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==Overview==
==Overview==
Mesothelioma is a rare, highly aggressive cancer which arises from the [[mesothelial cells]] which form the lining of the [[pleural]], and less frequently the [[peritoneal]], [[pericardial]], and [[tunica vaginalis]] cavities. Mesothelioma is a form of cancer that is most commonly caused by exposure to [[asbestos]]. Wagner et al. were the first to discover the association between [[asbestos|asbestos exposure]] and development of mesothelioma. Mesothelioma may be classified into several subtypes based on the location (pleural, peritoneal, pericardial, cystic/multicystic, and tunica vaginalis testis), histology (epithelial, sarcomatoid, and biphasic), and potential to spread (benign and malignant). [[Asbestos]] causes DNA damage directly by mechanically interfering with the segregation of [[chromosomes]] during [[mitosis]] and indirectly by inducing [[mesothelial cells]] and [[macrophages]], to release mutagenic [[reactive oxygen]] and nitrogen species. Asbestos fibres have been shown to alter the function and secretory properties of [[macrophages]], ultimately creating conditions which favor the development of mesothelioma. Following asbestos [[phagocytosis]], macrophages generate increased amounts of hydroxyl radicals, which are normal by-products of cellular anaerobic metabolism. However, these free radicals are also known clastogenic and membrane-active agents thought to promote asbestos carcinogenicity. These oxidants can participate in the oncogenic process by directly and indirectly interacting with DNA, modifying membrane-associated cellular events, including oncogene activation and perturbation of cellular antioxidant defences. Genes involved in the pathogenesis of mesothelioma include ''[[BAP1]]'', ''[[CDKN2A]]'', ''[[WT1]]'', ''[[NF2 gene|NF2]]'', and ''[[TP53]]''. On gross pathology, pleural mesothelioma is characterized by discrete plaques and nodules that coalesce to produce a sheet-like tumor, with the pleural surface seeding of malignant mesothelioma cells. Based on the histology, mesothelioma may be classified into 3 subtypes: epithelial, sarcomatoid, and biphagic. Mesothelioma is demonstrated by positivity to [[tumor marker]]s, such as [[calretinin]], epithelial membrane antigen, [[cytokeratin]], and [[mesothelin]]. Mesothelioma must be differentiated from [[pleural effusion]], [[lung cancer]], [[pulmonary tuberculosis]], [[tuberculosis|peritoneal tuberculosis]], [[pseudomyxoma peritonei]], [[constrictive pericarditis]], [[cystadenoma|ovarian cystadenoma]], and mesothelial hyperplasia of the testis. If left untreated, mesothelioma may progress to develop [[dyspnea]], [[dysphagia]], [[pleural effusion]], [[thrombophlebitis]], [[constrictive pericarditis]], [[hydrocele|recurrent hydrocele]], and [[metastases]], depending on the site involved. Complications of mesothelioma include [[pleural effusion]], [[spinal cord compression]], [[Horner's syndrome]], [[superior vena cava syndrome]], hyperviscocity syndrome, [[pericardial effusion]], [[cardiac tamponade]], [[heart failure]], [[ascites]], and [[hydrocele|recurrent hydrocele]]. The prognosis of mesothelioma depends on the cell subtype. According to the Union for International Cancer Control staging system, there are four stages of pleural mesothelioma based on the primary tumor, lymph nodes, and metastasis: stage I (IA, IB), stage II, stage III, and stage IV.<ref name="Stagesofpleuralmesothelioma1">Stages of pleural mesothelioma. Canadian cancer society 2016. http://www.cancer.ca/en/cancer-information/cancer-type/mesothelioma/staging/?region=on. Accessed on February 6, 2016</ref> There is no established staging system for peritoneal mesothelioma. When evaluating a patient for mesothelioma, you should take a detailed history of the presenting symptom (onset, duration, and progression), other associated symptoms, and a thorough family and past medical history review. Other specific areas of focus include a history of any exposure to [[asbestos]] or [[radiation]]. Symptoms of mesothelioma may not appear until 20 to 50 years after exposure to [[asbestos]]. Symptoms of mesothelioma include [[chest pain]], [[shortness of breath]], [[cough]], [[abdominal pain]], [[palpitation]], [[hemoptysis]], and [[pedal edema|swelling in the legs]].  CT is the most commonly used modality for the assessment of mesothelioma and is able to stage the disease accurately in majority of the patients. [[Chemotherapy]] is one of the mainstay of therapy for mesothelioma. Other therapies for mesothelioma include [[radiotherapy]], [[surgery]], and supportive care. Effective measures for the primary prevention of mesothelioma include removal of asbestos from schools and other public buildings. Secondary prevention strategies following mesothelioma include regular checkups, [[CXR|chest x-rays]], and/or [[CT|CT scans]] in high-risk individuals.  
