• Malignant Mesothelioma is a rare and aggressive cancer that originates from the mesothelial lining of organs.
• Commonly affects the pleura (lungs) but can also occur in the peritoneum (abdomen), pericardium (heart), and testes.

• Primarily caused by asbestos exposure in industrial settings.
• There is a typical latency period of 20-40 years between exposure and disease development.

• Mostly affects the pleura (80-90% of cases), with the right lung more commonly affected than the left.
• Metastasis is rare but may spread locally or to the peritoneum or opposite lung.
• Prognosis is poor due to the cancer’s aggressiveness and limited treatment options.

• Types:
– Pleural (most common)
– Peritoneal
– Pericardial
– Testicular

• The primary cause is exposure to asbestos fibers, which are inhaled or ingested, accumulating in the mesothelial linings of organs like the lungs, abdomen, heart, or testicles.

• Asbestos fibers cause chronic inflammation and induce genetic mutations, which over time lead to cancer development in the affected mesothelial tissues.

• Other factors include genetic susceptibility and radiation treatments, but these play a less significant role compared to asbestos exposure.

• Primary Risk Factor: Asbestos exposure is the most significant risk factor.
– High-risk occupations: Construction, mining, shipyards, asbestos manufacturing
– Environmental exposure: Living near asbestos industries or having family members who work with asbestos
– Exposure details: The risk increases with the duration and intensity of exposure.

• Other Risk Factors:
– Radiation therapy: Previous exposure to radiation, particularly to the chest area
– Genetic factors: Certain genetic mutations and inherited conditions can elevate the risk.

• Originates from mesothelial cells lining organs.
• Asbestos exposure leads to chronic inflammation and DNA damage.
• Genetic mutations accumulate over time.
• Results in uncontrolled cell growth and formation of cancerous tumors.

• Tumors invade nearby tissues
• Spread to regional lymph nodes
• Metastasis to distant organs

• Tumor growth and spread involve multiple molecular pathways.
• Involves interactions between tumor cells and the microenvironment.

• Lung cancer
• Metastatic cancer
• Benign asbestos-related diseases (e.g., asbestosis)
• Other pleural tumors (e.g., solitary fibrous tumor)

• Increasing incidence due to past asbestos exposure, especially in industrial sectors.
• Primarily affects men, with nearly half of cases in people aged 75 and above.
• Incidence in UK males: 3.4 per 100,000, with about 2700 new cases annually.
• Latency period can extend up to 50 years between asbestos exposure and diagnosis.
• Rising incidence observed due to delayed diagnosis and historical asbestos use.
• Occupational asbestos exposure accounts for over 80% of cases, but only 20% show pulmonary asbestosis.

• Chest pain
• Shortness of breath
• Cough
• Fatigue
• Weight loss
• Abdominal pain or swelling (in peritoneal mesothelioma)
• Testicular mass or swelling (in testicular mesothelioma)
• Nonspecific symptoms that may mimic other conditions include anorexia, dry cough, and fatigue
• Late diagnosis is common due to a lack of specific early symptoms

• Dyspnea (shortness of breath)
• Weight loss
• Chest wall pain
• Finger clubbing (often due to underlying asbestosis)
• Painless pleural effusion (present in 30% of cases)
• Only 20% of cases have pre-existing asbestosis
• 85-90% of cases have a history of asbestos exposure
• Latent period of 30-40 years between asbestos exposure and symptom onset

• Typically presents in the sixth to ninth decade of life with advanced disease.
• Strongly associated with environmental asbestos exposure
• Risk factors include family history (BAP-1 mutations) and radiation exposure
• Diagnosis requires a thorough history, including asbestos exposure and high-risk occupations
• Specific symptoms related to intrathoracic disease: shortness of breath, dry cough, chest pain
• Physical findings often related to pleural effusions: decreased breath sounds, reduced chest expansion, dullness to percussion
• Abdominal distension may indicate malignant peritoneal mesothelioma or intra-abdominal extension of pleural mesothelioma

• Imaging Studies: Chest X-ray, CT scan, MRI, PET scans
• Biopsy: Biopsy of affected tissue to confirm diagnosis and determine histological subtype
• Immunohistochemical staining to confirm mesothelial markers and rule out other malignancies
• Additional Tests: Blood tests (e.g., mesothelin-related biomarkers), pleural fluid analysis to aid in diagnosis and assess disease extent

