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Mesothelioma
Holli K. Neiman-Hart, MD, FAAFP
image BASICS
DESCRIPTION
  • Mesothelioma is a rare, aggressive malignancy of the mesothelial or serous tissues primarily found in the pleura (65-70%) or peritoneum (20-33%), tunica vaginalis (1-2%) or pericardium (1-2%) (1).
  • Inhalation of asbestos is the predominant cause of mesothelioma, most often from occupational exposure.
EPIDEMIOLOGY
Incidence
  • The incidence in the United States is decreasing, but it is increasing in other countries, particularly Great Britain and Australia.
  • It is expected that rates of mesothelioma will start to drop after 2015 to 2025 related to reduced exposure and better understanding of the process of development of mesothelioma after exposure to asbestos (2).
  • The incidence increases with age, peaking in the 6th decade, with 70% of pleural disease occurring in males. Peritoneal involvement is slightly higher in women.
  • Main risk factor is asbestos exposure, but tumors have arisen after prior radiation or exposure to talc, erionite or mica, or in patients with familial Mediterranean fever and diffuse lymphocytic leukemia.
Prevalence
There are 3,300 cases of mesothelioma diagnosed in the United States annually (3).
ETIOLOGY AND PATHOPHYSIOLOGY
  • The predominant cause of mesothelioma is exposure to asbestos (hydrated magnesium silicate fibrous minerals).
  • There is a long latent period of up to 44 years between exposure and development of mesothelioma (2).
  • Inhaled or ingested asbestos fibers become trapped in pleural or peritoneal membranes causing changes of irritation and inflammation.
Genetics
Loss of nuclear deubiquitinase BAP1 is associated with incidence of mesothelioma in some families as well as with other cancers such as melanoma.
RISK FACTORS
  • The predominant risk factor is exposure to asbestos.
  • Occupational exposures involve mining or milling of fibers, work with textiles, cement, friction materials, insulation, or shipbuilding.
  • Nonoccupational exposures include renovation or destruction of asbestos-containing buildings, exposure to industrial sources in the community or natural geologic sources, or exposure to soiled clothing of asbestos workers (1,3,4).
  • Radiation exposure, smoking, proximity to naturally occurring asbestos deposits, or inhalation of other fibrous silicates can contribute to malignant mesothelioma.
GENERAL PREVENTION
  • Avoidance of asbestos exposure
  • Strict adherence to protective protocols for workers in buildings where asbestos is found.
  • Continued aggressive remediation of asbestosaffected buildings and homes
image DIAGNOSIS
PHYSICAL EXAM
  • Pulmonary findings of decreased breath sounds, dullness to percussion, asymmetric chest wall expansion
  • Abdominal findings include distension, fluid wave with ascites, and tenderness.
DIFFERENTIAL DIAGNOSIS
  • Pleural mesothelioma differential diagnosis includes inflammatory reactions (empyema, pleural effusion), metastatic tumor from other sites, fibrosarcoma, malignant fibrous histiocytoma, sarcomatoid carcinoma, or synovial sarcoma.
  • Peritoneal mesothelioma differential diagnosis includes peritoneal carcinomatosis, serous peritoneal carcinoma, ovarian carcinoma in women, lymphomatosis, tuberculous peritonitis
DIAGNOSTIC TESTS & INTERPRETATION
Initial Tests (lab, imaging)
  • At present, there is no tumor marker or serum chemistry that is of value in establishing the diagnosis of mesothelioma.
  • Biomarkers that may be elevated in mesothelioma include fibulin-3, mesothelin, and osteopontin. However, they do not have an established role in diagnosis or monitoring response to therapy (2)[A].
  • Pleural mesothelioma diagnosis requires tissue. Thoracentesis for cytology and closed pleural biopsy may be adequate, but often, more invasive procedures such as video-assisted thoracoscopic surgery (VATS) is needed to obtain an adequate specimen (1,2)[A].
Follow-Up Tests & Special Considerations
Seeding of biopsy sites and tracks may occur in mesothelioma, which can be prevented with prophylactic radiation therapy to the scar or biopsy site (5)[A].
Diagnostic Procedures/Other
  • CT, MRI, PET, or integrated PET-CT helps with clinical staging in pleural and peritoneal disease (1,2,3,4),(5)[A].
  • Mediastinoscopy, bronchoscopy, and laparoscopy can assist in full surgical staging of pleural disease (2)[A].
