malignant mesothelioma:
1 single fibrous pleural mesothelioma. From the visceral pleural growth, plate or meat stem, the clinical symptoms caused by the tumor are due to their expansion and development, and the intrathoracic structure is squeezed to displace it. If it can be diagnosed early, it can be treated surgically.
2 widely spread mesothelioma. This type invades the lobe, infiltrates the diaphragm and intercostal muscles, and can affect the pericardium and large blood vessels through the mediastinal pleura.
The microscopic findings of malignant mesothelioma have the characteristic that there are various distinct tissue components in a single tumor nodule or a tumor nodule with the same appearance as the naked eye. The histopathological classification of malignant ecdysoma is epithelial, fibrous (interstitial) and mixed. The epithelium of epithelial tumor cells has various structures, such as papillary, tubular, papillary, and banded sheets. Polygonal epithelial cells have many long, slender, branched microvilli on the surface, desmosomes, bundled elastic filaments and intercellular compartments. Fibrous cells are similar to spindles, have an equal configuration, have egg-shaped or slender nuclei, and have good nucleoli development. The hybrid type has both epithelial and fibrous structures. When taking a biopsy from a tumor mass, the more specimens are taken from different parts, the more it looks like a hybrid.
symptom
Malignant pleural mesothelioma patients are more male than female (2:1). Most patients are between 40 and 70 years old. The average age of foreign patients is 60 years old, and China is only 45.2 years old. The first symptoms were chest pain, cough and shortness of breath. About 10.2% of patients had fever and sweating, and 3.2% of patients had joint pain. Due to the involvement of the diaphragm, chest pain can be transmitted to the upper abdomen and the affected shoulder. About 50% to 60% of patients have a large amount of pleural effusion with severe shortness of breath, of which bloody pleural effusion accounts for 3/4. Patients with no large pleural effusion have more severe chest pain. Weight loss is common. Some patients have periodic hypoglycemia and hypertrophic pulmonary osteoarthropathy, but these indications are more common in benign mesothelioma.
Epithelial and mixed pleural mesothelioma are often accompanied by a large amount of pleural fluid, while the fibrous type usually has little or no pleural fluid. Epithelial patients seem to have more involvement of the supraclavicular or axillary lymph nodes and extend to the pericardium, the contralateral pleura and peritoneum; fibrous type with distant metastasis and bone metastasis.
Radiological indications: Common chest X-rays found pleural effusions, often accounting for 50% of one side of the chest. The ipsilateral lung was wrapped by tumor tissue, the mediastinum moved to the side of the tumor, and the thoracic cavity of the affected side became smaller. The chest radiograph was not widened in the late stage, and the pericardial exudate enlarged the heart shadow, showing soft tissue shadow and rib destruction.
The pleural disease on X-ray conventional chest radiographs can be masked by pleural effusion. For patients with suspected malignant pleural stromal tumors, CT is most useful. CT can show pleural thickening with irregular nodular inner edge. Malignant pleural mesothelioma was identified from other pleural thickening lesions. Due to fibrous tissue and tumor tissue and pleural effusion, the main interpulmonary fissure is markedly thickened. For tumor invasion, interpulmonary fissure may be nodular. Usually, CT can detect the degree of nodules in the lungs and the extent to which the lungs are shrunk by the tumor capsules and the collapse of the chest wall.
Pleural effusion: Mesothelioma combined with pleural effusion is exudate, 50% is serum bloody fluid. If the tumor is large, the blood sugar level and pH in the pleural effusion may be reduced, and the pleural effusion is thicker due to the large amount of clear acid (>0.8 mg/ml). The pleural effusion generally contains normal mesothelial cells, differentiated or undifferentiated malignant mesothelial cells, and varying amounts of lymphocytes and polynuclear leukocytes. A cytological examination of the pleural effusion helps to make a diagnosis.
Routine laboratory tests: found during the onset of illnessThrombocytopeniaIndividually reported platelets up to 1000 × 109 / L, serum carcinoembryonic antigen in some patients increased, serum immunoelectrophoresis phenomenon IgG, IgA or IgM increased, the cause is not good, serum fetal protein is generally normal.
diagnosis
Patients with exudative pleural effusion, especially those with a history of exposure to asbestos, should consider the diagnosis of malignant pleural mesothelioma. Chest CT can determine the diagnosis, chest CT can determine whether pleural calcification or bone structure is damaged. When the tumor invades the diaphragm and chest wall, the magnetic resonance imaging is better than CT. Although pleural effusion, thoracic pleural biopsy, and pleural effusion cell sections can be used for malignant diagnosis, pleural metastatic adenocarcinoma and malignant mesothelial fistula cannot be identified.