• Initial Suspicions: Raised by chest X-ray showing pleural effusion or pleural thickening
• Diagnostic Steps:
– Pleural CT scan
– Fluid analysis: MC&S, biochemistry, cytology (helpful in only 20-30% of cases)
– Local anesthetic thoracoscopy for cytology-negative exudative effusions (high diagnostic yield around 95%)
– Image-guided pleural biopsy if pleural nodularity is seen on CT
• Imaging Findings:
– CXR and CT scan with contrast may show pleural effusion, pleural thickening, pleural mass, or rib destruction
– MRI and PET scans may also be performed
• Pleural Fluid Analysis: Straw-colored or bloodstained
– Cytological analysis occasionally leads to diagnosis
– Pleural biopsy (ultrasound or CT-guided percutaneous biopsy) usually required for confirmation
• Other Investigations: PET scanning for regional or distant disease assessment, pulmonary function tests (FEV1 and DLCO) for surgical evaluation

• Stage Ia: T1a N0 M0: Primary tumor limited to ipsilateral parietal pleura
• Stage Ib: T1b N0 M0: Stage Ia criteria plus focal involvement of visceral pleura
• Stage II: T2 N0 M0: Criteria of Stage Ia or Ib plus confluent involvement of diaphragm, visceral pleura, or lung involvement
• Stage III: Any T3 M0: Locally advanced tumor
– Any N1 M0: Ipsilateral bronchopulmonary or hilar lymph node involvement
– Any N2 M0: Subcarinal or ipsilateral mediastinal lymph node involvement
• Stage IV: Any T4: Locally advanced, technically unresectable tumor
– Any N3: Contralateral mediastinal, internal mammary, and ipsilateral or contralateral supraclavicular lymph node involvement
– Any M1: Distant metastases

• Symptomatic Management: Focus on managing symptoms as a cure is usually only possible with surgery for extremely localized (stage I) cases
• Palliative care: Crucial for improving quality of life and providing supportive care
• Industrial Compensation: Explore options for individuals exposed to asbestos in the workplace
• Prognosis: Generally poor with a median survival of 12 months

• Surgery: Used for diagnosis, staging, and treatment; includes extrapleural pneumonectomy and lung-sparing debulking procedures. Best outcomes reported when combined with multimodality treatment achieving macroscopic complete resection (MCR)
• Chemotherapy: Crucial in both preoperative (potentially resectable) and palliative settings, especially for unresectable cases. Platinum-based chemotherapy (e.g., cisplatin, carboplatin) is a cornerstone
• Radiotherapy: Used for local control reduction, post-surgical adjuvant therapy, or pain control in specific cases

• Surgical Approaches: Includes extrapleural pneumonectomy (removal of pleura, ipsilateral lung, pericardium, and hemidiaphragm) and pleurectomy with decortication (removal of pleura from the chest wall and other structures)
• Radiotherapy: Post-extrapleural pneumonectomy radiotherapy for local/regional tumor growth or as adjuvant therapy
• Palliative Procedures: Thoracocentesis and pleurodesis for symptomatic relief; pleurodesis performed to prevent pleural fluid re-accumulation, often using talc

• Poor prognosis due to the cancer’s aggressiveness and limited treatment options.
• Prognosis depends on factors such as:
– Disease stage
– Tumor location (pleural, peritoneal, etc.)
– Cell type
– Overall health
– Response to treatment

• Average survival ranges from 6 to 18 months (median).
• Early detection, aggressive treatment, and specialized care can extend survival.
• Better prognosis for peritoneal mesothelioma compared to pleural.
• Advanced stage, older age, poor health, and specific subtypes are linked to a poorer prognosis.

• Survival typically around one year for malignant pleural mesothelioma.
• Prognosis influenced by:
– Age
– Staging
– Histology
– Performance status
• England’s 10-year+ survival (2013-2017) was 2%.
• Regular monitoring, follow-up care, and support are crucial for symptom management and optimal care.

• Complications vary by the affected organ and stage of the disease, including:
– Respiratory insufficiency
– Pleural effusion
– Infection
– Pain and dyspnea
– Cachexia (severe weight loss)
– In advanced stages, organ failure and related complications may occur

• Treatment-related complications include:
– Surgical complications
– Chemotherapy-induced toxicity
– Radiation-related issues

• Palliative care aims to:
– Alleviate symptoms (e.g., pain, dyspnea)
– Improve quality of life
– Manage complications related to both the disease and its treatment