The Journal of Thoracic and Cardiovascular Surgery

The Journal of Thoracic and Cardiovascular Surgery, January 1999 by Dr. David J. Sugarbaker

RESECTION MARGINS, EXTRAPLEURAL NODAL STATUS, AND CELL TYPE DETERMINE
POSTOPERATIVE LONG-TERM SURVIVAL IN TRIMODALITY THERAPY OF MALIGNANT PLEURAL
MESOTHELIOMA: RESULTS IN 183 PATIENTS

Objectives: Our aim was to identify prognostic variables for long-term
postoperative survival in trimodality management of malignant pleural
mesothelioma. Methods: From 1980 to 1997, 183 patients underwent
extrapleural pneumonectomy followed by adjuvant chemotherapy and
radiotherapy. Results: Forty-three women and 140 men (age range 31-76
years) had a median follow-up of 13 months. The perioperative mortality
rate was 3.8% (7 deaths) and the morbidity, 50%. Survival in the 176
remaining patients was 38% at 2 years and 15% at 5 years (median 19
months). Univariate analysis identified 3 prognostic variables associated
with improved survival: epithelial cell type (52% 2-year survival, 21%
5-year survival, 26-month median survival; P = .0001), negative resection
margins (44% at 2 years, 25% at 5 years, median 23 months; P =
.02), and extrapleural nodes without metastases (42% at 2 years, 17% at
5 years, median 21 months; P = .004). Using the Cox proportional hazards,
the relative risk of death was calculated for nonepithelial cell type
(OR 3.0, CI 2.0-4.5; P < .0001), positive resection margins (OR 1.7, CI
1.2-2.6; P = .0082), and metastatic extrapleural nodes (OR 2.0, CI 1.3-
3.2;P = .0026). Thirty-one patients with 3 positive variables had the best
survival (68% 2-year survival, 46% 5-year survival, median 51 months;
P = .013). A previously published staging system using these variables
stratified survival (P < .05). Conclusions: (1) Multimodality therapy
including extrapleural pneumonectomy is feasible in selected patients
with malignant pleural mesotheliomas, (2) pre-resectional evaluation of
extrapleural nodes may select patients for radical therapy, (3) microscopic
resection margins affect long-term survival, highlighting the need
for further investigation of locoregional control, and (4) patients with
epithelial, margin-negative, extrapleural node–negative resection had
extended survival. (J Thorac Cardiovasc Surg 1999;117:54-65)

