Mesothelioma. 1. Introduction. 1.1 General Information and Aetiology

Similar documents
Rare Thoracic Tumours

Malignant Mesothelioma

Malignant Mesothelioma

بسم هللا الرحمن الرحيم

Clinical cases in Malignant Pleural Mesothelioma: Adherence to the ESMO Clinical Practice Guidelines

Survey of Mesothelioma Associated with Asbestos Exposure in Japan

Summary of treatment benefits

L Lang-Lazdunski, A Bille, S Marshall, R Lal, D Landau, J Spicer

Mesothelioma: Questions and Answers

Malignant Pleural Mesothelioma in Singapore

Extrapleural Pneumonectomy for Malignant Mesothelioma: Pro. Joon H. Lee 9/17/2012

Malignant pleural mesothelioma P/D vs. EPP

INTERNATIONAL ASSOCIATION FOR THE STUDY OF LUNG CANCER Prospective Mesothelioma Staging Project

Lung Cancer. Public Outcomes Report. Submitted by Omar A. Majid, MD

B10/S/a Cancer: Malignant Mesothelioma (Adult)

Recommendations for the Reporting of Pleural Mesothelioma

Malignant Mesothelioma: an Update

Sternotomy and removal of the tumor

Malignant Mesothelioma State of the Art

Understanding Pleural Mesothelioma

Round Table with Drs. Anne Tsao and Alex Farivar, Case 2: Mesothelioma

Update on Mesothelioma

MesoPDT. Photodynamic Therapy for malignant pleural mesothelioma ONCO-THAI. Image Assisted Laser Therapy for Oncology

Accelerated hemithoracic radiation followed by extrapleural pneumonectomy for malignant pleural mesothelioma

Mesothelioma , The Patient Education Institute, Inc. ocft0101 Last reviewed: 03/21/2013 1

Seton Medical Center Hepatocellular Carcinoma Patterns of Care Study Rate of Treatment with Chemoembolization N = 50

How To Treat Mesothelioma

What is Mesothelioma?

Lung Cancer Treatment Guidelines

Mesothelioma. Malignant Pleural Mesothelioma

J of Evidence Based Med & Hlthcare, pissn , eissn / Vol. 2/Issue 33/Aug. 17, 2015 Page 5063

Asbestos Related Diseases

Screening, early referral and treatment for asbestos related cancer

Clinical Indications and Results Following Chest Wall Resection

Disease/Illness GUIDE TO ASBESTOS LUNG CANCER. What Is Asbestos Lung Cancer? Telephone

Treatment Algorithms for the Management of Lung Cancer in NSW Guide for Clinicians

Epidemiology, Staging and Treatment of Lung Cancer. Mark A. Socinski, MD

Malignant Mesothelioma

Adjuvant Therapy Non Small Cell Lung Cancer. Sunil Nagpal MD Director, Thoracic Oncology Jan 30, 2015

Surgical therapy of. who should be operated

Objectives. Mylene T. Truong, MD. Malignant Pleural Mesothelioma Background

Surgery. Wedge resection only part of the lung, not. not a lobe, is removed. Cancer Council NSW

Malignant Mesothelioma

Targeting Specific Cell Signaling Pathways for the Treatment of Malignant Peritoneal Mesothelioma

MESOTHELIOMA. Not Just a Late Night Commercial. Graciela Hoal, RN, MSN, ACNP-BC

Asbestos Related Diseases. Asbestosis Mesothelioma Lung Cancer Pleural Disease. connecting raising awareness supporting advocating

Asbestos and your lungs

How To Treat Lung Cancer At Cleveland Clinic

Surgeons Role in Symptom Management. A/Prof Cliff K. C. Choong Consultant Thoracic Surgeon Latrobe Regional Hospital GIPPSLAND

Lung cancer forms in tissues of the lung, usually in the cells lining air passages.

GUIDELINES FOR THE MANAGEMENT OF LUNG CANCER

Lung Cancer: Diagnosis, Staging and Treatment

1 page Overview. CONCURRENT 1D, 1E, 1F Biology & Pathogenesis Multi-Modality Immunology 1

How To Understand How Cancer Works

Please see the LUCADA data manual v3.1.3, available in the downloads section

Treatment of mesothelioma in Bloemfontein, South Africa

Lessons learned from the Western Australian experience with mesothelioma

Pre-workshop exercise

Lung Cancer and Mesothelioma

Research Article Frequency of Surgery in Black Patients with Malignant Pleural Mesothelioma

Non-Small Cell Lung Cancer Treatment Comparison to NCCN Guidelines

The lungs What is lung cancer? How common is it? Risks & symptoms Diagnosis & treatment options

PROTOCOL OF THE RITA DATA QUALITY STUDY

Lung Cancer. This reference summary will help you better understand lung cancer and the treatment options that are available.