Mesothelioma is a rare, highly aggressive cancer which arises from the [[mesothelial cells]] which form the lining of the [[pleural]], and less frequently the [[peritoneal]], [[pericardial]], and [[tunica vaginalis]] cavities. Mesothelioma is a form of cancer that is most commonly caused by exposure to [[asbestos]]. Wagner et al. were the first to discover the association between [[asbestos|asbestos exposure]] and development of mesothelioma. Mesothelioma may be classified into several subtypes based on the location (pleural, peritoneal, pericardial, cystic/multicystic, and tunica vaginalis testis), histology (epithelial, sarcomatoid, and biphasic), and potential to spread (benign and malignant). [[Asbestos]] causes DNA damage directly by mechanically interfering with the segregation of [[chromosomes]] during [[mitosis]] and indirectly by inducing [[mesothelial cells]] and [[macrophages]], to release mutagenic [[reactive oxygen]] and nitrogen species. Asbestos fibres have been shown to alter the function and secretory properties of [[macrophages]], ultimately creating conditions which favor the development of mesothelioma. Following asbestos [[phagocytosis]], macrophages generate increased amounts of hydroxyl radicals, which are normal by-products of cellular anaerobic metabolism. However, these free radicals are also known clastogenic and membrane-active agents thought to promote asbestos carcinogenicity. These oxidants can participate in the oncogenic process by directly and indirectly interacting with DNA, modifying membrane-associated cellular events, including oncogene activation and perturbation of cellular antioxidant defences. Genes involved in the pathogenesis of mesothelioma include ''[[BAP1]]'', ''[[CDKN2A]]'', ''[[WT1]]'', ''[[NF2 gene|NF2]]'', and ''[[TP53]]''. On gross pathology, pleural mesothelioma is characterized by discrete plaques and nodules that coalesce to produce a sheet-like tumor, with the pleural surface seeding of malignant mesothelioma cells. Based on the histology, mesothelioma may be classified into 3 subtypes: epithelial, sarcomatoid, and biphagic. Mesothelioma is demonstrated by positivity to [[tumor marker]]s, such as [[calretinin]], epithelial membrane antigen, [[cytokeratin]], and [[mesothelin]]. Mesothelioma must be differentiated from [[pleural effusion]], [[lung cancer]], [[pulmonary tuberculosis]], [[tuberculosis|peritoneal tuberculosis]], [[pseudomyxoma peritonei]], [[constrictive pericarditis]], [[cystadenoma|ovarian cystadenoma]], and mesothelial hyperplasia of the testis. If left untreated, mesothelioma may progress to develop [[dyspnea]], [[dysphagia]], [[pleural effusion]], [[thrombophlebitis]], [[constrictive pericarditis]], [[hydrocele|recurrent hydrocele]], and [[metastases]], depending on the site involved. Complications of mesothelioma include [[pleural effusion]], [[spinal cord compression]], [[Horner's syndrome]], [[superior vena cava syndrome]], hyperviscocity syndrome, [[pericardial effusion]], [[cardiac tamponade]], [[heart failure]], [[ascites]], and [[hydrocele|recurrent hydrocele]]. The prognosis of mesothelioma depends on the cell subtype. According to the Union for International Cancer Control staging system, there are four stages of pleural mesothelioma based on the primary tumor, lymph nodes, and metastasis: stage I (IA, IB), stage II, stage III, and stage IV. There is no established staging system for peritoneal mesothelioma. When evaluating a patient for mesothelioma, you should take a detailed history of the presenting symptom (onset, duration, and progression), other associated symptoms, and a thorough family and past medical history review. Other specific areas of focus include a history of any exposure to [[asbestos]] or [[radiation]]. Symptoms of mesothelioma may not appear until 20 to 50 years after exposure to [[asbestos]]. Symptoms of mesothelioma include [[chest pain]], [[shortness of breath]], [[cough]], [[abdominal pain]], [[palpitation]], [[hemoptysis]], and [[pedal edema|swelling in the legs]].  CT is the most commonly used modality for the assessment of mesothelioma and is able to stage the disease accurately in majority of the patients. [[Chemotherapy]] is one of the mainstay of therapy for mesothelioma. Other therapies for mesothelioma include [[radiotherapy]], [[surgery]], and supportive care. Effective measures for the primary prevention of mesothelioma include removal of asbestos from schools and other public buildings. Secondary prevention strategies following mesothelioma include regular checkups, [[CXR|chest x-rays]], and/or [[CT|CT scans]] in high-risk individuals.  


