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Revision as of 02:40, 27 November 2017

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Mesothelioma Microchapters

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Patient Information

Overview

Historical Perspective

Classification

Pathophysiology

Causes

Differentiating Mesothelioma from other Diseases

Epidemiology and Demographics

Risk Factors

Screening

Natural History, Complications and Prognosis

Diagnosis

Staging

History and Symptoms

Physical Examination

Laboratory Findings

Chest X Ray

CT

MRI

Ultrasound

Other Diagnostic Studies

Other Imaging Findings

Treatment

Medical Therapy

Surgery

Summary of Treatment for Pleural Mesothelioma

Summary of Treatment for Peritoneal Mesothelioma

Primary Prevention

Secondary Prevention

Cost-Effectiveness of Therapy

Future or Investigational Therapies

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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.[1][2] Mesothelioma is a form of cancer that is most commonly caused by exposure to asbestos.[3]

Historical Perspective

Wagner et al. were the first to discover the association between asbestos exposure and development of mesothelioma.[4]

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).[5][6]

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.[4] 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.[4][7][8][9][10][11][12] 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.[13] Based on the histology, mesothelioma may be classified into 3 subtypes: epithelial, sarcomatoid, and biphagic.[5] Mesothelioma is demonstrated by positivity to tumor markers, such as calretinin, epithelial membrane antigen, cytokeratin, and mesothelin.[14][15]

Causes

Common causes of mesothelioma include asbestos-fibre exposure, erionite-fibre exposure, Simian virus 40, and radiation exposure.[16]

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.[17][18][19][20][21][22][23]

Epidemiology and Demographics

Mesothelioma is a rare disease which accounts for 5-28% of all malignancies that involve the pleura.[13] The incidence of mesothelioma is estimated to be 3,000 cases annually.[1] The incidence of pleural mesothelioma is approximately 1 per 100,000 individuals in the United States.[24] Males are more commonly affected with mesothelioma than females. The male to female ratio is approximately 3 to 1.[13] 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.[4] There is no racial predilection to mesothelioma.[13]

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.[25]

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.[26][27][28][29][30][31][32] 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.[27][28][29][30][31][33][32] The prognosis of mesothelioma depends on the cell subtype.[26]

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.[34] 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.[16] 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.[35]

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.[35]

Laboratory Findings

Laboratory findings consistent with the diagnosis of mesothelioma include abnormal pleural fluid analysis (decreased pleural pH and pleural fluid/serum glucose ratio).[36]

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.[37]

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.[38]

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.[38]

Other Diagnostic Studies

Other diagnostic studies for mesothelioma include laparoscopy, thoracoscopy, pleuroscopy, biopsy, position emission tomography scan, and fluorescence in situ hybridization.[39][40][38][41]

Treatment

Medical Therapy

Chemotherapy is one of the mainstay of therapy for mesothelioma.[42] Other therapies for mesothelioma include radiotherapy, surgery, and supportive care.[43]

Surgery

The feasibility of surgery depends on the stage of mesothelioma at diagnosis.[44]

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.[45]

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.[46]

Primary Prevention

Effective measures for the primary prevention of mesothelioma include removal of asbestos from schools and other public buildings.[47][48]

Secondary Prevention

Secondary prevention strategies following mesothelioma include regular checkups, chest x-rays, and/or CT scans in high-risk individuals.[49]