Rotation Specific Goals & Objectives: University Health Network-Princess Margaret Hospital/ Sunnybrook Breast/Melanoma

Management of Non-Small Cell Lung Cancer Guide for General Practitioners

Malignant Mesothelioma Current Approaches to a Difficult Problem. Raja M Flores, MD Thoracic Surgery Memorial Sloan-Kettering Cancer Center

The Need for Accurate Lung Cancer Staging

Lung Cancer & Mesothelioma

Malignant pleural mesothelioma: outcome of limited surgical management

Treating Mesothelioma - A Quick Guide

Primary -Benign - Malignant Secondary

REPORT PERSPECTIVES IN LUNG CANCER 2010 AMSTERDAM

Avastin: Glossary of key terms

Neoplasms of the LUNG and PLEURA

International Journal of Case Reports in Medicine

Small Cell Lung Cancer

A Practical Guide to Advances in Staging and Treatment of NSCLC

Malignant Pleural Diseases Advances Clinicians Should Know F Gleeson

The National Clinical Lung Cancer Audit (LUCADA)

Small cell lung cancer

SMALL CELL LUNG CANCER

FREQUENTLY ASKED QUESTIONS about asbestos related diseases

A Case of Advanced Malignant Pleural Mesothelioma Treatment with Chemotherapy and Photodynamic Therapy

Occupational respiratory diseases due to Asbestos. Dirk Dahmann, IGF, Bochum

Komorbide brystkræftpatienter kan de tåle behandling? Et registerstudie baseret på Danish Breast Cancer Cooperative Group

2015/16 NHS STANDARD CONTRACT FOR ACUTE, AMBULANCE, COMMUNITY AND MENTAL HEALTH AND LEARNING DISABILITY SERVICES (MULTILATERAL)-

Surgical Management of Malignant Pleural Mesothelioma: A Clinical Practice Guideline

Targeted Therapy What the Surgeon Needs to Know

Choosing a Clinical Trial for Advanced Mesothelioma

Advances in Treatment of Malignant Pleural Mesothelioma: A Reason for Hope

What If I Have a Spot on My Lung? Do I Have Cancer? Patient Education Guide

Non-Small Cell Lung Cancer Therapies

PATTERNS OF MORTALITY IN ASBESTOS FACTORY WORKERS IN LONDON*

Lung cancer case study

Table of Contents. Data Supplement 1: Summary of ASTRO Guideline Statements. Data Supplement 2: Definition of Terms

Asbestos related cancers

BY THE NUMBERS: THE FUTURE OF MESOTHELIOMA IN AMERICA

CMScript. Member of a medical scheme? Know your guaranteed benefits! Issue 7 of 2014

Recommendations for cross-sectional imaging in cancer management, Second edition

Transcription:

Mesothelioma 1. Introduction 1.1 General Information and Aetiology Mesotheliomas are tumours that arise from the mesothelial cells of the pleura, peritoneum, pericardium or tunica vaginalis [1]. Most are pleural mesotheliomas, the peritoneum is the second most common site of mesothelioma development. Pericardial en tunica vaginalis origin is rare [1]. After a peak, it is estimated that the incidence will decline by the year 2018. Exposure to asbestos is a well-documented etiological factor for mesothelioma, with occupational exposure being reported in 70-80% of those affected [2-4]. Mostly the delay is about 20 years although more than 40 years can elapse between exposure to asbestos and the diagnosis of mesothelioma [2-3]. There is also a good known synergistic effect between nicotine smoking and asbestos [5]. Most mesothelioma occur in males between 50-70 years old and the most frequently reported symptoms are dyspnea, thoracic pain and coughing [5]. 1