==Historical Perspective==
==Historical Perspective==

Latest revision as of 16:34, 25 April 2018

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Overview

Historical Perspective

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Causes

Differentiating Mesothelioma from other Diseases

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Risk Factors

Screening

Natural History, Complications and Prognosis

Diagnosis

Staging

History and Symptoms

Physical Examination

Laboratory Findings

Chest X Ray

CT

MRI

Ultrasound

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Other Imaging Findings

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Summary of Treatment for Pleural Mesothelioma

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Sujit Routray, M.D. [2]

Overview

Mesothelioma is a rare, highly aggressive cancer which arises from the mesothelial cells which form the lining of the pleural, and less frequently the peritoneal, pericardial, and tunica vaginalis cavities. Mesothelioma is a form of cancer that is most commonly caused by exposure to asbestos. Wagner et al. were the first to discover the association between asbestos exposure and development of mesothelioma. Mesothelioma may be classified into several subtypes based on the location (pleural, peritoneal, pericardial, cystic/multicystic, and tunica vaginalis testis), histology (epithelial, sarcomatoid, and biphasic), and potential to spread (benign and malignant). Asbestos causes DNA damage directly by mechanically interfering with the segregation of chromosomes during mitosis and indirectly by inducing mesothelial cells and macrophages, to release mutagenic reactive oxygen and nitrogen species. Asbestos fibres have been shown to alter the function and secretory properties of macrophages, ultimately creating conditions which favor the development of mesothelioma. Following asbestos phagocytosis, macrophages generate increased amounts of hydroxyl radicals, which are normal by-products of cellular anaerobic metabolism. However, these free radicals are also known clastogenic and membrane-active agents thought to promote asbestos carcinogenicity. These oxidants can participate in the oncogenic process by directly and indirectly interacting with DNA, modifying membrane-associated cellular events, including oncogene activation and perturbation of cellular antioxidant defences. Genes involved in the pathogenesis of mesothelioma include BAP1, CDKN2A, WT1, NF2, and TP53. On gross pathology, pleural mesothelioma is characterized by discrete plaques and nodules that coalesce to produce a sheet-like tumor, with the pleural surface seeding of malignant mesothelioma cells. Based on the histology, mesothelioma may be classified into 3 subtypes: epithelial, sarcomatoid, and biphagic. Mesothelioma is demonstrated by positivity to tumor markers, such as calretinin, epithelial membrane antigen, cytokeratin, and mesothelin. Mesothelioma must be differentiated from pleural effusion, lung cancer, pulmonary tuberculosis, peritoneal tuberculosis, pseudomyxoma peritonei, constrictive pericarditis, ovarian cystadenoma, and mesothelial hyperplasia of the testis. If left untreated, mesothelioma may progress to develop dyspnea, dysphagia, pleural effusion, thrombophlebitis, constrictive pericarditis, recurrent hydrocele, and metastases, depending on the site involved. Complications of mesothelioma include pleural effusion, spinal cord compression, Horner's syndrome, superior vena cava syndrome, hyperviscocity syndrome, pericardial effusion, cardiac tamponade, heart failure, ascites, and recurrent hydrocele. The prognosis of mesothelioma depends on the cell subtype. According to the Union for International Cancer Control staging system, there are four stages of pleural mesothelioma based on the primary tumor, lymph nodes, and metastasis: stage I (IA, IB), stage II, stage III, and stage IV. There is no established staging system for peritoneal mesothelioma. When evaluating a patient for mesothelioma, you should take a detailed history of the presenting symptom (onset, duration, and progression), other associated symptoms, and a thorough family and past medical history review. Other specific areas of focus include a history of any exposure to asbestos or radiation. Symptoms of mesothelioma may not appear until 20 to 50 years after exposure to asbestos. Symptoms of mesothelioma include chest pain, shortness of breath, cough, abdominal pain, palpitation, hemoptysis, and swelling in the legs. CT is the most commonly used modality for the assessment of mesothelioma and is able to stage the disease accurately in majority of the patients. Chemotherapy is one of the mainstay of therapy for mesothelioma. Other therapies for mesothelioma include radiotherapy, surgery, and supportive care. Effective measures for the primary prevention of mesothelioma include removal of asbestos from schools and other public buildings. Secondary prevention strategies following mesothelioma include regular checkups, chest x-rays, and/or CT scans in high-risk individuals.