It was estimated that 2200 to 3000 new cases of mesothelioma would be diagnosed in the United States in 1998.1-3 The natural history of malignant pleural mesothelioma includes a median survival of 4 to 12 months without intervention,4-6 and there is no accepted standard therapy. The biologic behavior of malignant pleural mesothelioma is unique among thoracic malignant disease. It has shown a natural history of relentless
local progression with rare hematogenous spread even in the late stages of untreated disease.7 Even after aggressive local control measures, locoregional recurrence is the fate of a majority of patients.8Extended survival has been reported in patients undergoing multimodality therapy of radical extrapleural pneumonectomy followed by chemotherapy and radiation.9-13 The difficulty in this management of the disease has been to differentiate patients most likely to benefit from this aggressive approach from those patients destined to die early of the disease.Since 1980, The Brigham and Women’s Hospital applied extrapleural pneumonectomy for malignant pleural mesothelioma in the context of trimodality therapy.Two earlier reports of this series have reviewed the results of 52 and 120 patients.13,14 We now review our
results with 183 consecutive patients and analyze prognostic variables among the 176 long-term survivors.These variables form the basis of a revision of our published14
staging system. We also wish to assess the feasibility of this approach in the light of this larger patient cohort in preparation for future clinical trials and lternative treatment strategies.Patients and methods We reviewed 183 consecutive patients with diffuse malignant pleural mesothelioma treated with extrapleural pneumonectomy followed by adjuvant chemotherapy and radiotherapyfrom 1980 to 1997 at The Brigham and Women’s Hospital,the Dana-Farber Cancer Institute, and the Joint Center for Radiation Therapy (Boston, Mass). Survival data were obtained by reviewing hospital and office records and by contacting patients or their primary care physicians. All surviving patients were cross-sectionally contacted in September 1997.All pathologic material establishing the diagnosis of malignant pleural mesothelioma was reviewed by The Brigham and Women’s Hospital Pathology Department for confirmation. If a definitive diagnosis could not be made on tissue available,
a pleuroscopy and biopsy under direct vision was performed.A multimodality team comprising a medical oncologist, a surgeon, and a radiation oncologist evaluated all patients with histologically proven malignant pleural mesothelioma.Patients were considered surgical candidates if they had a Karnofsky performance status of greater than 70%, a creatinine level within normal limits, liver function test results
within the normal range, and tumor judged to be completely resectable on the basis of computed tomographic scan, magnetic resonance imaging (MRI), and echocardiography.
Physiologic exclusion criteria included room air arterial PCO2 greater than 45 mm Hg, room air arterial PO2 less than 65 mm Hg, echocardiography demonstrating an ejection fraction of less than 45%, and a predicted postoperative forced expiratory volume in 1 second (FEV1) of less than 1 L. Patients with a preoperative FEV1 of less than 2 L underwent quantitative radionuclide ventilation-perfusion scanning to predict ostoperative pulmonary function more accurately.Trimodality treatment consisted of extrapleural pneumonectomy followed by postoperative intravenous chemotherapy
and radiotherapy. Extrapleural pneumonectomy entailed resection of the pleura, lung, diaphragm, and pericardium en bloc.15 Separate resection of prior open biopsy
sites, thoracoscopy incisions, and chest tube tracks included a 1-cm margin of normal tissue.
A standardized pathologic analysis was routinely undertaken for each specimen. First, a gross examination of the specimen was performed by the pathologist to determine any obvious areas of tumor remaining at the resection margins.Then, approximately 20 sections were taken through each specimen to ascertain whether ositive microscopic marginsremained along the chest wall. The bronchus, pericardium,
and diaphragm were carefully examined for microscopic margins. A positive margin identified on the specimen was then used to direct postoperative thoracic radiation treatment.Extrapleural pneumonectomy at our institution has always included nodal sampling of hilar, paraesophageal, inferior pulmonary ligament, peridiaphragmatic, and subcarinal nodal stations. Additionally, right extrapleural pneumonectomies
had sampling of paratracheal nodes, and left extrapleural pneumonectomies included sampling of aortopulmonary window nodes. Involvement of these nodes has been etermined in a standardized fashion by the same senior pathologist(J. M. Corson) throughout this series of patients.Extrapleural nodes are defined as mediastinal lymph nodes and peridiaphragmatic lymph nodes not located within the pleural reflection. Intrapleural nodes are defined as any lymph node located within the pleural envelope. Each patient’s status was staged by Butchart criteria,9 the new
international TNM mesothelioma staging system,16 and the system previously published by this group.14 Chemotherapy was initiated 4 to 6 weeks after convalescence
from extrapleural pneumonectomy. Nine patients treated before 1985 received doxorubicin 50 to 60 mg/m2 and cyclophosphamide 600 mg/m2 for 4 to 6 cycles. Eighty
patients treated from 1985 to 1994 also received cisplatin 70 mg/m2 added to the previous regimen (CAP). Ninety-four patients undergoing treatment from 1995 to 1997 received carboplatin (Paraplatin; Bristol Myers Squibb, Princeton, NJ)and paclitaxel (Taxol; Bristol Myers Squibb) at dosages of an area under the curve (AUC) of 6 and 200 mg/m2, respectively.Although chemotherapy was started between 4 and 6 weeks
after extrapleural pneumonectomy, it was started up to 12 weeks after the operation if a patient had major postoperative morbidity. Patients received 2 cycles of carboplatin/ paclitaxel chemotherapy 3 weeks apart, followed by the prescribed
course of radiation therapy with concurrent weekly paclitaxel.Beginning 3 to 4 weeks after completion of radiation therapy,patients received 2 additional cycles of carboplatin and paclitaxel 3 weeks apart.External beam radiotherapy was delivered with the use of linear accelerators ranging in energy from 4 to 15 MV. The total radiation dose to the hemithorax was typically 30 Gy delivered in 1.5-Gy fractions, and the mediastinum received 40 Gy. A boost dose was given to areas of gross residual disease,localized positive resection margins, and/or localized lymph nodes. The boost dose, if given, was typically 14 Gy in 2-Gyfractions for a total cumulative dose to the boost region of 54 Gy.Because clinical symptoms and radiographic studies are not
sensitive enough to accurately diagnose early recurrence, the disease-free interval is difficult to measure. Therefore survival is the major end point of this study. The survival duration was measured from the date of extrapleural pneumonectomy until
the date of the patient’s last follow-up contact or death.Perioperative mortality is defined as death occurring within 30 days of the operation. Morbidity is defined as an untoward event directly resulting in prolonged hospitalization.Statistical analysis of survival was undertaken by use of a landmark of 30 days after surgical resection. Univariate analysis was performed by means of the Kaplan-Meier lifetable
method to determine the effects of demographic and pathologic variables. The log rank test was used to determine statistical significance of comparisons among survival
curves. Dichotomous variables included smoking history,asbestos exposure, chest pain, dyspnea, cough, age greater or less than 65 years, side of tumor, sex, cell type (epithelial versus mixed and sarcomatous), tumor at surgical margins, and
metastases to extrapleural nodes. Results with a P value of less than .05 were considered significant and were included in a multivariate proportional hazards regression model. This generated an odds ratio of death for each variable associated
with shortened survival.Variables found to be significant on multivariate analysis
were used to modify our previously published surgical staging system. Log rank tests were used to determine the statistical significance of survival comparisons between stage groupings.Results Demographics. The overall analysis included 183 patients who initiated therapy by undergoing extrapleural pneumonectomy at The Brigham and Women’s
Hospital from 1980 to 1997. The cohort included 43 women and 140 men with a mean age of 57 years (range 31-76 years). Forty-nine (27%) patients were aged 65 years or older. Median follow-up interval was 13 months (range 0.2-100 months) and follow-up is complete through September 1997. Of the 183 patients,117 (65%) reported a smoking history and 132 (75%)had known asbestos exposure. One hundred two (56%)reported a history of chest pain, 133 (73%) reported a history of dyspnea, and 65 (36%) reported a history of cough. Eighty-two patients (45%) had pleural mesothelioma of the left side of the chest, and 101 had rightsided tumors.Morbidity and mortality. Morbidity was divided into major and minor subtypes. Major morbidity was defined as an untoward event leading to longer hospital stay and occurred in 45 of the 183 patients (24.5%).
Major cardiovascular morbidity occurred in 7 patients:cardiac arrest (n = 5), right ventricular failure (n = 1),and left ventricular failure (n = 1). Pulmonary morbidity
(n = 15) included patients with aspiration (n = 5),pulmonary failure (n = 5), pulmonary embolus (n = 3),and contralateral pneumothorax (n = 2). Infectious
morbidity (n = 9) causes included sepsis (n = 4), wound infection (n = 3), empyema (n = 1), and bacteremia (n= 1). Gastrointestinal morbidity (n = 7) included bleeding in the upper gastrointestinal tract (n = 2), perforated duodenal ulcer (n = 2), colectomy for Clostridium difficile colitis (n = 1), Ogilvie’s syndrome (n = 1), and
pancreatitis (n = 1). Technical morbidity (n = 12) included patients who underwent re-exploration for bleeding or suspected cardiac tamponade (n = 9),diaphragmatic patch rupture (n = 2), and cardiac herniation (n = 1). Other miscellaneous morbidity (n = 18)included patients with vocal cord paralysis (n = 10),deep venous thrombosis (n = 4), seizure (n = 2), and acute renal failure (n = 2).Minor morbidity included atrial and ventricular arrhythmias, which occurred in 75 patients (41%).These arrhythmias were treated with cardioversion or pharmacologic therapy without lengthening hospital stay. Specifically, atrial fibrillation occurred in 68
patients (37%) and ventricular arrhythmias occurred in 7 patients (3.8%). Overall, some morbidity occurred in 92 patients (50%).There were 7 perioperative (30-day) deaths (3.8%).Three patients died of pulmonary embolus, 2 died of myocardial infarction, 1 of cardiac herniation through a pericardial defect, and 1 of respiratory failure. The median postoperative length of stay was 9 days (range 5-101 days).Long-term survival. The 30-day survival landmark was reached by 176 patients. The median survival for these patients was 19 months; 2- and 5-year survivals were 38% and 15%, respectively (Fig 1).Demographic variables not significantly associated
with duration of survival within this group of 176 longterm survivors included age greater than or equal to 65 years (P = .10 ), cigarette use (P = .33), asbestos xposure (P = .38), chest pain (P = .15), dyspnea (P = .19),cough (P = .92), and side of tumor (55% right; P = .70).Female sex was associated with improved survival on
univariate analysis (P = .03) but was not significant in the multivariate model (P = .16).Epithelial cell type (Fig 2), negative resection margins (Fig 3), and lack of extrapleural lymph nodal involvement (Fig 4) were significant prognostic factors
associated with prolonged survival in univariate analysis.The 103 (59%) patients with epithelial cell type tumors had 2- and 5-year survivals of 52% and 21%,respectively (Fig 2). By contrast, the survival for the 73 patients with sarcomatous or mixed cell type was 16% at 2 years, and no patient survived 5 years (P = .0001;Fig 2). The 66 patients with negative resection margins had a 2-year survival of 44% and a 5-year survival of 25% compared with the 110 patients with positive resection margins, who had a 2-year survival of 33% and a 5-year survival of 9% (P = .02; Fig 3). The 136
patients with negative extrapleural nodal status had a 2-year survival of 42% and a 5-year survival of 17%; the 40 patients with positive extrapleural nodal status had a
2-year survival of 23%, and none survived 5 years (P =.004; Fig 4). Eleven patients had metastases to the extrapleural peridiaphragmatic nodes but not to the
mediastinal nodes. We considered metastases to extrapleural peridiaphragmatic nodes to act like metastases to mediastinal nodes because they lay within the same nodal drainage bed as the station 8 (periesophageal)and station 9 (inferior pulmonary ligament)nodes in the American Thoracic Society lymph node map for lung cancer.
The 4 significant variables identified by the log rank test were entered in a Cox proportional hazards model.Gender was no longer a significant predictor of long-term survival (P = .03). Odds ratios of death and confidence intervals for the remaining 3 prognostic variables are listed in Table I.Our previously published staging system14 was also used to stage this cohort of patients. By this method,survival was significantly stratified by stage (P = .048).Median survival intervals for patients with stage I (n =66), II (n = 41), and III (n = 69) disease were 25, 20,and 16 months, respectively. The identification of these predictive variables by the Cox proportional hazards model led us to revise our previous staging system to account for positive margins and extrapleural nodes(Table II). When the criterion of extrapleural nodal involvement was reassigned from stage II to stage III,survival stratification was improved (Fig 5). This revised staging system significantly stratified long-term survival (P = .0011). This same cohort was not stratified by the new international TNM system for mesothelioma16(P = .31) or by the Butchart staging system9 (P= .09).A subset of 31 patients with epithelial cell type, negative