If three technologies have been developed in the past 10 years, it is certainly helpful to diagnose malignant mesothelioma. These three techniques were histochemical staining with periodic acid-Schiff's solution, with keratin and carcinoembryonic antigens as immunoperoxidase assays and electron microscopy. For these tests, biopsy specimens must be fixed immediately with neutral Fleming fluid, and another small tumor biopsy specimen is destined for use in glutaraldehyde fluid for electron microscopy.
Periodate-Schiff staining (PAS) is the only reliable histochemical method for distinguishing malignant pleural mesothelioma from adenocarcinoma. Although the characteristics of various metastatic adenocarcinomas are different, they are strongly positive after amylase digestion. Vacuation can be diagnosed as adenocarcinoma rather than malignant pleural mesothelioma.
The immunoperoxidase technique uses antibodies to keratin and carcinoembryonic antigen (CEA), which is also effective in distinguishing malignant pleural mesothelioma from metastatic adenocarcinoma. The carcinoembryonic antigen was stained with immunoperoxidase, and the staining of malignant pleural mesothelioma was generally light or not colored. In contrast, adenocarcinoma stains are moderate and very concentrated. In addition, the study of keratin with immunoperoxidase also showed a significant difference between mesothelioma and adenocarcinoma. At present, 8 markers have been found for identification: tumor with glycoprotein 72 (B72.3), Leu-Mi, Vimentin, thrombomodulin, mucin component, cancer antigen positive for 100% specificity and sensitivity of adenocarcinoma Sex. Since the carcinoembryonic antigen test often has a false negative, it is best to use two tumor markers, generally using CEA and B72.3. If the two are positive, the adenocarcinoma is 100% specific and 88% sensitive; if both are negative, it is 100% specific and 97% sensitive to mesothelioma.
Electron microscopy is also useful for identifying malignant pleural mesothelioma and pleural metastatic adenocarcinoma. Malignant pleural mesothelioma is distinguished from lung, breast cancer and adenocarcinoma of the upper gastrointestinal tract. The surface of the microvilli is fine and long, with branches, and the tension filament is rich, and there are no micro-villi small roots and pieces. Metastatic adenocarcinoma derived from the ovary and endometrium has intrinsic tissue deformation, including abundant mucin droplets, large amounts of cilia, and dense nuclear particles. These changes are absent in stromal tumors, and the villi of adenocarcinoma are short and Crude.
The pathological diagnosis of malignant pleural mesothelioma remains controversial. Although malignant mesothelioma is classified together with soft tissue sarcoma, only 20% of histology is purely sarcoma. 33% to 50% of malignant pleural mesothelioma is histologically epithelial or tubular and papillary, while the other 30% are epithelial and sarcoma mixed, most pathologists believe that only patients with sarcoma or mixed tissue can Diagnosed as malignant pleural mesothelioma. Based on special staining and electron microscopy data, experienced pathologists are also willing to diagnose malignant pleural mesothelioma in patients with epithelial type.
Identification
Although pleural effusion cell smears, thoracic pleural biopsy, and pleural effusion cell block biopsy can make a malignant diagnosis of cupping net, but can not identify pleural metastatic adenocarcinoma and malignant mesothelioma, the main sputum is through light microscopy, histochemistry, Immunohistochemistry, hyaluronic acid determination and other methods are differentiated from pleural metastatic adenocarcinoma.
complication
(1) pleural adhesion, pleural adhesion is the most common complication of this disease, because the patient will soon appear after pleural effusion, using chemical injection into the pleural cavity, causing pleural adhesion, most patients' pleural effusion is controlled, so If the pleurodesis fails or is in a patient who is planning a diagnostic thoracotomy, pleural stripping should be considered.
(2) Infection is the most common complication of tumor chemotherapy. It is characterized by rapid development of the disease. Once the infection occurs, it is easy to develop into sepsis. Because the infection occurs mostly after the leukopenia after chemotherapy, and the chemotherapy reaction is not fully recovered at this time, Sometimes the symptoms of the primary disease are even worse than the general sepsis, and these clinical features cause diagnostic difficulties. At this time, you may not wait for the test results, you can start treatment, it is best to use broad-spectrum antibiotics, and the dosage should be sufficient, but the course of treatment should not be too long. Do not use sulfa drugs or chloramphenicol. Pay close attention to mixed infections or double infections during treatment.
