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Asbestos users and Mesothelioma patients?

Is it inevitable that all people who worked with asbestos will get Mesothelioma? What are the symptoms?

Mesothelial cells normally line the body cavities, including the pleura, peritoneum, pericardium, and testis. Malignancies involving mesothelial cells in these body cavities are known as malignant mesothelioma, which may be localized or diffuse. Diagnosis is difficult because the results from fluid analysis of the effusion from the tumor are not usually diagnostic. Most, but not all, pleural malignant mesothelioma is associated with asbestos exposure. Of patients with pleural malignant mesothelioma, 77% have been exposed to asbestos in the past.

* Median survival for patients with malignant mesothelioma is 11 months. It is almost always fatal. Median survival based on histologic type is 9.4 months for sarcomatous, 12.5 months for epithelial, and 11 months for mixed. Approximately 15% of patients have an indolent course.

* Asbestos exposure is linked to at least 50% of patients developing malignant mesothelioma. Approximately 8 million people in the United States have been exposed to asbestos in the workplace. Family members are also exposed to asbestos embedded in the worker’s clothing. The combination of tobacco and asbestos exposure greatly increases the risk of developing pleural mesotheliom

History:

* Dyspnea and nonpleuritic chest wall pains are the most common presenting symptom.

* Chest radiographs show obliteration of the diaphragm, nodular thickening of the pleura, decreased size of the involved chest, and/or radiolucent sheetlike encasement of the pleura.

* A loculated effusion is present in more than 50% of patients, and a major portion of the pleura is opacified by the effusion.

* Chest discomfort, pleuritic pain, easy fatigability, fever, sweats, and weight loss are the other common accompanying symptoms. Patients may also be asymptomatic, with evidence of a pleural effusion noted incidentally on physical examination or by chest radiograph. Metastatic disease is uncommon at presentation and contralateral pleural abnormalities are usually secondary to asbestos-related pleural disease rather than metastatic disease.

* Approximately 60-90% of patients may have symptoms of chest pain or dyspnea.

Physical:

* Physical findings of pleural effusion are usually noted upon percussion and auscultation.

* In rare cases, malignant mesothelioma manifests as cord compression, brachial plexopathy, Horner syndrome, or superior vena cava syndrome. Death is usually due to infection or respiratory failure from the progression of mesothelioma.

* Primary sites include the pleura (87%), the peritoneum (5.1%), the pericardium (0.4%), and the right side of the thorax (more so than the left side, by a ratio of 1.6:1)

Causes:

* A substantial proportion of patients were exposed to asbestos in asbestos mills, shipping yards, mines, or their homes.

* The crocidolite in asbestos is associated with mesothelioma in miners, manufacturers (using asbestos), and heating and construction workers. The rod-shaped amphiboles are more carcinogenic than the chrysotile.

* Malignant mesothelioma has also been linked to therapeutic radiation using thorium dioxide and zeolite, a silicate in the soil.

* An etiological role for simian virus 40 in malignant mesothelioma has also been suggested. Asbestos exposure alone was associated with malignant mesothelioma, but SV 40 alone was not. Thus giving some epidemiological evidence that SV 40 is a possible cocarcinogen. Its direct role at this point is still controversial.

* Interleukin 8 has direct growth-potentiating activity in mesothelial cell lines.

Medical Care: Treatment options for the management of malignant mesothelioma include surgery, chemotherapy, radiation, and multimodality treatment.

* Chemotherapy

o Currently, cisplatin as a single drug had been used as the standard drug for phase III clinical trials. None of the standard treatment options has improved survival. The most active agents are anthracycline, platinum, and alkylating agents; each produces a response rate of 10-20%.

o Vogelzang et al presented the results of a phase III study of pemetrexed in combination with cisplatin versus cisplatin alone. Pemetrexed (500 mg/m2/d) and cisplatin (75 mg/m2/d) or cisplatin (75 mg/m2/d) was given on day 1. Both arms were given every 21 days. The median time to survival in the cisplatin/pemetrexed arm was 12.1 months versus 9.3 months for cisplatin alone. The response rate was 41.3% for the cisplatin/pemetrexed arm and 16.7% for the cisplatin arm. Folic acid and vitamin B-12 were given routinely to prevent the adverse effects of pemetrexed. This trial established the regimen as the standard choice for this disease.

o A 1999 phase II study by Byrne et al using cisplatin (100 mg/m2) on day 1 and gemcitabine (1000 mg/m2) administered intravenously on days 1, 8, and 15 of a 28-day cycle for 6 cycles showed response rates of 47.6% (complete and partial response), 42.8% (stable disease), and 9.5% (progressive disease). The median response duration was 25 weeks, progression-free survival was 25 weeks, and the overall survival was 41 weeks. Toxicity was mainly gastroenterologic and hematologic in nature.