resection margins, and negative extrapleural nodal status had a 51-month median survival with a 2-year survival of 68% and a 5-year survival of 46% (Fig 6).This most favorable group with stage I disease and epithelial cell type had significantly better long-term survival than did patients with stage II and stage III epithelial disease (P = .0044).Discussion This study suggests (1) multimodality therapy of
malignant pleural mesothelioma combining extrapleural pneumonectomy with adjuvant chemoradiotherapy is feasible with acceptable perioperative mortality (3.8%); (2) a subgroup of patients with epithelial cell type, negative extrapleural nodes, and complete resection margins have a long-term median survival approaching 5 years; (3) research efforts should be directed toward devising improved methods of obtaining
local control; (4) pre-resectional extrapleural node staging may play an important role in deciding treatment strategy; and (5) the staging system previously
published14 significantly stratified survival. Finally, we propose a revision to our previously published staging system.This study demonstrates in a large patient cohort that extrapleural pneumonectomy is a safe means of cytoreduction.In 1976, Butchart and associates9 reported their experience with extrapleural pneumonectomy but
demonstrated a prohibitively high perioperative mortality rate of 31%. The advent of improved surgical techniques,hemostasis, prosthetic reconstruction of the diaphragm and pericardium, advances in intraoperative and postoperative monitoring, and better critical care support have since improved postoperative outcome to our current rate of 7 deaths in 183 operations (3.8% mortality).The major operative morbidity in this cohort was 24.5%, but many of the complications do not present major setbacks when treated appropriately. Atrial fibrillation occurred in 37% but was well controlled with calcium channel blockers, digoxin, procainamide, or a combination of these gents. No patient had severe consequences as a result of this complication. It is possible that rapid filling within the denuded hemithorax results in respiratory distress because the dense fluid shifts the mediastinum toward the remaining lung and
compresses it. Aspiration of the fluid-filled hemithorax,as demonstrated in 6 of our patients, leads to repositioning of the mediastinum, decrease in intra-abdominal pressure, and subsequent lung re-expansion followed by resolution of hypoxia. The attendant morbidity and potential mortality from extrapleural pneumonectomy stresses the importance of performing the procedure at specialized institutions.The current regimen of combined carboplatin-paclitaxel adjuvant chemotherapy was designed in 1995.Platinum-based chemotherapy yielded a response in 7 of 15 (47%) patients with peritoneal mesothelioma17 and in 18% with pleural mesothelioma.18 Paclitaxel as
a single agent in advanced pleural mesothelioma produced regression in 2 of 15 (13%) and stable disease in 5 of 15 (33%) patients treated by the Cancer and Leukemia Group B (CALGB) in 1993.19 In 1995 Herscher and colleagues20 reported local control of advanced pleural mesothelioma with single-agent paclitaxel in 7 of 8 (88%) patients. Although there were no combination data of carboplatin-paclitaxel in malignant pleural mesothelioma, these 2 agents had recognized single-agent activity against this chemotherapyresistant disease. Furthermore, there were published data on the use of carboplatin-paclitaxel combinations in the treatment of advanced breast, ovarian, and lung cancers with high response rates: 78% to 94% in breast cancer,21,22 57% to 81% in ovarian cancer,23,24 and 38% to 86% in lung cancer.25-31 The rationale for this approach has been steadily evolving in the literature.Cisplatin and paclitaxel as single agents were each effective against some in vivo mesothelioma cell lines
in athymic nude mice, but they were more effective in all cell lines when given in combination.32 Carboplatin-paclitaxel was recognized as a better tolerated chemotherapy regimen than the CAP (cyclophosphamide-doxorubicin-platinum) regimen it replaced.Less toxicity for patients after pneumonectomy would suggest more patients will receive adjuvant therapy.In other types of malignant disease, chemotherapy is
more effective in the setting of minimal residual tumor burden,33 although this remains unproven in pleural mesothelioma.Extrapleural pneumonectomy combined with adjuvant chemoradiation therapy by this protocol offers improved survival for certain subgroups of patients.Specifically, patients with epithelial cell type, lack of
extrapleural nodal involvement, and negative surgical margins have a median survival approaching 5 years.The patients with non-epithelial cell type (sarcomatoid and mixed cell type) have a significantly worse survival,with only 16% living for 2 years after the operation.This suggests that our current trimodality treatment plan is having a small impact within this group with unfavorable histologic features, and new trategies for local control are needed. One possibility would be to apply chemotherapy combinations currently administered in the treatment of sarcomas such as MAID(methotrexate, Adriamycin [Pharmacia & Upjohn,Kalamazoo, Mich], ifosfamide, and prednisone) instead of carboplatin-paclitaxel combinations that have demonstrated responses against epithelial tumors.Mesothelioma, unlike lung cancer, tends to progresslocally rather than systemically. Of the 54% of patients with recurrences reported by Baldini and colleagues,867% had recurrences within the ipsilateral emithorax finding,13 which we attribute to the larger number of patients in the current study cohort. Taken together,these observations suggest that future nvestigative efforts should be directed toward more effective methods of locoregional control.Pass and colleagues35 have studied the role of intraoperative photodynamic therapy as a method of local control in the treatment of malignant pleural mesothelioma.They have performed a phase I trial to determine the maximally tolerated dose. However, they recently published the results of a phase III trial indicating that this treatment did not appear to prolong survival or improve local control when performed after surgical debulking.36Rusch and colleagues37,38 have extensively studied pleurectomy and postoperative intrapleural chemotherapy.Their results have shown only marginal improvement in outcome without significant toxicity. In
patients undergoing pleurectomy,gross residual tumor frequently remains within the hemithorax. Given the millimeter level of penetration of intracavitary chemotherapy,
the amount of cytoreduction with pleurectomy may be inadequate to allow the intracavitary chemotherapy to work optimally.39-42 In patients undergoing
extrapleural pneumonectomy, residual tumor within the hemithorax is most often microscopic, presenting a smaller tumor burden to be controlled with intracavitary
chemotherapy. Kodama and colleagues43 have used hyperthermic intrathoracic chemotherapy in patients undergoing resection for adenocarcinoma with evidence of improved local control. No data exist in patients with malignant pleural mesothelioma after surgical resection.The dismal survival of patients with extrapleural nodal involvement suggests a role for pre-resectional lymph node staging. Either ediastinoscopy or positron emission tomography (PET) scanning may play a useful role in patient selection. Although paraesophageal lymph nodes are inaccessible by ediastinoscopy,a positive finding of a diseased mediastinal node is useful nonetheless. Data on the detection of mediastinal nodes via mediastinoscopy and PET scanning are nonexistent in patients with mesothelioma. The pattern of mesothelioma tumor spread does not appear to follow an ordered lymphatic pattern like that seen in lung cancer, and studies establishing the sensitivity and specificity of ediastinoscopy in this particular disease are needed.We recommend that patients with a histologic diagnosis of sarcomatoid or biphasic mesothelioma and comorbid disease undergo mediastinoscopy because the combination of both sarcomatoid or mixed cell
and 50% had recurrences within abdominal regions; a majority of these recurrences appeared to result from direct extension from the ipsilateral hemithorax. Recurrences
are thought to result from trauma, spillage,and residual tumor at the resection margins that subsequently are entrapped in fibrin deposits and become exposed to postoperative growth factors.34 In this study,patients with positive resection margins had a median survival of 15 months (33% 2-year survival, 9% 5-year survival) and patients with negative resection marginshad a median survival of 23 months (44% 2-year survival,25% 5-year survival; P = .02). Our previous report on the first 120 patients did not demonstrate this finding,13 which we attribute to the larger number of patients in the current study cohort. Taken together,these observations suggest that future investigative efforts should be directed toward more effective methods
of locoregional control.Pass and colleagues35 have studied the role of intraoperative
photodynamic therapy as a method of local control in the treatment of malignant pleural mesothelioma.They have performed a phase I trial to determine the maximally tolerated dose. However, they recently published the results of a phase III trial indicating that this treatment did not appear to prolong survival or improve local control when performed after surgical debulking.36 Rusch and colleagues37,38 have extensively studied pleurectomy and postoperative intrapleural chemotherapy.Their results have shown only marginal improvement in outcome without significant toxicity. In patients undergoing pleurectomy, gross residual tumor frequently remains within the hemithorax. Given the millimeter level of penetration of intracavitary chemotherapy,the amount of cytoreduction with pleurectomy may be inadequate to allow the intracavitary chemotherapy to work optimally.39-42 In patients undergoing extrapleural pneumonectomy, residual tumor within the hemithorax is most often microscopic, presenting a smaller tumor burden to be controlled with intracavitary
chemotherapy. Kodama and colleagues43 have used hyperthermic intrathoracic chemotherapy in patients undergoing resection for adenocarcinoma with evidence
of improved local control. No data exist in patients with malignant pleural mesothelioma after surgical resection.The dismal survival of patients with extrapleural nodal involvement suggests a role for pre-resectional lymph node staging. Either mediastinoscopy or positron emission tomography (PET) scanning may play a useful role in patient selection. Although paraesophageal lymph nodes are inaccessible by mediastinoscopy,a positive finding of a diseased mediastinal node is useful nonetheless. Data on the detection of mediastinal nodes via mediastinoscopy and PET scanning are nonexistent in patients with mesothelioma. The pattern
of mesothelioma tumor spread does not appear to follow an ordered lymphatic pattern like that seen in lung cancer, and studies establishing the sensitivity and
specificity of mediastinoscopy in this particular disease are needed.We recommend that patients with a histologic diagnosis of sarcomatoid or biphasic mesothelioma and
comorbid disease undergo mediastinoscopy because the combination of both sarcomatoid or mixed cell types and positive extrapleural nodal status predicts a survival that mimics the natural history without surgical intervention. If pre-resectional nodal testing proves positive in high-risk patients with sarcomatoid or mixed tumors, we would not recommend proceeding with extended resection.The proposed International TNM Staging System16 and the Butchart staging system9 failed to stratify survival
when applied to our cohort of 176 patients. The TNM staging system placed 8% of our cohort into the stage I category, 11% into stage II, 78% into stage III,and 3% into stage IV. Since the majority of our cohort of 176 patients were categorized as stage III by TNM,it is difficult to separate patients with different tumor characteristics that are necessary to stratify survival in our patient cohort. In addition, the T descriptor alone was not a statistically significant predictor of survival,reflecting the inability of this system to describe the biologic behavior of this particular tumor.The system proposed by Butchart similarly did not significantly stratify survival. A small number of patients were categorized as having stage III disease (n
= 5, 3%). The distinction between extent of primary tumor involvement and ntrathoracic nodal involvement is not appropriately taken into account by this
staging system, as reflected by the majority of patients being placed in the stage II category.The staging system proposed previously by this group14 continued to stratify survival successfully. This is a surgical staging system based on the ability to completely remove all tumor within the pleural envelope and involved regional nodes. Observer bias may exist because this staging system originated at our institution
and was based on an earlier cohort. Validation by other institutions will be required to judge the utility of this clinical staging system.We considered peridiaphragmatic nodes to be extrapleural nodes in this analysis. Metastasis to peridiaphragmatic
nodes was associated with a similar median survival as metastasis to mediastinal nodes. However,if one considers only the 29 patients with metastases to the mediastinal nodes that could be reached by mediastinoscopy, there was a highly significant difference in long-term survival of these patients compared with patients with uninvolved mediastinal nodes (P = .0026).Because of the negative effect of extrapleural nodal disease on survival, we propose a revised staging system
to predict long-term survival (Table II). This staging system differs from our previous publication14 in that the presence of extrapleural node involvement has
now been included in stage III. This represents a distinction as to the location and extent of nodal involvement based on the poorer survival of patients in this
subgroup.A median survival of 51 months in the subgroup of patients with negative extrapleural lymph nodes is a ray of hope in the treatment of this dismal disease. We
believe it is no longer appropriate to offer only supportive care to all patients with mesothelioma because a subgroup of well-selected patients appears to benefit
from aggressive multimodality treatment (Fig 6).We thank John Orav, PhD, for his work on the statistics for this paper and Mary Sullivan Visciano for editorial assistance.