(3) malignant body cavity effusion malignant body cavity effusion can be the first symptom of malignant disease, but most patients with malignant effusion is a complication caused by tumor or metastases. Mainly manifested as pleural effusion, ascites and pericardial effusion. Malignant body cavity effusion may have little effect on quality of life at first, but if progress can lead to worsening of the disease and death, appropriate measures should be taken in time to promptly give palliative care. Diffuse peritoneal malignant mesothelioma is easy to be complicated with malignant ascites.
treatment
Western medicine treatment
Until today, there is no effective treatment for malignant pleural mesothelioma, but after a certain method of treatment, a small number of patients at home and abroad have lived for 5 years, the longest is 22 years, most people think that it may be related to the natural survival time of the tumor. It is related to the stage. According to Butchart staging, malignant pleural mesothelioma is divided into four phases.
According to clinical manifestations, stage I epithelial malignant pleural mesothelioma may have long-term survival, so it is recommended to perform radical pleural pneumonectomy for these patients. For cases of stage II, III and IV epithelial and other pathological types, whether treated or treated, radical or palliative surgery and the efficacy of chemotherapy and radiotherapy, the survival curve after treatment is basically the same, the average survival time is In 18 months, about 10% of cases survived for 3 years.
Table 1 Clinical stage of malignant pleural mesothelioma
Stage I tumors are confined to the parietal pleura, involving only the ipsilateral pleura, lung, pericardium, and mediastinum
Stage II tumors invade the chest wall or involve the mediastinum, the esophagus, heart, and contralateral pleura. Lymph node involvement only in the chest (N2)
Stage III tumors pass through the diaphragm and involve the peritoneum, invading the contralateral pleura and bilateral chest, involving the extrathoracic lymph nodes.
Long-term blood-borne bone metastasis
1. Palliative treatment of pleural effusion in patients with malignant pleural mesothelioma. It will appear soon after puncture and aspiration. Injecting chemicals into the pleural cavity, causing pleural adhesions. Most patients have pleural effusion control, so if pleurodesis fails or In patients with a diagnostic thoracotomy, pleural stripping should be considered.
Malignant pleural mesothelioma can be spread along the puncture, the channel of the thoracic duct and the open thoracic incision, but the subcutaneous deposits caused by the seldom cause symptoms, so there is no need to treat it. If the patient is treated, these subcutaneous nodules can also be used as Observe the indicators of efficacy.
Chest pain in patients with malignant pleural mesothelioma is the most difficult symptom to treat. It is particularly severe in the late stage. It persists throughout the day and does not respond to radiotherapy. It should be given enough sedative painkillers, including opioids to relieve pain, and the last moment of life. .
2, surgical treatment There are various surgical treatments for malignant pleural mesothelioma, the first is enlarged pleural pneumonectomy, which is the part of the chest wall, the whole lung, the diaphragm, the mediastinum and the pericardium. This procedure is only applicable to patients with stage I functional epithelial malignant pleural mesothelioma. Severe cardiopulmonary dysfunction is a contraindication to this procedure. A standard posterolateral thoracotomy in the fourth intercostal space, together with the tough and thickened parietal pleura and tumor nodules, bluntly stripped from the chest wall, this operation can cause extensive bleeding, oppression, electrocautery and suture Drain carefully and completely stop bleeding. The mediastinal pleura is then separated from the top of the hilum and the paratracheal lymph nodes are removed. In the front, at the tip of the lung, the internal mammary artery and vein are ligated, and all visible lymph nodes along with these blood vessels and pleura are removed from the anterior chest wall. Later, the lymph nodes of the esophageal and tracheal bulges are removed. Cut the happy bag from the corresponding part on the left side. At this point, it is decided to cut the lungs first or remove the diaphragm first. The order depends on the location of the tumor and the extent of its extension. Transect the hilar and blood vessels and bronchi, as in any pericardial (expanded) pneumonectomy. The lower part of the pleura is not as low as the diaphragm, and the diaphragm can be removed in the lower part of the pleura after the pleura. For adequate exposure, a second incision is generally made between the 8 to 10 ribs on the same side. Because of the intraoperative placement of the patient in the lateral position, after removal of the diaphragm, the liver tends to shift from the superior mediastinum, compressing the inferior vena cava, leading to heartbeat and blood flow disorders. After removal of the diaphragm, the defect can be repaired with Maxlex mesh or polysilicon material, and some people use the dura repair. Regardless of the use of any materials and techniques, it must be kept tight to prevent blood or pleural effusion from flowing into the abdominal cavity by the thoracic farmer; the continuous suture method should be used to firmly suture the residual edge of the diaphragm to make the abdominal organs unable to Invade or break into the chest. Before closing the chest, connect the chest tube to the suction of the suction device. The operative mortality rate of extended pleural pneumonectomy is 10% to 25%, but the effect is not better than pleural resection, so it is not recommended for widespread use.