Historical Perspective

Wagner et al. were the first to discover the association between asbestos exposure and development of mesothelioma.

Classification

Mesothelioma may be classified into several subtypes based on the location (pleural, peritoneal, pericardial, cystic/multicystic, and tunica vaginalis testis), histology (epithelial, sarcomatoid, and biphasic), and potential to spread (benign and malignant).

Pathophysiology

Asbestos causes DNA damage directly by mechanically interfering with the segregation of chromosomes during mitosis and indirectly by inducing mesothelial cells and macrophages, to release mutagenic reactive oxygen and nitrogen species. Asbestos fibres have been shown to alter the function and secretory properties of macrophages, ultimately creating conditions which favor the development of mesothelioma. Following asbestos phagocytosis, macrophages generate increased amounts of hydroxyl radicals, which are normal by-products of cellular anaerobic metabolism. However, these free radicals are also known clastogenic and membrane-active agents thought to promote asbestos carcinogenicity. These oxidants can participate in the oncogenic process by directly and indirectly interacting with DNA, modifying membrane-associated cellular events, including oncogene activation and perturbation of cellular antioxidant defences. Genes involved in the pathogenesis of mesothelioma include BAP1, CDKN2A, WT1, NF2, and TP53. On gross pathology, pleural mesothelioma is characterized by discrete plaques and nodules that coalesce to produce a sheet-like tumor, with the pleural surface seeding of malignant mesothelioma cells. Based on the histology, mesothelioma may be classified into 3 subtypes: epithelial, sarcomatoid, and biphagic. Mesothelioma is demonstrated by positivity to tumor markers, such as calretinin, epithelial membrane antigen, cytokeratin, and mesothelin.

Causes

Common causes of mesothelioma include asbestos-fibre exposure, erionite-fibre exposure, Simian virus 40, and radiation exposure.

Differentiating Mesothelioma from other Diseases

Mesothelioma must be differentiated from pleural effusion, lung cancer, pulmonary tuberculosis, peritoneal tuberculosis, pseudomyxoma peritonei, constrictive pericarditis, ovarian cystadenoma, and mesothelial hyperplasia of the testis.

Epidemiology and Demographics

Mesothelioma is a rare disease which accounts for 5-28% of all malignancies that involve the pleura. The incidence of mesothelioma is estimated to be 3,000 cases annually. The incidence of pleural mesothelioma is approximately 1 per 100,000 individuals in the United States. Males are more commonly affected with mesothelioma than females. The male to female ratio is approximately 3 to 1. The incidence of mesothelioma increases with age; the median age at diagnosis for pleural mesothelioma and peritoneal mesothelioma are 74 years and 68 years, respectively. There is no racial predilection to mesothelioma.