Figure 1. Mesothelioma 1.2 Diagnosis and Treatment Most people initially undergo basic chest X-ray because of their complaints [5]. In case an abnormality is detected, a more detailed imaging (CT-scan, PET-scan or MRI) will be performed. If mesothelioma is suspected, a biopsy will be recommended to confirm the diagnosis. Most frequently a thoracoscopy is done to receive a biopsy for a pleural mesothelioma [5]. When there is assumption of a peritoneal mesothelioma, a peritoneoscopy to receive a biopsy may be performed. Biopsies may also be taken during more invasive surgical procedures [5]. Treatment options for mesothelioma include surgery, chemotherapy and radiation therapy. The treatment-choice depends on the general condition of the patient and the stage of the disease. Where possible, it s preferred to combine two or more of these treatments [6]. In clinical trials, this 2

multimodal therapy has been shown to improve survival rates [6]. Although early stage cancers may be operated with curative intent, prognosis of mesothelioma is very poor with almost no long term survivors. Sometimes, tumor cells can grow along the tract where biopsy is taken. To prevent painful lesions along the biopsy tract, this area is preventively treated with radiation therapy. 2. Data Selection All mesotheliomias diagnosed between 2004 and 2007 for patients with an official residence in the Flemish Region are selected, resulting in 623 cases (for detailed information on selected topography and morphology codes, see Appendix A). As described in Figure 2, 67 of them are excluded, resulting in 556 patients for whom results are presented in this chapter. Mesothelioma, incidence 2004-2007 Official residence in the Flemish Region Certain date of diagnosis Patients unique national number available n=623 Subsequent tumours n= 62 n=561 Date of diagnosis = date of death n= 1 n= 560 Patients younger than 15 years n= 0 n=560 No link with data of HIC n= 4 Total number in analyses n= 556 Figure 2. Selection of Mesothelioma (Flemish Region, 2004-2007) 3

3. Patient Characteristics Mesotheliomas in the Flemish Region are more frequent in males than in females (male/female ratio: 6.08) during the incidence years 2004-2007 (Table 1). No clear trend in the age-standardised rates can be observed in the studied period. The median age at diagnosis is almost the same for males and females: 70 years in males and 70.5 years in females. The minimum age is 18 years while the maximum is 90 years. For further analyses, patients are divided into three age groups: 15-59 years, 60-74 years and 75 years or older (Table 2). Table 1. Mesothelioma: Incidence (Flemish Region, 2004-2007) Males Females Total Incidence year n ESR n ESR n ESR 2004 115 3.04 17 0.36 132 1.60 2005 114 3.05 29 0.69 143 1.75 2006 122 3.16 18 0.43 140 1.72 2007 115 2.94 26 0.49 141 1.62 2004-2007 466 3.04 90 0.50 556 1.67 ESR: age-standardised rate, using the European Standard Population (n/100,000 person years) Table 2. Mesothelioma: Age Distribution (Flemish Region, 2004-2007) Males Females Total 15-59 years 83 21 104 60-74 years 255 39 294 75+ years 128 30 158 4. Tumour Characteristics Table 3 presents information regarding the sublocalisation, morphology, differentiation grade and stage (clinical, pathological and combined stage) of the selected mesotheliomas. Only two patients are diagnosed with a non-pleural localised mesothelioma The majority of the tumours have an unknown differentiation grade. However, it should be noted that the relevance of any form of differentiation grading is doubtful for mesothelioma which are not ordinarily graded and for which no prognostic value has yet been attributed to this tumour characteristic [7]. The stage of the 4

tumours remains unknown for about half of the patients. For the patients with a known stage, stages are more or less evenly distributed. Two tumours (0.4%) could not be staged because their localisation was coded as C45.2 (mesothelioma of pericardium) or C45.7 (mesothelioma of other sites). These tumours are displayed as stage NA. Table 3. Mesothelioma: Tumour Characteristics (Flemish Region, 2004-2007) N % of total % of known Localisation Mesothelioma of pleura (C45.0) 554 99.6 99.8 Mesothelioma of pericardium (C45.2) 1 0.2 0.2 Mesothelioma of other sites (C45.7) 1 0.2 / Morphology Epithelioid mesothelioma 219 39.4 / Other morphologies 337 60.6 / Differentiation grade Well differentiated 16 2.9 26.7 Moderately differentiated 11 2.0 18.3 Poorly differentiated 19 3.4 31.7 Undifferentiated 14 2.5 23.3 Unknown 496 89.2 / Clinical stage I 57 10.3 20.9 II 64 11.6 23.4 III 70 12.6 25.6 IV 82 14.8 30.0 Unknown 281 50.7 / Pathological stage I 11 2.0 20.0 II 10 1.8 18.2 III 19 3.4 34.5 IV 15 2.7 27.3 5