References

  1. ↑ 1.0 1.1 Philip A. Rascoe, Xiaobo X. Cao and W. Roy Smythe (2012). Molecular Pathogenesis of Malignant Pleural Mesothelioma, Mesotheliomas - Synonyms and Definition, Epidemiology, Etiology, Pathogenesis, Cyto-Histopathological Features, Clinic, Diagnosis, Treatment, Prognosis, Dr Alexander Zubritsky (Ed.), ISBN: 978-953-307-845-8, InTech, Available from: http://www.intechopen.com/books/mesotheliomas-synonyms-and-definition-epidemiology-etiology-pathogenesis-cyto-histopathological-features-clinic-diagnosis-treatment-prognosis/molecular-pathogenesis-of-malignant-pleural-mesothelioma
  2. ↑ Mesothelioma. Wikipedia 2016. https://en.wikipedia.org/wiki/Mesothelioma. Accessed on February 3, 2016
  3. ↑ "Mesothelioma risks and causes : Cancer Research UK : CancerHelp UK". Cancerhelp.org.uk. 2010-06-23. Retrieved 2010-08-20.
  4. ↑ 4.0 4.1 4.2 4.3 Thomas, Anish; Chen, Yuanbin; Yu, Tinghui; Gill, Ammara; Prasad, Vinay (2015). "Distinctive clinical characteristics of malignant mesothelioma in young patients". Oncotarget. 6 (18): 16766–16773. doi:10.18632/oncotarget.4414. ISSN 1949-2553.
  5. ↑ 5.0 5.1 Mesothelioma. Dr Bruno Di Muzio and A.Prof Frank Gaillard et al. Radiopaedia 2016. http://radiopaedia.org/articles/mesothelioma. Accessed on February 8, 2016
  6. ↑ What is mesothelioma. Canadian cancer society 2016. http://www.cancer.ca/en/cancer-information/cancer-type/mesothelioma/mesothelioma/?region=on. Accessed on February 8, 2016
  7. ↑ Ladanyi M (2005). "Implications of P16/CDKN2A deletion in pleural mesotheliomas". Lung Cancer. 49 Suppl 1: S95–8. doi:10.1016/j.lungcan.2005.03.017. PMID 15950811.
  8. ↑ Kumar-Singh S, Segers K, Rodeck U, Backhovens H, Bogers J, Weyler J; et al. (1997). "WT1 mutation in malignant mesothelioma and WT1 immunoreactivity in relation to p53 and growth factor receptor expression, cell-type transition, and prognosis". J Pathol. 181 (1): 67–74. doi:10.1002/(SICI)1096-9896(199701)181:1<67::AID-PATH723>3.0.CO;2-Z. PMID 9072005.
  9. ↑ Ladanyi M, Zauderer MG, Krug LM, Ito T, McMillan R, Bott M; et al. (2012). "New strategies in pleural mesothelioma: BAP1 and NF2 as novel targets for therapeutic development and risk assessment". Clin Cancer Res. 18 (17): 4485–90. doi:10.1158/1078-0432.CCR-11-2375. PMC 3432735. PMID 22825583.
  10. ↑ Andujar P, Pairon JC, Renier A, Descatha A, Hysi I, Abd-Alsamad I; et al. (2013). "Differential mutation profiles and similar intronic TP53 polymorphisms in asbestos-related lung cancer and pleural mesothelioma". Mutagenesis. 28 (3): 323–31. doi:10.1093/mutage/get008. PMID 23435014.
  11. ↑ Opitz I, Soltermann A, Abaecherli M, Hinterberger M, Probst-Hensch N, Stahel R; et al. (2008). "PTEN expression is a strong predictor of survival in mesothelioma patients". Eur J Cardiothorac Surg. 33 (3): 502–6. doi:10.1016/j.ejcts.2007.09.045. PMID 18248818.
  12. ↑ Murakami H, Mizuno T, Taniguchi T, Fujii M, Ishiguro F, Fukui T; et al. (2011). "LATS2 is a tumor suppressor gene of malignant mesothelioma". Cancer Res. 71 (3): 873–83. doi:10.1158/0008-5472.CAN-10-2164. PMID 21245096.
  13. ↑ 13.0 13.1 13.2 13.3 Mesothelioma. CGMH.ORG 2016. https://www1.cgmh.org.tw/intr/intr5/c6700/OBGYN/f/web/Mesothelioma/index.htm. Accessed on February 15, 2016
  14. ↑ Pathology of mesothelioma. Dr Bruno Di Muzio and A.Prof Frank Gaillard et al. Radiopaedia 2016. http://radiopaedia.org/articles/mesothelioma. Accessed on February 10, 2016
  15. ↑ Immunohistochemistry of mesothelioma. Wikipedia 2016. https://en.wikipedia.org/wiki/Mesothelioma. Accessed on February 12, 2016
