For the incidence of pleural mesothelioma has continued to rise around the world. Most of pleural mesothelioma is a curable tumor, it occurs more concerned with long-term exposure to asbestos. In 2001, documents that have a genetic predisposition of pleural mesothelioma, but some scholars do not agree with.
According to WHO on the lung and pleural tumors in the latest classification, pleural mesothelioma can be divided into epithelial, sarcoma, and fibroma-like mix of cells in pleural mesothelioma, epithelial mesothelioma in which the prognosis is better than other types. Malignant pleural mesothelioma and other cancers, especially adenocarcinoma of the usually very difficult to identify, immunohistochemical examination to become an important method of diagnosis of mesothelioma (see Table 8.1). Camera with chest CT is to assess the extent of the lesion of the key steps. Radiological imaging used for pleural effusion and pleural thickening. Pleural effusion by thoracic puncture more than confirmed, but cytology-positive rate is very low. Existence of pleural effusion, pleural biopsy without imaging guidance in general can be carried out. However, in some patients, in order to determine the nature of pleural lesions, in need of thoracoscopic biopsy.
Adams and other reported 18 cases of the image-guided percutaneous needle aspiration of pleural biopsy, the histological diagnosis of up to 86% sensitivity and specificity of up to 100%. Only one cases of chest wall complications of bleeding and 1 case of mild hemoptysis. Puncture using 14-18G needle biopsy, 6 patients with ultrasound-guided, 15 patients with CT guidance. Some tumor markers, such as CYFRA21-1 and CEA testing can be used as complementary diagnostic cytology. Experiment detected 106 cases of patients (34 cases of benign lesions, primary tumor and metastasis of bronchial carcinoma 40 cases, 32 cases of pleural mesothelioma) and pleural effusion and serum CEA and CYFRA21-1 levels. Malignant pleural effusion CYFRA21-1 and CEA were 78% sensitivity and 30.6%, while specificity were 80% and 91%. CYFRA21-1 and CEA in pleural mesothelioma, a sensitivity of 87.5% and 3.1% respectively. 19 patients with negative or suspicious cytology in 17 cases of mesothelioma CYFRA21-1-positive. 32 cases of mesothelioma in 30 patients with markers and cytology diagnosis. Therefore, CYFRA21-1 increased the CEA level is not high, suggesting that for mesothelioma, but simply elevated CEA levels and both of which may be prompted to malignant pleural effusion, mesothelioma can be ruled out.
After analysis of microvessel density, the European Organization of Research and Treatment of Cancer (EORTC) that the vascular growth factor is an independent prognostic factor. But the Cancer and Leukemia Group (CALGB) with anti-CD34 antibodies on 104 cases of mesothelioma are organized chemical analysis of surgical specimens, that the factor is not independent prognostic factors. And other adverse independent prognostic factor for non-epithelial cell type (p = 0.002) and physical status score greater than 0 (p = 0.003).
Another experiment detected by immunohistochemistry in 32 cases of mesothelioma tumor tissue, high expression of catalase in the proportion of 75%, while the normal control group, compared with 0. High expression of catalase indicated a good prognosis. Another author reported 30 cases of mesothelioma in 22 cases of tumor tissue fatty acid content was significantly higher than in normal tissues (including the mesothelial organizations), suggesting that fatty acids may be an effective target for drug therapy.
Table 8.1 pleural lesions by immunohistochemistry (WHO / IASLC)
Diagnosis Keratins (LMW / HMW) CEA B72.3 Leu-M BER-EP4 EMA HMFG-2 Vimentin Actin
Mesothelial hyperplasia + ~ + + - - - - - / + - / + --
Epithelial mesothelioma + ~ + + - / + - / + - / + - / + + + - / +
Metastatic carcinoma (adenocarcinoma) + ~ + + + + + + + - / + --
Fibrous pleurisy + - - - - - / + + +
Sarcomatoid mesothelioma + - - - - - / + + + / --
Primary / metastatic sarcoma + / - - - - - - + ※
Note: -: Negative ;-/+: mostly negative ;+/-: dual positive; +: mostly positive; + +: strong positive; ※: based on a different type of
Treatment
The treatment of malignant pleural mesothelioma, regardless of what conventional treatment effects are disappointing. Radical surgery such as extrapleural pneumonectomy, only apply to very few cases of limited disease. Surgeon but also try to palliative cytoreductive surgery. In a prospective study, 51 patients had implemented in order to control the symptoms for the purpose of palliative debulking surgery. Pleural effusion, if discharged after a successful lung reexpansion, viable subtotal pneumonectomy. In case of lung collapse, then the possible dirty, parietal pleura endarterectomy. Surgery, there may be difficulty in breathing, pain, a small number of patients with empyema and pneumothorax may occur. The symptoms improved significantly after up to 3 months, but the operative mortality rate can increase. Epithelial cell type and post-operative body weight without reducing the survival of patients indicates that longer-term and good symptom control.