Risk Factors

The most potent risk factor in the development of mesothelioma is asbestos exopsure. Other risk factors include erionite-fibre exposure, Simian virus 40, and radiation exposure.

Screening

There is insufficient evidence to recommend routine screening for mesothelioma.

Natural History, Complications and Prognosis

If left untreated, mesothelioma may progress to develop dyspnea, dysphagia, pleural effusion, thrombophlebitis, constrictive pericarditis, recurrent hydrocele, and metastases, depending on the site involved. Complications of mesothelioma include pleural effusion, spinal cord compression, Horner's syndrome, superior vena cava syndrome, hyperviscocity syndrome, pericardial effusion, cardiac tamponade, heart failure, ascites, and recurrent hydrocele. The prognosis of mesothelioma depends on the cell subtype.

Diagnosis

Staging

According to the Union for International Cancer Control staging system, there are four stages of pleural mesothelioma based on the primary tumor, lymph nodes, and metastasis: stage I (IA, IB), stage II, stage III, and stage IV. There is no established staging system for peritoneal mesothelioma.

History and Symptoms

When evaluating a patient for mesothelioma, you should take a detailed history of the presenting symptom (onset, duration, and progression), other associated symptoms, and a thorough family and past medical history review. Other specific areas of focus include a history of any exposure to asbestos or radiation. Symptoms of mesothelioma may not appear until 20 to 50 years after exposure to asbestos. Symptoms of mesothelioma include chest pain, shortness of breath, cough, abdominal pain, palpitation, hemoptysis, and swelling in the legs.

Physical Examination

Common physical examination findings of mesothelioma include dullness on percussion and decreased breath sounds on ausculatation of the lung, ascites, abdominal mass, hemoptysis, pedal edema, and murmurs.

Laboratory Findings

Laboratory findings consistent with the diagnosis of mesothelioma include abnormal pleural fluid analysis (decreased pleural pH and pleural fluid/serum glucose ratio).

Chest X Ray

Chest x-rays are of limited utility and are non-specific in a case of mesothelioma, demonstrating a pleural opacity which may extend around and encase the lung.

CT

Chest CT scan may be diagnostic of mesothelioma. CT is the most commonly used modality for the assessment of mesothelioma and is able to stage the disease accurately in majority of the patients.

MRI

MRI, although not routinely used, may have a role in refining the staging and better delineating the extent of the disease in surgical candidates especially with regard to chest wall and diaphragmatic invasion. Findings on MRI include iso- to slightly hyperintense on T1-weighted images and iso- to hyperintense on T2-weighted images. There is enhancement on contrast administration.

Other Diagnostic Studies

Other diagnostic studies for mesothelioma include laparoscopy, thoracoscopy, pleuroscopy, biopsy, position emission tomography scan, and fluorescence in situ hybridization.

Treatment

Medical Therapy

Chemotherapy is one of the mainstay of therapy for mesothelioma. Other therapies for mesothelioma include radiotherapy, surgery, and supportive care.

Surgery

The feasibility of surgery depends on the stage of mesothelioma at diagnosis.

Summary of Treatment for Pleural Mesothelioma

The treatment options vary for the different stages, subtypes, and resectability of pleural mesothelioma. The types of treatment given are also based on the unique needs of the individual with cancer.

Summary of Treatment for Peritoneal Mesothelioma

The types of treatment given are based on the unique needs of the individual with cancer. Peritoneal mesothelioma is a locally aggressive disease that is difficult to treat. The goal of the treatment is to control the disease for as long as possible, manage symptoms, and improve the person’s quality of life.

Primary Prevention

Effective measures for the primary prevention of mesothelioma include removal of asbestos from schools and other public buildings.

Secondary Prevention

Secondary prevention strategies following mesothelioma include regular checkups, chest x-rays, and/or CT scans in high-risk individuals.

References


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