Percentage of Patients (%) Unknown 499 90.1 / Combined stage I 59 10.6 20.7 II 63 11.4 22.1 III 76 13.7 26.7 IV 87 15.7 30.5 Unknown 269 48.6 / Note: 2 cases have a localisation for which staging is not applicable (NA) Stage distribution is comparable for males and females, but the proportion of females with an unknown stage is higher (Figure 3). Younger patients tend to have less stage I cancers, although they also have less stage IV cancers in comparison with older patients (Figure 4). The proportion of tumours with an unknown stage is much higher for patients aged 75 years or older than for the other age groups. 100 90 80 70 60 50 40 30 20 10 0 I-IV X I-IV X X IV III II I Males Sex Females Figure 3. Mesothelioma: Stage Distribution by Sex (Flemish Region, 2004-2007) 6

Percentage of Patients (%) 100 90 80 70 60 50 40 30 20 10 0 I-IV X I-IV X I-IV X 15-59 years 60-74 years 75+ years Age Group X IV III II I Figure 4. Mesothelioma: Stage Distribution by Age Group (Flemish Region, 2004-2007) 5. Diagnostic and Therapeutic Procedures 5.1 Diagnosis and Staging An overview of the diagnosis and staging procedures used for mesotheliomas is shown in Table 4. Histological examination is performed in almost all patients (98.6%) and most often a cytological diagnosis is also charged. Only for one patient, no imaging procedure has been charged in the staging procedure. The most frequently used imaging techniques are a CT scan (98.4%) and a X-ray of the thorax (98.7%). MRI scanning is almost never ( 3.2 %) executed during the staging process of mesothelioma. A punction of the pleura (or ascites) is also performed in about two-third of the patients. Surgical staging by mediastinoscopy or explorative thoracotomy is carried out in about one-third of the patients. PET scanning is performed in almost half of the patients (45.0 %). 7

Table 4. Mesothelioma: Overview of Diagnostic and Staging Procedures (Flemish Region, 2004-2007) Diagnostic Procedure Total 2004 2005 2006 2007 (-3m<inc<+3m) (N=556) (N=132) (N=143) (N=140) (N=141) n % n % n % n % n % Tissue Examination 548 98.6 128 97.0 142 99.3 139 99.3 139 98.6 Histological Diagnosis 545 98.0 127 96.2 141 98.6 139 99.3 138 97.9 Cytology 491 88.3 110 83.3 129 90.2 125 89.3 127 90.1 Imaging 555 99.8 132 100.0 142 99.3 140 100.0 141 100.0 CT 547 98.4 128 97.0 141 98.6 140 100.0 138 97.9 MRI 18 3.2 5 3.8 7 4.9 6 4.3 0 0.0 Chest X-ray 549 98.7 128 97.0 141 98.6 139 99.3 141 100.0 PET Scan 250 45.0 62 47.0 61 42.7 71 50.7 56 39.7 CT/MRI Skull 182 32.7 43 32.6 43 30.1 51 36.4 45 31.9 Punction Ascites or Pleural Punction 362 65.1 86 65.2 104 72.7 84 60.0 88 62.4 Surgical Staging 181 32.6 40 30.3 49 34.3 46 32.9 46 32.6 Mediastinoscopy 66 11.9 12 9.1 25 17.5 19 13.6 10 7.1 Explorative Thoracotomy 139 25.0 34 25.8 31 21.7 32 22.9 42 29.8 8

5.2 Multidisciplinary Oncological Consult Overall, about 66% of all mesothelioma patients have been discussed at a multidisciplinary oncological consult (MOC) within one month before till three months after incidence date. No clear trend can be observed over the incidence years (Table 5). Table 5. Mesothelioma: Frequency of Multidisciplinary Oncological Consult (Flemish Region, 2004-2007) MOC Incidence year n % 2004 (n=132) 80 60.6 2005 (n=143) 97 67.8 2006 (n=140) 102 72.9 2007 (n=141) 87 61.7 Total (n=566) 366 65.8 5.3 Therapeutic Procedures Two types of surgery are taken into account: pleural resection and pneumonectomy. The surgery type closest to the incidence date is selected. Based on this criterion, 68.2% of the patients who are operated receive a pleural resection while 31.8% receive a pneumonectomy within the timeframe of one month before until six months after the incidence date (Table 6). Table 6. Mesothelioma: Overview of the Selected Surgeries (Flemish Region, 2004-2007) Type of Surgery n % Pleural Resection 73 68.2 Pneumonectomy 34 31.8 Some patients without major surgical intervention receive a supportive surgical treatment such as pleurodesis (n=200) or a thoracotomy with intent to resection (n=4). Almost 20% of the patients undergo surgery in a time-frame of one month before until six months after incidence. Surgery as the sole therapy is seldom ( 3.1%); the majority of the surgically treated patients receive neo-adjuvant and/or adjuvant chemo- and/or radiotherapy. 9