REFERENCES
1. Spirtas R, Beebe GW, Connelly RR, Wright WE, Peters JM,Sherwin RP, et al. Recent trends in mesothelioma incidence in the United States. Am J Ind Med 1986;9:397-407.
2. Connelly RR, Spirtas R, Myers MH, Percy CL, Fraumeni JF Jr.Demographic patterns for mesothelioma in the United States. J Natl Cancer Inst 1987;78:1053-60.
3. Enterline PE, Henderson VL. Geographic patterns of pleural mesothelioma deaths in the United States, 1968-81. J Natl Cancer Inst 1987;79:31-7.
4. Chahinian AP, Ambinder RM, Mandel EM, Holland JF.Evaluation of 63 patients with diffuse malignant mesothelioma[abstract]. Proc Am Soc Clin Oncol 1980;21:360.
5. Law MR, Hodson ME, Turner-Warwick M. Malignant mesothelioma of the pleura: clinical aspects and symptomatic treatment [abstract]. Eur J Respir Dis 1984;65:162-8.
6. Ruffie P, Feld R, Minkin S, et al. Diffuse malignant mesothelioma of the pleura in Ontario and Quebec: a retrospective study of 332 patients. J Clin Oncol 1989;7:1157-68.
7. Antman KH. Clinical presentation and natural history of benign and malignant mesothelioma. Semin Oncol 1981;8:313-20.
8. Baldini EH, Recht A, Strauss GM, DeCamp MM Jr, Swanson SJ,Liptay MJ, et al. Patterns of failure after trimodality therapy for malignant pleural mesothelioma. Ann Thorac Surg 1997;63:334-8.
9. Butchart EG, Ashcroft T, Barnsley WC, Holden MP. Pleuropneumonectomy in the management of diffuse malignant mesothelioma of the pleura: experience with 29 patients. Thorax 1976;31:15-24.
10. Antman K, Pass HI, Recht A. Benign and malignant mesothelioma.In: DeVita VT Jr, Hellman S, Rosenberg SA, editors.Cancer: principles and practice of oncology. 3rd ed. Philadelphia:JB Lippincott; 1989. p. 1399-414.
11. Antman KH, Pass HI, DeLaney T, Li FP, Corson J. Benign and malignant mesothelioma. In: DeVita VT Jr, Hellman S,Rosenberg SA, editors. Cancer: principles and practice of oncology.4th ed. Philadelphia: JB Lippincott; 1993. p. 1489-508.
12. Sugarbaker DJ, Mentzer SJ, DeCamp M, Lynch TJ Jr, Strauss GM. Extrapleural pneumonectomy in the setting of a multimodality approach to malignant mesothelioma. Chest 1993;103(suppl):377S-81S.
13. Sugarbaker DJ, Garcia JP, Richards WG, Harpole DH Jr, Baldini HE, DeCamp MM Jr, et al. Extrapleural pneumonectomy in the multimodality therapy of malignant pleural mesothelioma:results in 120 consecutive patients. Ann Surg 1996;224:288-94;
discussion.
14. Sugarbaker DJ, Strauss GM, Lynch TJ, Richards W, Mentzer SJ,Lee TH, et al. Node status has prognostic significance in the multimodality therapy of diffuse, malignant mesothelioma. J Clin Oncol 1993;11:1172-8.
15. Sugarbaker DJ, Mentzer SJ, Strauss G. Extrapleural pneumonectomy in the treatment of malignant pleural mesothelioma. Ann Thorac Surg 1992;54:941-6.
16. Rusch VW. A proposed new international TNM staging system for malignant pleural mesothelioma. From the International Mesothelioma Interest Group [see comments]. Chest 1995;108:1122-8.
17. Markman M, Kelsen D. Efficacy of cisplatin-based intraperitoneal chemotherapy as treatment of malignant peritoneal mesothelioma. J Cancer Res Clin Oncol 1992;118:547-50.
18. Krarup-Hansen A, Hansen HH. Chemotherapy in malignant mesothelioma: a review [abstract]. Cancer Chemother Pharmacol 1991;28:319-30.
19. Vogelzang NJ, Herndon J, Clamon GH, Mauer AM, Cooper MR,Green MR. Paclitaxel (Taxol) for malignant mesothelioma: a phase II study of the Cancer and Leukemia Group B (CALGB 9234) [abstract]. Prog Proc Am Soc Clin Oncol 1994;13:405:1382.
20. Herscher L, Hahn S, Pass H, Temeck B, Goldspiel B, Cook J, etal. A phase I study of paclitaxel as a radiation sensitizer for the treatment of non-small cell lung cancer and mesothelioma[abstract]. Prog Proc Am Soc Clin Oncol 1995;14:A1530.
21. Tolcher AW, Gelmon KA. Interim results of a phase I/II study of biweekly paclitaxel and cisplatin in patients with metastatic breast cancer. Semin Oncol 1995;22(4 Suppl 8):28-32.
22. Gelmon KA. Biweekly paclitaxel (Taxol) and cisplatin in breast and ovarian cancer. Semin Oncol 1994;21(5 Suppl 8):24-8.
23. Meerpohl HG, duBois A, Kuhnle H, Luck HJ, Kreienberg R,Mobus V, et al. Paclitaxel combined with carboplatin in the firstline treatment of advanced ovarian cancer. Semin Oncol 1995;22(6 Suppl 15):712.
24. Blois G. Pilot study with fixed-dose carboplatin and escalating paclitaxel in advanced ovarian cancer. Semin Oncol 1995;22(6suppl 14):32-4.
25. Belli L, LeChevalier T, Gottfried M, Adams D, Ruffie P, LeCesne A, et al. Phase I/II study of paclitaxel plus cisplatin as first-line chemotherapy for advanced non-small cell lung cancer: preliminary results. Semin Oncol 1995;22(6 Suppl 15):29-33.
26. Greco FA, Stroup SL, Hainsworth JD. Paclitaxel by 1-hour infusion in combination chemotherapy of stage III non-small cell lung cancer. Semin Oncol 1995;22(4 Suppl 9):75-7.
27. Muggia FM, Vafai D, Natale R, Israel V, Zaretsky S, McRae AM,et al. Paclitaxel 3-hour infusion given alone and combined with preliminary results of dose-escalation trials. Semin Oncol 1995;22(4 Suppl 9):63-6.
28. Strauss GM, Lynch TJ, Elias AD, Jacobs C, Kwiatkowski DJ,Shulman LN, et al. A phase I study of ifosfamide/carboplatin/etoposide/paclitaxel in advanced lung cancer. Semin Oncol 1995;22(4 Suppl 9):70-4.
29. Bunn PA Jr, Kelly K. A phase I study of carboplatin and paclitaxel in non-small cell lung cancer: a University of Colorado Cancer Center study. Semin Oncol 1995;22(4 Suppl 9):26.
30. Antonia SJ, Wagner H, Williams C, Alberts M, Hubbell D,Robinson L, et al. oncurrent paclitaxel/cisplatin with thoracic radiation in patients with stage IIIA/B non-small cell carcinoma of the lung. Semin Oncol 1995;22(4 Suppl 9):34-7.
31. Langer CJ, Leighton JC, Comis RL, O’Dwyer PJ, McAleer CA,Bonjo CA, et al. Paclitaxel by 24- or 1-hour infusion in combination with carboplatin in advanced non-small cell lung cancer:the Fox Chase Cancer Center experience. Semin Oncol 1995;
22(4 Suppl 9):18-29.
32. Chahinian AP, Mandeli JP, Gluck H, Naim H, Teirstein AS,Holland JF. Effectiveness of cisplatin, paclitaxel, and suramin against human malignant mesothelioma xenografts in athymic nude mice. J Surg Oncol 1998;67:104-11.
33. Griffiths CT, Grogan RH, Hall TC. Advanced ovarian cancer: primary treatment with surgery, radiotherapy, and chemotherapy.Cancer 1972; 29:1-7.
34. Sugarbaker PH. Observations concerning cancer spread within the peritoneal cavity and concepts supporting an ordered pathophysiology.In: Sugarbaker PH, editor. Peritoneal carcinomatosis:principles of management. Boston: Kluwer Academic Publishers;1996. p. 79-100.
35. Pass HI, DeLaney TF, Tochner Z, Smith PE, Temeck BK,Pogrebniak HW, et al.Intrapleural photodynamic therapy: results of a Phase I trial. Ann Surg Oncol 1994;1:28-37.
36. Pass HI, Temeck BK, Kranda K, Thomas G, Russo A, Smith P, etal. Phase III randomized trial of surgery with or without intraoperative photodynamic therapy and postoperative immunochemotherapy for malignant pleural mesothelioma. Ann Surg Oncol
1997;4:628-33.
37. Rusch V, Saltz L, Venkatraman E, Ginsberg R, McCormack P,Burt M, et al. A phase II trial of pleurectomy/decortication followed by intrapleural and systemic hemotherapy for malignant pleural mesothelioma. J Clin Oncol 1994:12:1156-63.
38. Rusch VW. Pleurectomy/decortication in the setting of multimodality
treatment for diffuse malignant pleural mesothelioma.Semin Thorac Cardiovasc Surg 1997;9:367-72.
39. Los G, vanVugt MJ, Pinedo HM. Potentiation of Ip chemotherapy by abdominal hyperthermia in rats [abstract]. Proc Ann Meet Am Assoc Cancer Res 1992:33:A2980.
40. Los G, Verdegaal EM, Mutsaers PH, McVie JG. Penetration of carboplatin and cisplatin into rat peritoneal tumor nodules after intraperitoneal chemotherapy. Cancer Chemother Pharmacol 1991;28:159-65.
41. Los G, McVie JG. Experimental and clinical status of intraperitoneal chemotherapy. Eur J Cancer 1990;26:775-62.
42. Jacquet P, Stephens AD, Averbach AM, Chang D, Ettinghausen SE, Dalton RR, et al. Analysis of morbidity and mortality in 60 patients with peritoneal carcinomatosis treated by cytoreductive surgery and heated intraoperative intraperitoneal chemotherapy.Cancer 1996;77:2622-9.
43. Kodama K, Doi O, Tatsuta M, Kuriyama K, Tateishi R.Development of postoperative intrathoracic chemo-thermotherapy for lung cancer with objective of improving local cure. Cancer 1989;64:1422-8.
Discussion Dr Larry R. Kaiser (Philadelphia, Pa). This series represents the largest series of extrapleural pneumonectomy todate. We have seen data from some of these patients in earlier studies but now have the advantage of looking at the mature data from 183 patients with a median follow-up inter val of 13 months. Amazingly, the overall operative mortality is a phenomenal 3.8%. This is truly impressive.
The data further support the functional staging classification originally proposed by Dr Sugarbaker and his colleagues and now further revised and updated, which further adds to the risk stratification and predictive value of this classification.
I would like to expand on what Dr Sugarbaker has already stated. Using his revised staging criteria, we can make betterinformed decisions regarding appropriate treatment for individual patients. Not all patients with mesothelioma are in a
hopeless condition. A significant percentage of patients deserve an aggressive multimodality approach, as the Brigham group has delineated.Dr Sugarbaker, to what do you attribute the absence of adult respiratory distress syndrome (ARDS) in this large
group of patients undergoing extrapleural pneumonectomy?Are you doing something we all should be doing?Obviously, patient selection is important. To what percentage
of patients with malignant pleural mesothelioma do you offer this multimodality approach?Do you have an arbitrary age cutoff, or is this individualized?
Are you performing mediastinoscopy routinely before resection?This is an aggressive regimen. Do you have any quality-oflife data from the first year of treatment? What percentage of patients have grade IV toxicity during the postoperative
chemotherapy-radiotherapy regimen?Did you find MRI predictive of which patients should be able to have at least a microscopically complete resection, if
not a complete resection? Can you base this on MRI criteria?Dr Sugarbaker. Thank you for your comments. I would like to start by addressing the question of ARDS. We did have some cases of ARDS, which contributed to the 25% morbidity.ARDS is seen in the same percentage that one would expect in patients undergoing pneumonectomy for non-small cell lung cancer.However, we have selected these patients via MRI, looking
for resectable disease, and by echocardiogram, and we do restrict intravenous fluids, probably not much different from our standard pneumonectomy patients. Nevertheless, I wonder what effect the screening for myocardial function would have on patients undergoing pneumonectomy in general. It may be helping, and it is an unseen benefit.
We do not have an age cutoff, but most of the patients whom we consider for this aggressive strategy are in their fifth or sixth decade. Surprisingly, we are seeing an increasing number of patients in their 40s and 50s with the disease. That does
make one reconsider possible new causes, such as the simian 40 virus, but we do not have any specific age cutoff.We seriously consider using this therapy in about one third of patients whom we see, so we see 3 or 4 for every single patient whom we consider for extrapleural pneumonectomy followed by trimodality therapy. In terms of mediastinoscopy, PET scanning, or laparoscopy to get at retro-aortic or etro-paraesophageal nodes, these are areas that need to be studied. Dr Rusch published a study on the use of laparoscopy to detect transdiaphragmatic involvement or intraperitoneal involvement, but I think we need to move forward with an evaluation of the ability of mediastinoscopy to detect nodal disease in these patients.Notice that we very carefully suggested that these were extrapleural nodes, and they are really a “grab bag” of mediastinal nodes, and that it is not clear how many of them would be accessible via mediastinoscopy. Nevertheless, I believe that
PET will be an interesting tool for pre-resectional staging.Patients with sarcomatous disease who have positive mediastinal nodes on mediastinoscopy should not be considered for aggressive therapy. Their survival is dismal despite an aggressive approach and the resectability rate is low.We do not have data on the quality of life in these individuals,but it is an important point and should be studied.
I do not have data on grade IV toxicity at hand. The reason we switched from the CAP protocol (cytoxan, Adriamycin,and then platinol), which was the most active ombination chemotherapy against mesothelioma, to carboplatin and paclitaxel was precisely because of the incidence of grade IV toxicity that prevented patients from completing the adjuvant regimen.We consider MRI to be a better pre-resectional staging modality than computed tomographic scanning, and we believe this has contributed significantly to the resectability rate in our patients, which now approaches 80%. It is indeed superior for looking at mediastinal invasion or transdiaphragmatic invasion.Dr G. Alexander Patterson (St Louis, Mo). That was a
great paper, Dr Sugarbaker. However, I do not understand why you are so light on the radiation. It seems to me that when local control is the issue, you emphasize surgery over radiation. I would have thought that 3000 rad was not quite consistent with the magnitude of the local control you are trying to achieve by that sort of an operation. How did you decide on that particular radiation regimen?Dr Sugarbaker. We arrived at that dose in a retrograde fashion. We began with 5500 rad, the maximal cytologic dose,to the ipsilateral hemithorax. When we combined that with
paclitaxel (Taxol) sensitization and the chemotherapy of carboplatin and paclitaxel, we found that a significant number of patients were becoming neutropenic from the amount of marrow that was being radiated. The dose can go as high as 4000
rad, and it really depends on the patient’s blood count, but a significant number of patients will become neutropenic from the amount of rib marrow that is being radiated.Dr L. Penfield Faber (Chicago, Ill). Dr Sugarbaker, this is an outstanding surgical series with a phenomenal mortality rate of 3.8%. Surgeons who have done extrapleural pneumonectomy for mesothelioma fully realize what an achievement
this is, as the earlier described mortality rates were much higher. The current mortality rate in our series at the Rush–Presbyterian–St Luke’s Medical Center is 7.5%.Having done extrapleural pneumonectomies and removed specimens that include the pleura, the pericardium, the lung,and the diaphragm, I find it difficult to understand what constitutes a negative microscopic margin. It can be technically
difficult to achieve a negative margin when removing the diaphragm from the inferior aspect of the posterior sulcus or at the apex of the chest along the innominate vein and subclavian vessels. You stated that this procedure is really a technique of cytoreduction, and it was implied that there may well be residual microscopic disease. It is difficult for me to comprehend where the microscopic margins are negative and also to understand how a surgical pathologist would evaluate and
dissect the specimen to identify negative microscopic margins.Please explain how negative microscopic margins are achieved with this diffuse malignant tumor.
My second question refers to the possible toxic manifestations of paclitaxel coupled with radiation. We have recently completed a pilot phase II study of neoadjuvant therapy for clinically advanced lung cancer using paclitaxel in combination
with radiation. We have observed significant complications after surgical resection when pretreating these patients with paclitaxel and radiation. Because of these complications,we no longer use paclitaxel in combination with radiation for
neoadjuvant therapy of lung cancer. I would appreciate hearing any comments you might have on the toxic manifestations of paclitaxel in your series.Dr Sugarbaker. I appreciate your comments. The issue of pathologic resection margins is an important one. The frustration that you outlined—where would you take your sample,how would you approach a specimen—led Dr Joseph Corson (professor of pathology at the Harvard Medical School, and chief of surgical pathology until last year at The Brigham and Women’s Hospital) to devise a systematic method some 9 years ago for assessing these specimens; his method involves systematically taking margins from 10 to 15 different points on the specimen, because trying to discern where the specimen looked positive and where it looked negative led to a nonsystematic appraisal.Dr Corson or his fellow takes the specimen, inks it, and lets us know exactly which of the sections is positive. I would emphasize that in evaluating the survival curves we are looking
at a marker of cytoreduction.I am not suggesting that we are rendering patients diseasefree.However, if you think of 10 to 15 sections and you begin to look at margins negative, margins positive, you are really looking at a quantification of how well your local control procedure accomplished what it set out to do.The most important lesson is that patients in whom we have achieved near-complete cytoreduction appear to have a survival advantage. This directs us toward local control strategies, such as heated intrathoracic chemotherapy at the time of resection, high-dose radiotherapy, photodynamic therapy, and some of the other areas that would be used against this particular tumor in its most vulnerable and most
lethal form, which is local recurrence.Last, I share your concern regarding paclitaxel radiotherapy.We have found that it is unsuccessful as neoadjuvant therapy
in mesothelioma. We have performed extensive surgery after induction therapy and have had a very high complication rate,which led us to abandon that form of treatment. Sometimes patients are referred who have already been treated. Those patients do not do well. Paclitaxel radiotherapy is still an open question. We have witnessed toxicity in conjunction with its use. As Dr Patterson elucidated, we have had to reduce our dose of radiotherapy to avoid toxicity in these patients.