In recent years, resistance of malignant mesothelioma related to the literature. Soini and other comparative study of 36 cases of malignant pleural mesothelioma and normal mesothelial tissue P-gp and multidrug resistance protein (MRP1, MRP2) expression. Malignant mesothelioma tissue P-gp, MRP1, and MRP2-positive rates were 61%, 58% and 33%, while the normal mesothelial tissue is not multi-drug resistance protein expression. P-gp and MRP2 expression was significantly related to both. The expression has nothing to do with the patient's survival, indicating that the resistance mechanism of mesothelioma is not just determined by P-gp or MRP expression and function.
Table 8.2 lists a number of drugs (such as liposome daunorubicin, gemcitabine, ranpirnase, IL-2) single-agent efficacy of the treatment of mesothelioma. In all four Phase Ⅱ clinical trials, efficacy is not satisfactory, the former three drugs are effective for the 0,0 and 3%, gemcitabine and ranpirnase the median survival time was 4.7 months and 6 months. Efficacy of IL-2 chest perfusion was relatively good. Pleural perfusion the toxicity of IL-2 is mainly fever, incidence of about 19%. Clinical evaluation based on WHO criteria, an objective assessment by CT scan, and 1 CR, 6 Li PR, and another 10 cases of stability and progress in 14 cases. The median survival time was 15 months (range 5-39 months).
Table 8.2 single-agent treatment of malignant mesothelioma: Phase II clinical results
Dose usage of a number of cases in an efficient and effective number of cases (%) b Evaluation
CR PR Total
Daunorubicin liposomes 120mg/m2 iv. Every 3 weeks 1 140,000 (0-23) --
Gemcitabine 1500mg/m2 iv. Every 3 weeks 1 180,000 (0-18), the median survival time was 4.7 months, one year survival rate was 24%
Ranpirnase 480ug/m2 iv. Week 1 810,444 (1-12), the median survival: intent-line treatment group for 6 months, targeting the treatment group 8.3 months
IL-2 9106IU, thoracic perfusion, 2 times per week for 4 weeks 31,172,222 (9-41), the median survival time was 15 months (range 3-39 months)
Note: a CR: complete remission; PR: partial remission
b in parentheses 95% confidence limits
Table 8.3 for the combination chemotherapy information. Overall, the efficacy of combination chemotherapy is higher than single-agent chemotherapy, and roughly 1.6% ~ 38%. The median survival time is also very similar, namely, 9.3,9.6,10.5, 17.5 months. Two experiments with traditional cytotoxic drugs made up of two drugs and three drug programs, the Italian author and British authors, respectively, in the joint program was added IFN-α2b and SRL172. Which combined with chemotherapy combined SRL172 intratumoral injection or thoracic perfusion, 33% achieved an objective and efficient. The experimental combination of chemotherapy and immunotherapy prompted preparations, although cytotoxic drugs can produce mild immune suppression, but it can promote the release of tumor antigens and presenting, in the immune modulators (eg, SRL172) co-stimulated tumor-specific immunity under reaction.
Table 8.3 Combined chemotherapy of pleural mesothelioma
The number of cases of effective treatment programs effective number of cases (%) a rating
CR PR Total
Gemcitabine + Cisplatin 2,504,416 (1-31), the median survival time was 9.6 months
Mitoxantrone-Kun + methotrexate + mitomycin 2216732 (12-51), the median survival time was 13.5 months
Cisplatin + doxorubicin + IFN-α2b 35 0 0 10 29 (15-47) The median survival time 9.3 months, 1 year, 2-year survival rates were 45% and 34%
Mitomycin + cisplatin + vincristine + (SRL172) 15 0 0 6 37.5 (16-67) the median survival time 10.5 months
Ifosfamide + carboplatin + etoposide + hyperthermia b 15 0 5 5 33 (11-62) --
Note: a: in brackets 95% confidence limits
b: 41.8 (60 min) total body irradiation heating
New therapy:
Alimta (pemetrexed for injection, pemetrexed disodium); the treatment of malignant pleural mesothelioma, a good efficiency,
[Mechanism]: thymidylate synthase (thymidylate synthase) / double dihydrofolate reductase inhibitors, anti-metabolic anti-cancer drugs.
【Usage and Dosage】
Alimta can only be intravenous infusion, and cisplatin in conjunction with the recommended dose of 500 mg/m2, day 1, infusion of more than 10 minutes, 21 days cycle. The recommended dose of cisplatin 75 mg/m2, in the Alimta infusion beginning 30 minutes after the infusion, more than 2 hours.
Creatinine clearance> 45 ml / min in patients without dose adjustment, the rate of creatinine clearance <45 ml / min is not recommended in patients with the use of Alimta.
Patients receiving Alimta should also use folic acid and vitamin B12, can reduce treatment-related hematologic toxicity and gastrointestinal toxicity.
Traditional Chinese medicine: Chinese Cancer Information Library cooperation in a number of cancer patient application of domestic asparagus capsule, Kangai injection, Qingfei Sanjie pills, golden mouth rehabilitation fluid, sen toad films, Haiwei mixture of swelling of the liver combined with external paste ferulic plaster and other drugs symptomatic treatment of pleural mesothelioma to achieve some effects.
Friday, November 27, 2009
Subscribe to:
Comments (Atom)