o Several other combinations have been found to be active, including cisplatin/doxorubicin (Adriamycin)/mitomycin C, bleomycin/intrapleural hyaluronidase, cisplatin/doxorubicin (Adriamycin), carboplatin/gemcitabine, and cisplatin/vinblastine/mitomycin C. The cisplatin/gemcitabine combination has yielded the best results.

o With the isolation of mesothelial cell lines, several chemotherapeutic agents are being tested actively to assess their efficacy. One explanation for the poor response to chemotherapy is the low apoptotic rate, as evidenced by low BCL2 and BAX expression. These data suggest that apoptosis is not a key phenomenon in mesothelioma development and histologic differentiation.

o Numerous trials of chemotherapeutic agents have been performed; however, until recently, the studies were small, the staging systems used were different, and the measurements of disease were inaccurate.

* Radiation

o Results with radiation therapy are also disappointing.

o Radiation has no effect on survival, but it has caused significant palliation in 50% of patients treated for chest pain and chest wall metastasis.

* Trimodality therapy

o This involves a combination of all 3 standard strategies (ie, surgery, chemotherapy, radiation).

o One trimodality approach involved extrapleural pneumonectomy followed by combination chemotherapy and radiotherapy. Overall survival rates were 45% at 2 years and 22% at 5 years.

o Lymph node involvement was a significant negative prognostic factor. The epithelial type had a better survival rate compared with the sarcomatous or mixed type (65% vs 20% at 2 y and 27% vs 0% at 5 y).

o Survival based on the Brigham staging system was 22 months for stage I, 17 months for stage II, and 11 months for stage III.

o Overall median survival was 17 months, yielding a 2-year survival rate of 36% and a 5-year survival rate of 14%. Epithelial cell type survival was better, with a 2-year survival rate of 68% and 5-year survival rate of 46%.

o Different chemotherapeutic regimens found to be useful in the trimodality treatment include cyclophosphamide/doxorubicin (Adriamycin)/cisplatin, carboplatin/paclitaxel, and cisplatin/methotrexate/vinblastine. External beam radiotherapy is delivered in a standard fractionation over 5.5-6 weeks.

Surgical Care: Surgical resection has been relied upon because radiation and chemotherapy have been ineffective primary treatments. The 2 surgical procedures used are pleurectomy with decortication and extrapleural pneumonectomy.

* Pleurectomy with decortication is a more limited procedure and requires less cardiorespiratory reserve. It involves dissection of the parietal pleura, incision of the parietal pleura, and decortication of the visceral pleura followed by reconstruction. It has a morbidity rate of 25% and a mortality rate of 2%. It is a difficult procedure because the tumor encases the whole pleura; the local recurrence rate is high.

* Extrapleural pneumonectomy is a more extensive procedure and has a higher mortality rate. Recently, the mortality rate has been lowered to 3.8%. It involves dissection of the parietal pleura; division of the pulmonary vessels; and en bloc resection of the lung, pleura, pericardium, and diaphragm followed by reconstruction. It provides the best local control because it removes the entire pleural sac along with the lung parenchyma.

* With surgery alone, the recurrence rate is very high and most patients die after a few months. At least half the patients who have local control with surgery have distant metastasis upon autopsy.

Consultations:

* If an infection is suggested initially, consultation with a pulmonary specialist is essential if the infection does not resolve within 2 weeks with adequate antibiotic treatment.

* Chest radiographs are mandatory for follow-up if the infection has resolved. If the patient has diffuse calcification of the pleura and a history of weight loss with chronic cough, a full evaluation by a pulmonary specialist and oncologist is necessary.

* A referral for thoracoscopy is warranted if the diagnosis is considered and the initial workup is not diagnostic.

* Occupational history is important, and family members with exposure to asbestos should also be evaluated.

Diet:

* Patients are usually cachetic after surgery, chemotherapy, and radiation. Good supportive care and a regular nutritional status assessment are warranted. Patients should be referred to a nutritionist.

Activity:

* Beginning physical activity as soon as possible is important to prevent postoperative complications.

* Pulmonary physiotherapy is very helpful because of the extensive lung resection in such patients.

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This entry was posted on Tuesday, November 17th, 2009 at 8:10 pm and is filed under Mesothelioma Cancer Lawyer. You can follow any responses to this entry through the RSS 2.0 feed. You can leave a response, or trackback from your own site.