  16. ↑ 16.0 16.1 Risk factors for mesothelioma. Canadian cancer society 2016. http://www.cancer.ca/en/cancer-information/cancer-type/mesothelioma/risks/?region=on. Accessed on February 8, 2016
  17. ↑ Differential diagnosis of mesothelioma. Dr Bruno Di Muzio and A.Prof Frank Gaillard et al. Radiopaedia 2016. http://radiopaedia.org/articles/mesothelioma. Accessed on February 12, 2016
  18. ↑ Dr Yuranga Weerakkody et al. Radiopaedia 2016. http://radiopaedia.org/articles/pleural-tumours. Accessed on February 12, 2016
  19. ↑ Differential diagnosis of peritoneal mesothelioma. Dr Alexandra Stanislavsky et al. Radiopaedia 2016. http://radiopaedia.org/articles/peritoneal-mesothelioma. Accessed on February 12, 2016
  20. ↑ Primary peritoneal neoplasms. Dr Praveen Jha and Radswiki et al. Radiopaedia 2016. http://radiopaedia.org/articles/primary-peritoneal-neoplasms. Accessed on February 12, 2016
  21. ↑ Seek a Second Opinion to Avoid Misdiagnosis of Pericardial Mesothelioma. Asbestos.com 2016. http://www.asbestos.com/mesothelioma/pericardial.php. Accessed on February 12, 2016
  22. ↑ Differential diagnosis of multicystic mesothelioma. Dr Aditya Shetty and Dr Yuranga Weerakkody et al. Raiopaedia 2016. http://radiopaedia.org/articles/multicystic-mesothelioma. Accessed on February 12, 2016
  23. ↑ Chekol, Seble S; Sun, Chen-Chin (2012). "Malignant Mesothelioma of the Tunica Vaginalis Testis: Diagnostic Studies and Differential Diagnosis". Archives of Pathology & Laboratory Medicine. 136 (1): 113–117. doi:10.5858/arpa.2010-0550-RS. ISSN 0003-9985.
  24. ↑ Saint-Pierre, Mathieu D.; Pease, Christopher; Mithoowani, Hamid; Zhang, Tinghua; Nicholas, Garth A.; Laurie, Scott A.; Wheatley-Price, Paul (2015). "Malignant Pleural Mesothelioma Outcomes in the Era of Combined Platinum and Folate Antimetabolite Chemotherapy". Lung Cancer International. 2015: 1–7. doi:10.1155/2015/590148. ISSN 2090-3197.
  25. ↑ Mesothelioma. Dr Bruno Di Muzio and A.Prof Frank Gaillard et al.Radiopaedia 2016. http://radiopaedia.org/articles/mesothelioma. Accessed on 13th January, 2016
  26. ↑ 26.0 26.1 Survival statistics for mesothelioma. Canadian cancer society 2016. http://www.cancer.ca/en/cancer-information/cancer-type/mesothelioma/prognosis-and-survival/survival-statistics/?region=on. Accessed on February 10, 2016
  27. ↑ 27.0 27.1 Complications of mesothelioma. Mayo clinic 2016. http://www.mayoclinic.org/diseases-conditions/mesothelioma/basics/complications/con-20026157. Accessed on February 13, 2016
  28. ↑ 28.0 28.1 Mensi C, Termine L, Garberi A, Meroni S, Levi D, Balzarini L; et al. (2012). "Spinal cord compression: an unusual presentation of malignant pleural mesothelioma. A case report and review of the literature". Tumori. 98 (4): e92–7. doi:10.1700/1146.12651. PMID 23052177.
  29. ↑ 29.0 29.1 Minami T, Matsumoto K, Aizawa H, Nakano H, Sugio K, Nakashima Y; et al. (1999). "[Horner's syndrome in a patient with diffuse malignant pleural mesothelioma]". Nihon Kokyuki Gakkai Zasshi. 37 (4): 287–90. PMID 10390966.
  30. ↑ 30.0 30.1 Ragalie GF, Varkey B, Choi H (1983). "Malignant pleural mesothelioma presenting as superior vena cava syndrome". Can Med Assoc J. 128 (6): 689–91, 740. PMC 1875200. PMID 6825037.
  31. ↑ 31.0 31.1 Clinical presentation of peritoneal mesothelioma. Dr Alexandra Stanislavsky et al. Radiopaedia 2016. http://radiopaedia.org/articles/peritoneal-mesothelioma. Accessed on February 13, 2016