Asbestos Lawyer Asbestos Attorney

Mesothelioma is a disease that has been on the rise over recent years. As cases of the disease have started to increase, lawyers dealing specifically with mesothelioma and asbestos lawsuits have come into operation. These lawyers and law firms deal, sometimes exclusively, with mesothelioma victims and their families who wish to claim compensation from the companies that were responsible for their exposure to asbestos. And mesothelioma lawsuits are often able to collect millions in compensation for the victims and their families.

Those who have been diagnosed with mesothelioma are entitled to file a lawsuit. Many of the companies responsible for exposing their employees to asbestos were well aware of the dangers and effects, but still saw fit to let their workers continue with little or no protection against the dust and fibers that emanated from this hazardous material. Now, decades later, the effects of this exposure is taking its toll on the workers just as they reach or are enjoying retirement. Quite rightly, the workers want to see justice done in the form of compensation, although this will never make up for the pain, suffering and loss of life that many of them have been sentenced to.

Many asbestos lawyers have dealt with numerous mesothelioma and asbestos lawsuits and have a good deal of experience and knowledge about the disease. Those looking for an asbestos lawyer should hunt around for someone that has proven experience in the field. Most reputable lawyers will be only too happy to provide facts and figures on pervious cases. They cannot, of course, name names and intricate details as this would be a breach of confidentiality. However, they can provide you with details on how quickly cases were resolved, how much compensation was successfully obtained and how many mesothelioma lawsuits they have dealt with.

There are many asbestos lawyers in operation today, and most people affected by asbestos will be able to find a local practicing asbestos lawyer. You should do a little research on successful cases as well as unsuccessful cases dealt with by the law firm that you are considering. This will enable you to make a more informed decision with regards to which asbestos lawyer you use for your case, based on the information provided by the lawyer or the law firm. It is important that you find a good, experienced asbestos lawyer as soon as possible after you have been diagnosed with an asbestos related disease such as mesothelioma. Most states have a set time limit in which you can file your lawsuit, and it is very important that you do not miss that deadline otherwise you may find that you are ineligible to make a claim.

When you go and seek assistance from an asbestos lawyer, don’t expect to get all the answers on day one. There is no way of predicting the direction in which your asbestos lawsuit might go, how quickly your case may be settled or how much you may get in compensation. Lawyers must assess each case on its own merits, and the course of action can be determined by any number of factors. However, there are some general guidelines available that could help you learn more about your legal options, and which should be discussed in greater detail with an asbestos lawyer or specialist.

It is useful for the asbestos lawyer if clients can provide as much information as possible with regards to their exposure, but this is not a necessity. Providing you are frank and open with the asbestos lawyer, the law firm can often hire someone to investigate your exposure to asbestos and will do this at no cost to you. And because most asbestos lawyers work on a contingency fee basis, you will pay nothing at all until you receive compensation, and nothing if your case is not successful.

Mesothelioma Settlements

With many mesothelioma cases coming to light each year, more and more people are coming forward to make their claim for compensation. As the number of sufferers of this disease increases, the number of law firms and lawyers that deal with and specialize in mesothelioma settlements also rises.

Although many have made a claim against the companies that exposed them to the hazardous asbestos and thus were responsible for the contraction of mesothelioma, the results of the claims can vary. Settlement figures have been known to differ dramatically, with some reaching seven figures.

Lawyers that deal with mesothelioma claims are not to be confused with the wide array of "no claim, no fee" lawyers that have sprung up in force over recent years. Many of these lawyers deal with anything from tripping up and falling over to falling off a dodgy chair. The law firm then takes a large chunk of whatever money you are awarded – if indeed you are awarded anything at all.

However, lawyers that deal with mesothelioma claims have a real purpose: to get you as much compensation as possible in order to provide security for your family when you are gone. And those that have been knowingly exposed to asbestos by irresponsible corporations have every right to claim this compensation, although it will never make up for the fact that they have ultimately been robbed of their lives.

With many mesothelioma settlements reaching their millions, new standards for compensation are being set continually. Sufferers of mesothelioma can now rest in the knowledge that not only will their medical bills be covered but their loved ones will be financially secure for the rest of their lives.

Those diagnosed with mesothelioma are more than entitled to log a claim for compensation. There are now many law firms worldwide that deal exclusively with mesothelioma cases, and they can not only work to get you a great settlement but can also offer support and advise to sufferers. Once you have logged your claim, a specialist can assess your case on its individual merits and can then contact you in order to discuss the details further.

Mesothelioma settlements are not only available to sufferers of the disease. Many law firms have secured substantial settlements for the families of those who have already died from asbestos-related mesothelioma. Since the cause and symptoms have only come to light in recent years, there was no facility for sufferers to claim until recently. But this does not mean that it is too late for the families of those that have already passed away. A claim can still be logged even after the patient has died, as the family is still entitled to compensation for the loss of their loved one.

Many lawyers offer free legal advice to mesothelioma patients, and the vast majority will not charge a penny unless they are successful in getting a financial settlement for the patient or family. Therefore, those who have been diagnosed with mesothelioma have nothing to lose by making a claim.

Depending on the location of the mesothelioma patient, there may be a limited time period in which a claim can be made. It is therefore important to contact a specialist lawyer as soon as a diagnosis has been made, otherwise you may lose your chance to make a valid claim.

You should check with a law firm with regards to the time limitations, and make sure that you take action as soon as possible in order to increase your chances of getting a settlement. If you are unsure as to the source of exposure, many law firms have investigative experts on hand who will do all of the necessary research and determine which company or companies were responsible for exposing you to asbestos.
When selecting a mesothelioma lawyer, patients should look for a firm with experience in dealing with similar cases. These firms may be able to give you an idea of how much your settlement could be, and will already have a lot of the information and resources to make a speedy start on processing your claim and getting your settlement finalized as soon as possible.