22.8% of the patients receives concomitant chemoradiotherapy without surgery. Radiotherapy is the only oncological treatment for 15.8% of the patients, while 18.7% of the mesothelioma patients only receive chemotherapy (Table 7). It should be noted that it is unknown whether irradiation (alone or combined with surgery and/or chemotherapy) is performed with a curative intent, a palliative intent or whether it is an irradiation of the entrance gate of the scoop after an endoscopic intervention. No primary oncological treatment is found for 23.4% of the patients. This high percentage of untreated patients can at least partly be explained by the lethal character of this cancer type. Certainly in case of advanced disease in older patients, treatment might be restricted to palliation and comfort care. Table 7. Mesothelioma: Overview of Treatment Schemes (Flemish Region, 2004-2007) Treatment Scheme n % Surgery 107 19.2 No other therapy 17 3.1 Adjuvant radiotherapy 14 2.5 Adjuvant chemoradiotherapy 19 3.4 Adjuvant chemotherapy 27 4.9 Chemotherapy < surgery 2 0.4 Chemotherapy < surgery < chemotherapy 1 0.2 Chemotherapy < surgery < chemoradiotherapy 2 0.4 Chemotherapy < surgery < radiotherapy 10 1.8 Chemoradiotherapy < surgery 4 0.7 Chemoradiotherapy < surgery < radiotherapy 10 1.8 Radiotherapy < surgery < chemoradiotherapy 1 0.2 Radiotherapy 88 15.8 Chemoradiotherapy 127 22.8 Chemotherapy only 104 18.7 No primary treatment registered 130 23.4 10

6. Survival 6.1 Observed and Relative Survival Survival is very poor for all patients diagnosed with a mesothelioma (Table 8). Within one year after diagnosis, more than half of the patients has already died. Relative survival at five years after diagnosis is only 5.0%. Table 8. Mesothelioma: Observed and Relative Survival (Flemish Region, 2004-2007) Observed Survival (%) Relative Survival (%) N at risk 1 year 2 year 3 year 4 year 5 year 1 year 2 year 3 year 4 year 5 year 556 45.9 19.4 9.7 6.1 4.3 47.4 20.6 10.6 6.9 5.0 6.2 Relative Survival by Sex Both males and females have very low 5-year relative survival rates. Survival is somewhat better for females although the absolute differences are small (Table 9). Table 9. Mesothelioma: Relative Survival by Sex (Flemish Region, 2004-2007) Relative Survival (%) N at risk % 1 year 2 year 3 year 4 year 5 year Males 466 83.8 46.6 20.6 9.6 6.5 4.5 Females 90 16.2 51.0 20.8 15.4 8.6 7.7 6.3 Relative Survival by Age Group One year after diagnosis, survival is worse for patients aged 75 year and older, but the survival benefit for the younger patients disappears with a longer follow-up (Table 10). Table 10. Mesothelioma: Relative Survival by Age Group (Flemish Region, 2004-2007) Relative Survival (%) N at risk % 1 year 2 year 3 year 4 year 5 year 15-59 years 104 18.7 54.1 23.3 10.7 5.9 5.9 60-74 years 294 52.9 53.5 23.4 11.6 8.1 4.9 75+ years 158 28.4 30.6 13.2 8.7 5.2 4.8 11

Relative Survival (%) 6.4 Relative Survival by Stage Until three years after diagnosis, survival is remarkably better for the stage I tumours than for the other stages (Figure 5). Thereafter, survival benefit becomes smaller although prognosis remains slightly better. 100 90 80 70 60 50 40 30 20 10 0 0 1 2 3 4 5 Survival Time (years) Stage I Stage II Stage III Stage IV Stage X Figure 5. Mesothelioma: Relative Survival by Stage (Flemish Region, 2004-2007) 6.5 Relative Survival by Morphology Patients diagnosed with an epithelioid mesothelioma (n=219) have a relative survival benefit of 20.3% at 1 year after diagnosis, in comparison with patients diagnosed with another morphological type of mesothelioma (n=337, Figure 6). However, relative survival benefit decreases with increasing follow-up time to only 2.1% at 5 years. 12