  32. ↑ 32.0 32.1 Clinical presentation of tunica vaginalis testis mesothelioma. Dr Matt A. Morgan and Dr Dalia Ibrahim et al. Radiopaedia 2016. http://radiopaedia.org/articles/tunica-vaginalis-testis-mesothelioma. Accessed on February 13, 2016
  33. ↑ Complications of pericardial mesothelioma. Dr Henry Knipe and Dr Yuranga Weerakkody et al. Radiopaedia 2016. http://radiopaedia.org/articles/pericardial-mesothelioma. Accessed on February 13, 2016
  34. ↑ 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
  35. ↑ 35.0 35.1 Signs and symptoms of mesothelioma. Wikipedia 2016. https://en.wikipedia.org/wiki/Mesothelioma. Accessed on February 16, 2016
  36. ↑ Gottehrer A, Taryle DA, Reed CE, Sahn SA (1991). "Pleural fluid analysis in malignant mesothelioma. Prognostic implications". Chest. 100 (4): 1003–6. PMID 1914546.
  37. ↑ Mesothelioma. Dr Bruno Di Muzio and A.Prof Frank Gaillard et al. Radiopaedia 2016. http://radiopaedia.org/articles/mesothelioma. Accessed on 13th January, 2016
  38. ↑ 38.0 38.1 38.2 Radiographic findings of mesothelioma. Dr Bruno Di Muzio and A.Prof Frank Gaillard et al. Radiopaedia 2016. http://radiopaedia.org/articles/mesothelioma. Accessed on February 8, 2015
  39. ↑ Alvarez JM, Hasani A, Segal A, Sterret G, Millward M, Nowak A; et al. (2009). "Bilateral thoracoscopy, mediastinoscopy and laparoscopy, in addition to CT, MRI and PET imaging, are essential to correctly stage and treat patients with mesothelioma prior to trimodality therapy". ANZ J Surg. 79 (10): 734–8. doi:10.1111/j.1445-2197.2009.05060.x. PMID 19878170.
  40. ↑ Tests that examine the inside of the chest and abdomen are used to detect (find) and diagnose malignant mesothelioma. National cancer institute 2016. http://www.cancer.gov/types/mesothelioma/patient/mesothelioma-treatment-pdq. Accessed on February 15, 2016
  41. ↑ Savic S, Franco N, Grilli B, Barascud Ade V, Herzog M, Bode B; et al. (2010). "Fluorescence in situ hybridization in the definitive diagnosis of malignant mesothelioma in effusion cytology". Chest. 138 (1): 137–44. doi:10.1378/chest.09-1951. PMID 20139227.
  42. ↑ Chemotherapy for mesothelioma. Canadian cancer society 2016. http://www.cancer.ca/en/cancer-information/cancer-type/mesothelioma/treatment/chemotherapy/?region=on. Accessed on February 8, 2016
  43. ↑ Treatment of mesothelioma. Canadian cancer society 2016. http://www.cancer.ca/en/cancer-information/cancer-type/mesothelioma/treatment/?region=on. Accessed on February 8, 2016
  44. ↑ Surgery for mesothelioma. Canadian Cancer Society 2016. http://www.cancer.ca/en/cancer-information/cancer-type/mesothelioma/treatment/surgery/?region=on. Accessed on February 9, 2016
  45. ↑ Treatment of pleural mesothelioma. Canadian cancer scoiety 2016. http://www.cancer.ca/en/cancer-information/cancer-type/mesothelioma/treatment/pleural-mesothelioma/?region=on. Accessed on Februray 10, 2016
  46. ↑ Treatment of peritoneal mesothelioma. Canadian cancer society 2016. http://www.cancer.ca/en/cancer-information/cancer-type/mesothelioma/treatment/peritoneal-mesothelioma/?region=on. Accessed on February 12, 2016
  47. ↑ Asbestos. Wikipedia 2016. https://en.wikipedia.org/wiki/Asbestos. Accessed on February 16, 2016
  48. ↑ OSHA Archive. UniteD States Department of Labor 2016. https://www.osha.gov/pls/oshaweb/owadisp.show_document?p_id=246&p_table=TESTIMONIES. Accessed on February 16, 2016
  49. ↑ Finding mesothelioma early. Canadian cancer society 2016. http://www.cancer.ca/en/cancer-information/cancer-type/mesothelioma/finding-cancer-early/?region=on. Accessed on February 15, 2016


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