Filing a Mesothelioma Lawsuit

Many decades ago, when the effects of asbestos exposure became painfully apparent to manufacturers and users of this material, many companies made a very expensive mistake. They continued to use asbestos, exposing many employees to it on a daily basis. Many companies failed to tell their workers about the risks and hazards faced by this exposure, and simply let them continue their work and breathe in the asbestos dust. This was a mistake that was to cost these companies millions of dollars in years to come. Worse still, it was to cost many of their employees their lives.

Mesothelioma has a very long latency period, and it can be decades after the exposure to asbestos before the disease manifests itself. That’s why many people are now being diagnosed with mesothelioma after being exposed to asbestos thirty, forty, even fifty years ago. And with the diagnosis of the disease comes the right for the sufferer to file a lawsuit against the companies responsible for their death sentence.

There are a great many lawyers who now specialize in mesothelioma lawsuits, and many of them have been successful in obtaining multi-million dollar settlements for their clients. They encourage anyone that is diagnosed with mesothelioma to file a lawsuit, and will only take a fee if they are successful in securing compensation for the client.

However, mesothelioma patients must file their lawsuit almost immediately upon diagnosis. Many states have placed a time limit on filing a mesothelioma lawsuit, and is a claim is not made as soon as possible it may be too late. It is therefore important for sufferers to contact a specialist law firm and check how long they have to file their lawsuit.

For the families and loved ones of mesothelioma patients who have already passed away, the regulations are slightly different. However, the lawsuit must still be filed as soon as possible, and it is highly recommended that these families make contact with a suitably experienced lawyer as soon as possible.

You may also be eligible to file a lawsuit if you suffer from respiratory problems and are the close family member of someone who worked with asbestos. Because asbestos fibres and dust were often carried on the clothes of worker, this material often found its way into their homes thus exposing other family members to the dangers. It is quite possible that the family members could have contracted an asbestos-related disease even from this minimal exposure.

Whatever your connection with an asbestos-relates disease – whether you are a sufferer of mesothelioma, a family member who suffers from a related disorder, or a family member who is claiming on behalf of a deceased loved one – it is important that you look into filing your lawsuit as soon as possible to increase your chances of a successful settlement. There are many legal options which your lawyer will need to discuss with you in detail. In addition to this, the law firm may have to hire an investigator to determine when and where you or your loved one was exposed to asbestos. All this takes time, and with the time limitations that are set in most states, it means that you need to get the ball rolling as soon as you can.

Although it is impossible to say when you will receive a settlement, how much you will get, or even whether your lawsuit will be successful, all mesothelioma sufferers or their families are entitled to look into the matter of filing a lawsuit. With most lawyers working on a contingency fee basis – that is, a percentage of whatever your final settlement figure is – you will not need to worry about upfront costs or paying your lawyer if your lawsuit is unsuccessful.

By contacting an experienced mesothelioma lawyer at the earliest opportunity, you can discuss the various options and the lawyer will inform you of the viability of your lawsuit and whether you should proceed.

Mesothelioma Lawsuits: Frequently Asked Questions(FAQ)

Who has the right to file for compensation for mesothelioma?

A mesothelioma lawsuit can be filed by a person who has developed mesothelioma through exposure to asbestos. In the event that the person has passed away, the lawsuit can be filed by a family member or the executor of the deceased’s estate. A lawsuit can also be filed by a family member who has developed the disease through close contact with the person who was exposed to asbestos.

How long does the process take?

The process can take quite a while, although there is no set time and some lawyers will get your case sorted faster than others. The more research that is required to put a solid case together, the longer it will take.

How long do I have to file my claim?

This differs from state to state but generally the time limit is one to two years from diagnosis. It is important that you check on the time limitation for your state and act within the limitations otherwise you may not be eligible to claim. If you are claiming on behalf of the deceased, time limitations still apply and it is probably even more important to act quickly because of the time limits and the research required by the lawyer.


What if I don’t know where and when I was exposed to asbestos?

It is helpful if you know this and will certainly speed up the process, but if you don’t remember the lawyer will be able to help. A private investigator can be hired through the lawyer (paid for by the lawyer) who will do the necessary research to clarify when and where the exposure took place and which company or companies are responsible.

How can I afford legal assistance?

You won’t need to worry about having cash up front because mesothelioma lawyers usually work on a no win no fee basis. You will not have to pay a penny unless you receive compensation, and then the lawyer will take a percentage of the compensation as his fee.

How much will I get?

It’s impossible to say how much you will get as it depends on the merits of your case. Your lawyer will discuss this with you in more detail when you go through the details of your claim, but past settlements have notched up hundred of thousands of dollars and even multi-million dollar payouts.

Where can I find a mesothelioma lawyer?

There are now many mesothelioma lawyers and you should have no problem finding one. The Internet is a good place to start your search, as many mesothelioma lawyers advertise there. You can check out many credentials and assess the experience of individual law firms by searching on the Internet. You can also submit your details via the Internet in many cases, allowing the law firm to evaluate your case and then contact you. You can also check in your local phone directory for details of mesothelioma lawyers. However, try to find a lawyer that has experience of working with mesothelioma lawsuits as they will already have a network of resources and contact that could help to process your case more quickly.

Will the lawsuit be filed in the state where I live?

Not necessarily. Your lawyer will select the state in which you have the best chance of success and where you are likely to get the highest compensation. This will make no difference to you as you will not have to pay any extra and may end up getting far more compensation in another state.

Will my case go to court?
Again, it is impossible to say until your lawyer has tried to settle out of court. However, most mesothelioma cases are settled out of court and this saves both sides money because taking the case to court can get costly.

Mesothelioma Legal Options: Frequently Asked Questions(FAQ)

Am I entitled to file a lawsuit if I think I have been affected by asbestos?

You can only file a law suit if you have definitely been affected by asbestos, which means seeking medical assistance and getting a diagnosis of mesothelioma as soon as possible. Once your diagnosis has been confirmed by your doctor, you should then seek legal assistance as soon as possible to file your lawsuit for compensation. Your lawyer will need to have details of your diagnosis in order to put together your law suit.
Who will I be suing?

This all depends on your situation and where, when and how you were exposed to asbestos. You may have been exposed by your employer many years ago; your exposure may have been the result of a faulty product that contains asbestos; or you may have been exposed through contact with someone that worked with asbestos. Your lawyer will advise you on the best route to take with your compensation claim.
Can doctors be sued for not diagnosing the disease quickly enough?

Although cases have been filed for medical negligence, this is a tricky area. Because the disease takes so long to properly manifest, it is often at quite a late stage by the time you seek medical assistance and a diagnosis is made. Furthermore, the symptoms of mesothelioma are very non-specific which means that they could be associated with a number of other common diseases. If your doctor is not aware of your connection with asbestos, there is a good chance that he or she will test and treat your for a number of other diseases before testing for mesothelioma. To avoid this happening, you should always make your doctor aware that you have been exposed to asbestos, as this will give him the information he needs to make an informed diagnosis and prescribe early treatment.

What does the compensation cover?

The compensation you receive is to cover a number of things. Firstly, you may have run up enormous medical bills getting tests and treatment for your illness. Secondly, you have every right to be compensated for the pain and suffering you have experienced as well as the mental anguish and grief suffered by yourself and your family. And thirdly, your family has a right to be financially secure after you have gone, and the companies responsible for your terminal illness should be liable to pay for this financial security.

Is my lawsuit guaranteed to be successful?

There are no guarantees, but providing you find a lawyer as soon as possible (within the time limits set by your state) and you are able to help your lawyer put a good case together by providing the necessary information a quickly as possible, then you stand a good chance.

Will a lawyer charge much for his services?

The good news is that most mesothelioma lawyers will not charge any up front fees at all. Even if they have to hire an investigator to do some research to help your case, they normally foot the bill for this. These lawyers work on a contingency fee, which means that the only money they take is from your compensation payout if and when you are successful. No compensation for you means no fee for the lawyer. If you do get compensation, the lawyer does take a cut as his fee – normally around 35%.

What if I have missed the deadline within which I can file a claim?

You must always seek legal advice within the statutes of limitation as according to your state, as this will maximise your chances of a successful lawsuit. However, if for any reason you have missed the deadline, there is no harm in contacting a lawyer anyway to see whether there is anything that can be done. Your lawyer may have an idea of how to get around this, but a missed deadline normally means that your chances of success are slim

Getting Compensation for Mesothelioma

Why are mesothelioma sufferers entitled to compensation?

The danger of working with asbestos on a regular basis has been known to many companies and manufacturers for decades. However, these companies still let their oblivious employees work with this material without protection, putting their health at risk for mesothelioma without their knowledge. And now, decades later, many of these employees are discovering that they have a terminal illness because of this exposure, and instead of enjoying retirement they are subjected to medication, pain, misery and death.

Because of the long latency period of the asbestos related cancer, mesothelioma, these employees have no idea that they have the disease until thirty or forty years after their exposure. And then, as the symptoms of the disease start to manifest, they seek medical help and are finally told that they have a cancer that was caused by asbestos many years ago.

This is devastating news for both the victim and his or her family.

The compensation that mesothelioma sufferers are eligible to file for is to cover this pain, suffering and mental anguish, as well as to cover medical expenses which can be crippling with the number of tests and treatments that are often required. Another reason for the compensation is to secure the future of the family after the victim has passed away. The typical survival time for a patient with malignant mesothelioma is from four to twelve months, which means that the family may not only have to handle the dreadful news about the disease but also handle their loved one being taken from them shortly after.
How mesothelioma claims are made and settled:

To file your claim for compensation, you must act quickly. A lot of work may be required in order to put a solid case together and there are certain time limits within which action must be taken, which vary from state to state. You should check on these time limits (known as statutes of limitation) and then set about finding a lawyer. Look for a lawyer who is experienced in dealing with mesothelioma cases as this could make things both easier and faster due to the pool of contacts and resources the lawyer probably already has.

Once your lawyer has discussed your case fully, he will advise you on your options. If he feels that the case is solid and worth pursuing, you will need to provide details on when and where you may have been exposed to asbestos so that the culprit can be identified. If you cannot do this, the lawyer will hire someone to do the necessary research and find out. Once all the details have been obtained, your lawyer will try and settle your case out of court. This benefits all parties because it can save a huge amount on legal costs and does not tend to drag on for years as court cases can.