Relative Survival (%) Relative Survival (%) 100 90 80 70 60 50 40 30 20 10 0 0 1 2 3 4 5 Survival Time (years) Epithelioid Other Figure 6. Mesothelioma: Relative Survival by Morphology (Flemish Region, 2004-2007) 6.6 Relative Survival by Primary Treatment Patients who undergo surgery (pleural resection or pneumonectomy, n=107) have a slightly better survival than patients who only undergo radio- and/or chemotherapy or without any registered treatment (n=449, Figure 7). The survival benefit seems to shrink after three years of follow-up: at three years the relative survival rates are 14.8% and 9.6% in favour of surgically treated patients, and at five years the rates are 7.2% and 4.5% respectively. 100 90 80 70 60 50 40 30 20 10 0 0 1 2 3 4 5 Survival Time (years) Surgery Other Figure 7. Mesothelioma: Relative Survival by Primary Treatment (Flemish Region, 2004-2007) 13

Number of Patients diagnosed with Mesothelioma 7. Analyses by Volume During the period 2004-2007, Belgian patients with mesothelioma are treated in 49 different Flemish hospitals. The mean number of patients (during the period 2004-2007) by hospital is 9.9 and the median number is 4, with a range between 1 and 69. The distribution of the number of patients (=volume) per hospital is displayed in Figure 8. 70 60 50 40 30 20 10 0 Hospital Figure 8. Mesothelioma: Distribution of Patients by Hospital (Flemish Hospitals, 2004-2007) 477 of the Flemish patients (85.8%) can be assigned to a hospital (see Methodology for the rules applied to assign a patient to one hospital). Considering hospitals having taken care of 40 or more patients diagnosed during the period 2004-2007 as high-volume hospitals, 150 patients are assigned to high-volume hospitals and 327 are assigned to low-volume hospitals. Treatment schemes are different for those considered high-and low-volume hospitals (Figure 9). In high-volume hospitals, 34.0% of the patients is primarily treated with RT and 34.7% with chemoradiotherapy. Surgery (with or without neo- and/or adjuvant treatment) and chemotherapy only, are less frequently used. For low-volume hospitals a larger part of the patients is surgically treated (26.6%). Chemotherapy only and chemoradiotherapy are both used in about one fourth of 14

Percentage of Patients by Treatment the patients (24.8% and 22.9% respectively). Additionally, the number of patients without any oncological treatment is higher in low-volume hospitals (15.0%) than high-volume hospitals (3.3%). It should be noted that the difference in the proportion of patients treated with radio- or chemoradiotherapy in the high-volume versus low-volume hospitals can at least partly be explained by the rules for assignment that give a rather high priority to the hospital were the RT takes place. 100 90 80 70 60 50 40 30 20 10 0 High-Volume Hospital Volume Low-Volume NONE CHEMO/RT CHEMO SURG RT Figure 9. Mesothelioma: Primary Treatment by Hospital Volume (High-Volume versus Low-Volume Hospitals) (Flemish Region, 2004-2007) 8. References 1. Mesothelioma risks and causes : Cancer Research UK : CancerHelp UK. http://www.cancerresearchuk.org/cancer-help/type/mesothelioma/. Accessed on October 1, 2013. 2. Roggli VL, Sharma A, Butnor KJ et al. Malignant mesothelioma and occupational exposure to asbestos: a clinicopathological correlation of 1445 cases. Ultrastruct Pathol 2000; 26: 2: 55 65. 3. Gennaro V, Finkelstein MM, Ceppi M, et al. Mesothelioma and lung tumors attributable to asbestos among petroleum workers. Am. J. Ind. Med. 2000; 37: 275 282. 4. Muscat JE, Wynder EL. Cigarette smoking, asbestos exposure, and malignant mesothelioma. Cancer Res 1991; 51: 2263 2267. 5. Barreiro, TJ; Katzman, PJ. Malignant mesothelioma: a case presentation and review. The Journal of the American Osteopathic Association 2006; 106: 699 704. 15

6. Sugarbaker DJ, Flores RM, Jaklitsch MT et al. Resection margins, extrapleural nodal status, and cell type determine postoperative long-term survival in trimodality therapy of malignant pleural mesothelioma: results in 183 patients. J Thorac Cardiovasc Surg 1999; 117: 54 63. 7. Travis WD, Brambilla E, Müller-Hermelinck HK et al (eds). World Health Organization Classification of Tumours. Pathology & Genetics. Tumours of the Lung, Pleura, Thymus and Heart. Lyon, IARC Press, 2004. 16