The second surgical treatment is pleural resection, which is non-radical, because the tumor is often tired of the lungs below it. This surgery does not improve the survival time of patients with malignant pleural mesothelioma, but it seems to control pleural effusion and improve the quality of life of patients. In addition, chest pain caused by malignant pleural mesothelioma can sometimes be relieved after resection of the pleura. For cases suspected of malignant mesothelioma, a diagnostic thoracotomy should be considered for pleural resection. A large number of pleural effusions, as well as cases of chemical pleurodesis failure, may also be considered for pleural resection. From the above, pleural resection is a palliative operation, the purpose of which is to remove the parietal pleura and part of the visceral pleura to prevent recurrence of pleural effusion and reduce the symptoms of chest pain. Generally, the sixth intercostal space is used as the posterolateral incision for thoracotomy, the blunt or sharp free wall layer and part of the visceral pleura involved in the tumor are removed from the chest wall and the lungs respectively. This operation causes the spinal cord or arm nerve to be caused by heat conduction. The plexus is damaged. It is best to use a high-frequency argon knife when the tumor is removed at the side of the spine and at the top of the thoracic cavity. In particular, be careful to retain the nerves and blood vessels in the top of the chest and in the mediastinum, remove the tumor tissue as much as possible, reduce its volume, and facilitate postoperative radiotherapy and chemotherapy. After the operation, the thoracic closed drainage was used for negative pressure suction.
3, chemical treatment of anthracyclines is considered effective for malignant pleural mesothelioma, followed by cisplatin, mitomycin,CyclophosphamideFluorouracil,Methotrexate, vinca alkaloids, etc., currently used, anthracycline-based comprehensive chemotherapy. In recent years, statistics on doxorubicin-based chemotherapy at home and abroad have a total effective rate of about 20%, of which alkaloids (CAO) are better; the total effective rate of various treatments without anthracyclines It is 21%, of which mitomycin and cisplatin (MP) are preferred. Cisplatin increased the dose of methotrexate. Chemotherapy continues until the condition is not exacerbated.
4, radiotherapy external radiotherapy is very disappointing for malignant pleural mesothelioma, but extended extracorporeal radiotherapy is considered effective, can relieve chest pain and control pleural effusion in some cases, but has no effect on the disease itself. In vitro irradiation of more than 40Gy has a palliative effect, the response rate of 50 ~ 55Gy irradiation is 67%, a small number of patients survived for 5 years, but almost all patients still die of recurrence or metastasis.
Intracavitary radiotherapy has some response to a few malignant pleural mesothelioma, and a small number of patients with long-term efficacy, there seems to be a glimmer of hope. The main isotope is radioactive gold, which has affinity with cells covering the serosal cavity and is particularly suitable for the treatment of diffuse tumors such as mesothelioma. The main therapeutic effect is due to the radioactivity of the beta plasmid, which has a penetration of 2 to 3 mm, which is most effective for early tumors, but it is difficult to find cases of early malignant pleural mesothelioma. In the early years, the application of colloidal 198 gold into the pleural cavity, a few cases that have survived for 5 years, has been rarely used due to protection difficulties.
In the comprehensive treatment and surgery, the irradiation or isotope 132I, 192Ir, 32P implantation in the cavity and postoperative radiotherapy plus chemotherapy, no long-term cure.
5, comprehensive treatment in recent years, the use of comprehensive treatment measures, after pleural lung resection and CAP regimen chemotherapy (cyclophosphamide 600mg / m2, doxorubicin 60mg / m2, cisplatin 75600mg / m2, continuous use of 5 courses, each The interval between treatments is 3 weeks). After surgery, 55 Gy of external irradiation was performed at the site of the original tumor or the location of the residual tumor. Analysis of 53 patients who underwent comprehensive treatment had a perioperative complication rate of 17% and a operative mortality rate of 5.8%. The average survival time is 16 months (1 to 8 years). The 1-, 2-, and 3-year survival rates of 31 patients with epithelial type were 7%, 50%, and 2%, respectively. The 1- and 2-year survival rates of mixed and sarcoma patients were 45% and 7.5%. After 25 months. Patients with local mediastinal lymph node metastasis have shorter survival time than those without lymph node metastasis. Those with negative mediastinal lymph node metastasis have a 5-year survival rate of 45%, so early treatment is very important.
prevention
The prognosis of this disease is extremely poor, and there is currently no effective treatment. Asbestos workers with malignant pleural mesothelioma have an average survival time of 11.4 months from symptom onset to death, and most patients die within 1 year. The next step is to integrate scientific treatments more scientifically and develop new technologies to find more effective drugs and diagnostic methods that can be treated early.
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