  • Endobronchial ultrasound for staging is under investigation for pleural disease.
Test Interpretation
  • The tumor, node, metastasis (TNM) staging system is most commonly used although some centers use other staging systems.
  • Butchart staging system is the oldest and still used in some parts of the world.
  • Brigham staging system attempts to define resectability and lymph node involvement.
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image TREATMENT
GENERAL MEASURES
  • A multidisciplinary team is important in management and should include thoracic surgery, oncology, pathology, pulmonary, and radiology for patient specific planning of management.
  • Pain assessment and control should follow principles of cancer pain management (5).
MEDICATION
First Line
  • In pleural disease, combined therapy with cisplatin + gemcitabine or cisplatin + pemetrexed are associated with longer median survival than cisplatin alone (2),(4)[A].
  • Vinflunine is showing some potential for first-line treatment in pleural disease (2)[A].
  • Hyperthermic intraoperative or early postoperative intraperitoneal chemotherapy can decrease increase drug concentration to the peritoneum and decrease systemic side effects. Use cisplatin, mitomycin C, fluorouracil, doxorubicin, and/or paclitaxel (1,2),(3)[A].
Second Line
  • Palliative benefit in pleural disease with mitomycin C, vinblastine, cisplatin, and pemetrexed alone or in combination with carboplatin (2,3),(4)[A]
  • Systemic therapy for peritoneal disease may include pemetrexed + cisplatin; vinorelbine or gemcitabine alone or in combination (1),(5)[A].
ISSUES FOR REFERRAL
  • Pulmonary, oncology, and surgical follow-up after discharge as indicated
  • Anger and depression may require psychological or psychiatric services (5).
ADDITIONAL THERAPIES
  • Immunotherapy in pleural disease uses humanized anti-CB3 AB (OKT3), cytotoxic T lymph (CTL), interferon &agr;-2a, and autovaccine in advanced disease (1,2,3,4,5).
    • Gene therapy
    • Photodynamic therapy
    • Radiotherapy in some cases of pleural disease
    • Vascular endothelial growth factor (anti-VEGF-2) in combination with chemotherapy (2)
      • Vaccines are under study (5).
SURGERY/OTHER PROCEDURES
  • For pleural mesothelioma, the role of surgery is not as clear cut. Pleurectomy with tumor decortication and extrapleural pneumonectomy reduce the tumor load, but there remains no clear effect on mortality (2,4,5).
  • Radical resection of the peritoneum and cytoreductive surgery is associated with a better prognosis (1).
INPATIENT CONSIDERATIONS
Admission Criteria/Initial Stabilization
Based on overall condition
IV Fluids
As indicated by general condition
Nursing
As indicated by condition
Discharge Criteria
As indicated by general condition
image ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
  • Smoking cessation
  • Immunization for pneumococcal pneumonia and influenza
Patient Monitoring
Monitor for paraneoplastic phenomenon including fever, thrombocytosis, malignancy-related thrombosis, hypoglycemia, and rare Coombs-positive hemolytic anemia.
DIET
No specific restrictions
PROGNOSIS
  • Prognosis is based on gender, stage, and level of completeness of cytoreduction.
  • Poorly differentiated tumor grade, failure to undertake surgical resection, advanced age, and male gender are all independent predictors of poorer prognosis (2,3).
  • Average survival is 17 to 92 months, with 5-year survival rate at 63%.
REFERENCES
1. Bridda A, Padoan I, Mencarelli R, et al. Peritoneal mesothelioma: a review. MedGenMed. 2007;9(2):32.
2. Weder W. Mesothelioma. Ann Oncol. 2010;21(Suppl 7):vii326-vii333.
3. Mott FE. Mesothelioma: a review. Ochsner J. 2012;12(1):70-79.
4. Fuhrer G, Lazarus AA. Mesothelioma. Dis Mon. 2011;57(1):40-54.
5. van Meerbeck JP, Scherpereel A, Surmont VF, et al. Malignant pleural mesothelioma: the standard of care and challenges for future management. Crit Rev Oncol Hematol. 2011;78(2):92-111.
Codes
&NA;
ICD10
  • C45.9 Mesothelioma, unspecified
  • C45.0 Mesothelioma of pleura
  • C45.1 Mesothelioma of peritoneum
Clinical Pearls
&NA;
  • Mesothelioma remains a rare but universally fatal disease in part due to long latency.
  • Multimodal treatment has decreased recurrence rates and has extended survival time.