The amount awarded will depend on a number of factors such as the type of mesothelioma you have been diagnosed with and to what degree you have been affected medically. Many victims have claimed millions of dollars in compensation, securing the future of their families as well as covering pain, suffering and medical expenses. When you initially discuss you case with the lawyer he may be able to give you an idea of the amount that others in your situation received – another advantage of selecting an experienced lawyer.

Once your compensation is agreed and paid out, your lawyer will take a percentage as his fee. You will not have to pay any up front costs for legal assistance, so if for any reason you are not compensated you will not be liable for any costs whatsoever. With this in mind, anyone that has been medically affected by asbestos exposure in this way should have no hesitation in filing a lawsuit because they have nothing to lose. If there is no compensation paid, they are no worse off. And if a compensation claim is successful they could secure their families financial future.
Time is of the essence if you are planning to file a mesothelioma lawsuit and you should always bear this in mind. But providing you seek timely advice and file your claim as soon as possible, you stand a good chance of getting the compensation you deserve; whether it is thousands of dollars or tens, if not hundreds, of millions.

Mesothelioma And The Law

Over recent years, we have seen many multi-million dollar compensation payouts to victims of mesothelioma, the asbestos exposure related cancer. This is a relatively new disease, both in terms of medical and legal awareness, and sufferers of mesothelioma are finding that they are entitled to a hefty compensation in many cases. And to help these victims get their dues, many lawyers and law firms have been trained and set up to deal with mesothelioma claims in order to get mesothelioma sufferers the compensation to which they are entitled.

Why are mesothelioma victims entitled to compensation? Well, most cancers not the fault of an outsider. Heavy smokers may get cancer through smoking, which is their own choice. Other types of cancer, such as breast, cervical and prostate are not anybody’s fault, although vigilance and regular check ups can help to identify these caners early on and therefore treat them effectively. However, mesothelioma is a totally different type of cancer. This is a cancer that could have been prevented, and it is the fault of outsiders – namely the irresponsible firms that made no efforts to protect their workers against the hazards of working with asbestos. You see, mesothelioma is the result of regular exposure the asbestos dust and fibres, which are ingested into the system and corrupt the cells of the protective lining that surround major organs – the mesothelium. The cancer lies dormant for many decades, and victims do not realise until thirty or forty years later that they have the disease. By the time tests have been done and a diagnosis has been made, it is often too late to do anything constructive about it, and the patient is left with just a short time to live – typically 4-24 months.

These mesothelioma lawyers are here to help victims of mesothelioma to get cold, hard cash from the companies responsible for their doomed fate. This compensation will help to cover medical expenses and pain and suffering. But, perhaps most importantly, it helps to provide financial stability and security for the victim’s loved ones after he or she has passed away.

The payouts for mesothelioma lawsuits have run from hundreds of thousands of dollars, to multi-million dollars. But the mesothelioma sufferer must ensure that the chances of success are optimised by seeking legal advice and assistance as soon as the diagnosis has been confirmed. Most states only provide a certain time within which you can file a mesothelioma lawsuit, so it is vital that you do this immediately. Your lawyer will also need the extra time to put your case together and carry out any necessary research. Time is of the essence where mesothelioma lawsuits are concerned, and just a few days could make the difference between financial security for your family and no compensation at all.

If you are concerned about not having any money up-front to pay for legal costs, don’t be. The vast majority of mesothelioma lawyers work on a contingency fee basis. This means that they do not take any money from you up-front. And if your case is unsuccessful they will not take any money from you at all. You only have to pay the lawyer if and when you receive compensation. Your lawyer will then be entitled to a percentage of the compensation. And, although the cut to which the lawyer is entitled can seem high – generally around the 35% mark – it does mean that you don’t have to worry about paying in order to file for compensation and you have nothing to lose if you don’t get any compensation.
Your mesothelioma lawyer will also be able to give you support and advice with regards to your illness. The experienced mesothelioma lawyers have already built up a network of contacts within the field; not only for legal support but for all types of support and advice. This network means that your lawyer can process your claim more quickly than a lawyer who has little or no knowledge or experience in dealing with mesothelioma lawsuits. The experienced lawyer will also be able to point you in the right direction for additional support services and support groups

Questions to ask when selecting a mesothelioma attorney.

These pages provide consumer tips for how to deal with the financial aspects of selecting a mesothelioma attorney. They do not provide any information regarding the medical aspects of this serious disease.

Since so much is at stake, selecting the right mesothelioma lawyer is very important. According the Wall Street Journal, lawyers say a typical mesothelioma award in a mesothelioma settlement is $1 million, and attorneys get 40% of this amount. If the case actually goes to trial, the average award was $6 million in 2001, which was triple the amount awarded just two years earlier.

So, mesothelioma attorneys are very eager to find mesothelioma patients. And it's vital that patients select the mesothelioma attorneys that are best for them.

A Brief Background on Your Legal Rights Regarding Mesothelioma

Companies that manufacture products that contain asbestos have known for over 60 years that asbestos can cause serious diseases.

Unfortunately, because many of these companies wanted to increase their profits, they kept this information quiet, thereby seriously endangering their workers.

There are now laws that help protect the workers who have been harmed by their exposure to these asbestos-related products.

However, since representing mesothelioma can be so profitable to attorneys, it is important that people who have mesothelioma be especially careful selecting attorneys who are really qualified to represent them. Therefore, we have created a list of...
Important Questions to Ask When Selecting a Mesothelioma Attorney

Question #1 to Ask When Selecting a Mesothelioma Attorney:

What is your personal experience in representing mesothelioma patients? Your goal is to find out how many cases the attorney has actually handled.

You also want to know: how many of these were settled, and how many of these went to trial? What were the results of each case?

You should ask the same questions about his or her law firm. You're goal is to find out about the firm -- is this an area the firm specializes in?

Question #2 to Ask When Selecting a Mesothelioma Attorney:

Next, you want to ask if the lawyer intends to actually handle your case him or herself. Many attorneys simply refer these cases to another law firm and receive part of the fee in exchange. This may not be in your best interest.

Mesothelioma risks and causes

Mesothelioma is quite a rare cancer but it is becoming more common. Just over 2,100 people were diagnosed with mesothelioma in the UK in 2003. There are about 4 times as many cases in men as in women. This is probably because many cases have been caused by exposure to asbestos at work. Pleural mesothelioma is much more common than peritoneal mesothelioma. This page is about the risk factors and possible causes of mesothelioma. You can scroll down the page to read all the information here. Or you can use these links to go straight to sections on

* Asbestos and mesothelioma
* What is asbestos?
* How does asbestos cause mesothelioma?
* Radiation
* Other chemicals
* A virus called SV40

Asbestos and mesothelioma

Unusually for cancer, we do know what causes the majority of cases of mesothelioma. It is most often linked to exposure to asbestos. We have known of a link between asbestos and lung disease since the beginning of the 18th century. But the link with mesothelioma has only been known since the 1960's. Unfortunately, the number of cases of mesothelioma in the UK each year is expected to rise sharply over the next 20 years because of the heavy use of asbestos in industry from the end of the second world war up until the mid 1970s.

Between 7 and 8 out of every 10 people (70–80%) diagnosed with mesothelioma say they have been in contact with asbestos. Your risk is greater if you were exposed to large amounts of it from an early age for a very long period of time. But there are some patients that say they have no history of any heavy exposure to asbestos.

Remember: Many people who develop mesothelioma due to asbestos exposure may be eligible for compensation. You should talk to a solicitor about this as early as possible. Your specialist doctor or nurse may be able to give you some information on this from their dealings with other mesothelioma patients. Or some of the mesothelioma organisations in Help and Support should be able to help.

What is asbestos?
Asbestos is an insulating material that is heat and fire resistant. In the past, asbestos was used widely in the

* Building industry
* Ship building industry
* Manufacture of household appliances
* Motor industry
* Power stations
* Telephone exchanges

So most cases of mesothelioma occur in men who have worked in manufacturing using asbestos or used asbestos products, particularly in construction or engineering. The use of asbestos was very heavy in the years after the war (after 1945). Mesothelioma may not develop until 15 - 40 years after you have been exposed to asbestos, which is why we are seeing an increase in cases now. The number of cases is expected to peak around 2020 and then start to decline.

There are three main types of asbestos: blue, brown and white. Blue and brown asbestos are strongly linked with mesothelioma. They have been banned since the late 1980's and cannot be imported into the UK. White asbestos is now also thought to be harmful. The use of all asbestos was banned in 1999 in the UK.

How does asbestos cause mesothelioma?

Asbestos is made up of tiny fibres. You can breathe these fibres in when you come into contact with asbestos. The fibres work their way into the pleura, lining the lung. They irritate the pleura and damage the cells that the pleura are made of. Some of the fibres that have been breathed in can be coughed up and swallowed. This is probably the cause of peritoneal mesothelioma.

If you have been exposed to asbestos, your family may also have been exposed. Asbestos fibres can be carried home on your clothes. Research studies have confirmed that the family of people exposed to asbestos also have a higher risk of developing mesothelioma.

Radiation

Pleural and peritoneal mesothelioma has been known to develop after exposure to a type of radiation called thorium dioxide (Thorotast). This was used until the 1950's in some X-ray tests.

Other chemicals

A mineral found in Turkey called Zeolite may cause mesothelioma.

The SV40 virus

There has been some research into a virus called SV40 (the SV stands for 'simian virus'). There is a lot of dispute amongst scientists about this and it isn't generally accepted as a cause. It seems more likely that the virus doesn't cause mesothelioma. It is possible that SV40 may help to increase risk if you've been exposed to another more major risk factor. Doctors call this a 'co-factor'. But SV40 certainly hasn't been proved to be a co-factor so far. In any case, it is far less important a risk factor than asbestos.

Mesothelioma: Questions and Answers

# What is the mesothelium?

The mesothelium is a membrane that covers and protects most of the internal organs of the body. It is composed of two layers of cells: One layer immediately surrounds the organ; the other forms a sac around it. The mesothelium produces a lubricating fluid that is released between these layers, allowing moving organs (such as the beating heart and the expanding and contracting lungs) to glide easily against adjacent structures.

The mesothelium has different names, depending on its location in the body. The peritoneum is the mesothelial tissue that covers most of the organs in the abdominal cavity. The pleura is the membrane that surrounds the lungs and lines the wall of the chest cavity. The pericardium covers and protects the heart. The mesothelial tissue surrounding the male internal reproductive organs is called the tunica vaginalis testis. The tunica serosa uteri covers the internal reproductive organs in women.

# What is mesothelioma?

Mesothelioma (cancer of the mesothelium) is a disease in which cells of the mesothelium become abnormal and divide without control or order. They can invade and damage nearby tissues and organs. Cancer cells can also metastasize (spread) from their original site to other parts of the body. Most cases of mesothelioma begin in the pleura or peritoneum.

# How common is mesothelioma?

Although reported incidence rates have increased in the past 20 years, mesothelioma is still a relatively rare cancer. About 2,000 new cases of mesothelioma are diagnosed in the United States each year. Mesothelioma occurs more often in men than in women and risk increases with age, but this disease can appear in either men or women at any age.

# What are the risk factors for mesothelioma?

Working with asbestos is the major risk factor for mesothelioma. A history of asbestos exposure at work is reported in about 70 percent to 80 percent of all cases. However, mesothelioma has been reported in some individuals without any known exposure to asbestos.

Asbestos is the name of a group of minerals that occur naturally as masses of strong, flexible fibers that can be separated into thin threads and woven. Asbestos has been widely used in many industrial products, including cement, brake linings, roof shingles, flooring products, textiles, and insulation. If tiny asbestos particles float in the air, especially during the manufacturing process, they may be inhaled or swallowed, and can cause serious health problems. In addition to mesothelioma, exposure to asbestos increases the risk of lung cancer, asbestosis (a noncancerous, chronic lung ailment), and other cancers, such as those of the larynx and kidney.

Smoking does not appear to increase the risk of mesothelioma. However, the combination of smoking and asbestos exposure significantly increases a person’s risk of developing cancer of the air passageways in the lung.

# Who is at increased risk for developing mesothelioma?

Asbestos has been mined and used commercially since the late 1800s. Its use greatly increased during World War II. Since the early 1940s, millions of American workers have been exposed to asbestos dust. Initially, the risks associated with asbestos exposure were not known. However, an increased risk of developing mesothelioma was later found among shipyard workers, people who work in asbestos mines and mills, producers of asbestos products, workers in the heating and construction industries, and other tradespeople. Today, the U.S. Occupational Safety and Health Administration (OSHA) sets limits for acceptable levels of asbestos exposure in the workplace. People who work with asbestos wear personal protective equipment to lower their risk of exposure.

The risk of asbestos-related disease increases with heavier exposure to asbestos and longer exposure time. However, some individuals with only brief exposures have developed mesothelioma. On the other hand, not all workers who are heavily exposed develop asbestos-related diseases.

There is some evidence that family members and others living with asbestos workers have an increased risk of developing mesothelioma, and possibly other asbestos-related diseases. This risk may be the result of exposure to asbestos dust brought home on the clothing and hair of asbestos workers. To reduce the chance of exposing family members to asbestos fibers, asbestos workers are usually required to shower and change their clothing before leaving the workplace.

# What are the symptoms of mesothelioma?

Symptoms of mesothelioma may not appear until 30 to 50 years after exposure to asbestos. Shortness of breath and pain in the chest due to an accumulation of fluid in the pleura are often symptoms of pleural mesothelioma. Symptoms of peritoneal mesothelioma include weight loss and abdominal pain and swelling due to a buildup of fluid in the abdomen. Other symptoms of peritoneal mesothelioma may include bowel obstruction, blood clotting abnormalities, anemia, and fever. If the cancer has spread beyond the mesothelium to other parts of the body, symptoms may include pain, trouble swallowing, or swelling of the neck or face.

These symptoms may be caused by mesothelioma or by other, less serious conditions. It is important to see a doctor about any of these symptoms. Only a doctor can make a diagnosis.

# How is mesothelioma diagnosed?

Diagnosing mesothelioma is often difficult, because the symptoms are similar to those of a number of other conditions. Diagnosis begins with a review of the patient’s medical history, including any history of asbestos exposure. A complete physical examination may be performed, including x-rays of the chest or abdomen and lung function tests. A CT (or CAT) scan or an MRI may also be useful. A CT scan is a series of detailed pictures of areas inside the body created by a computer linked to an x-ray machine. In an MRI, a powerful magnet linked to a computer is used to make detailed pictures of areas inside the body. These pictures are viewed on a monitor and can also be printed.

A biopsy is needed to confirm a diagnosis of mesothelioma. In a biopsy, a surgeon or a medical oncologist (a doctor who specializes in diagnosing and treating cancer) removes a sample of tissue for examination under a microscope by a pathologist. A biopsy may be done in different ways, depending on where the abnormal area is located. If the cancer is in the chest, the doctor may perform a thoracoscopy. In this procedure, the doctor makes a small cut through the chest wall and puts a thin, lighted tube called a thoracoscope into the chest between two ribs. Thoracoscopy allows the doctor to look inside the chest and obtain tissue samples. If the cancer is in the abdomen, the doctor may perform a peritoneoscopy. To obtain tissue for examination, the doctor makes a small opening in the abdomen and inserts a special instrument called a peritoneoscope into the abdominal cavity. If these procedures do not yield enough tissue, more extensive diagnostic surgery may be necessary.

If the diagnosis is mesothelioma, the doctor will want to learn the stage (or extent) of the disease. Staging involves more tests in a careful attempt to find out whether the cancer has spread and, if so, to which parts of the body. Knowing the stage of the disease helps the doctor plan treatment.

Mesothelioma is described as localized if the cancer is found only on the membrane surface where it originated. It is classified as advanced if it has spread beyond the original membrane surface to other parts of the body, such as the lymph nodes, lungs, chest wall, or abdominal organs.

# How is mesothelioma treated?

Treatment for mesothelioma depends on the location of the cancer, the stage of the disease, and the patient’s age and general health. Standard treatment options include surgery, radiation therapy, and chemotherapy. Sometimes, these treatments are combined.

* Surgery is a common treatment for mesothelioma. The doctor may remove part of the lining of the chest or abdomen and some of the tissue around it. For cancer of the pleura (pleural mesothelioma), a lung may be removed in an operation called a pneumonectomy. Sometimes part of the diaphragm, the muscle below the lungs that helps with breathing, is also removed.

* Radiation therapy, also called radiotherapy, involves the use of high-energy rays to kill cancer cells and shrink tumors. Radiation therapy affects the cancer cells only in the treated area. The radiation may come from a machine (external radiation) or from putting materials that produce radiation through thin plastic tubes into the area where the cancer cells are found (internal radiation therapy).

* Chemotherapy is the use of anticancer drugs to kill cancer cells throughout the body. Most drugs used to treat mesothelioma are given by injection into a vein (intravenous, or IV). Doctors are also studying the effectiveness of putting chemotherapy directly into the chest or abdomen (intracavitary chemotherapy).

To relieve symptoms and control pain, the doctor may use a needle or a thin tube to drain fluid that has built up in the chest or abdomen. The procedure for removing fluid from the chest is called thoracentesis. Removal of fluid from the abdomen is called paracentesis. Drugs may be given through a tube in the chest to prevent more fluid from accumulating. Radiation therapy and surgery may also be helpful in relieving symptoms.

# Are new treatments for mesothelioma being studied?

Yes. Because mesothelioma is very hard to control, the National Cancer Institute (NCI) is sponsoring clinical trials (research studies with people) that are designed to find new treatments and better ways to use current treatments. Before any new treatment can be recommended for general use, doctors conduct clinical trials to find out whether the treatment is safe for patients and effective against the disease. Participation in clinical trials is an important treatment option for many patients with mesothelioma.

People interested in taking part in a clinical trial should talk with their doctor. Information about clinical trials is available from the Cancer Information Service (CIS) (see below) at 1–800–4–CANCER. Information specialists at the CIS use PDQ®, NCI’s cancer information database, to identify and provide detailed information about specific ongoing clinical trials. Patients also have the option of searching for clinical trials on their own. The clinical trials page on the NCI’s Cancer.gov Web site, located at http://www.cancer.gov/clinical_trials on the Internet, provides general information about clinical trials and links to PDQ.

People considering clinical trials may be interested in the NCI booklet Taking Part in Clinical Trials: What Cancer Patients Need To Know. This booklet describes how research studies are carried out and explains their possible benefits and risks. The booklet is available by calling the CIS, or from the NCI Publications Locator Web site at http://www.cancer.gov/publications on the Internet.

Signs and symptoms

Symptoms of mesothelioma may not appear until 20 to 50 years after exposure to asbestos. Shortness of breath, cough, and pain in the chest due to an accumulation of fluid in the pleural space are often symptoms of pleural mesothelioma.

Symptoms of peritoneal mesothelioma include weight loss and cachexia, abdominal swelling and pain due to ascites (a buildup of fluid in the abdominal cavity). Other symptoms of peritoneal mesothelioma may include bowel obstruction, blood clotting abnormalities, anemia, and fever. If the cancer has spread beyond the mesothelium to other parts of the body, symptoms may include pain, trouble swallowing, or swelling of the neck or face.

These symptoms may be caused by mesothelioma or by other, less serious conditions.

Mesothelioma that affects the pleura can cause these signs and symptoms:

* chest wall pain
* pleural effusion, or fluid surrounding the lung
* shortness of breath
* fatigue or anemia
* wheezing, hoarseness, or cough
* blood in the sputum (fluid) coughed up

In severe cases, the person may have many tumor masses. The individual may develop a pneumothorax, or collapse of the lung. The disease may metastasize, or spread, to other parts of the body.

Tumors that affect the abdominal cavity often do not cause symptoms until they are at a late stage. Symptoms include:

* abdominal pain
* ascites, or an abnormal buildup of fluid in the abdomen
* a mass in the abdomen
* problems with bowel function
* weight loss

In severe cases of the disease, the following signs and symptoms may be present:

* blood clots in the veins, which may cause thrombophlebitis
* disseminated intravascular coagulation, a disorder causing severe bleeding in many body organs
* jaundice, or yellowing of the eyes and skin
* low blood sugar level
* pleural effusion
* pulmonary emboli, or blood clots in the arteries of the lungs
* severe ascites

A mesothelioma does not usually spread to the bone, brain, or adrenal glands. Pleural tumors are usually found only on one side of the lungs.