Dr. Prasanth Sankar

Prof. Dr. E. Dhandapani’s Unit

Ramu38/m Thiruvannamalai

C/oLeft sided chest pain

6 moBreathlessness

H/o breathlessness – 6 mo

Progressively increasingInitially on exertion, later on at

restMore on lying on right sideNo PND, orthopneaSevere for the last 6 days

• Left sided Chest PainPleuritic type initiallyLater on persistant, aching and pricking

typeMore on the lateral aspect of L chestNot assoc with palpitation, sweatingwith coughing and lying on left sideCough Mostly non productiveOccasional expectoration of mucoid

sputumNon purulent; No hemoptysis

Gradual restriction of movements of L chestPainful Swelling -Lateral side of L chest-3

wksH/o loss of weight -6-8 kg/6moH/o Loss of Appetite +No h/o

CyanosisLeg swelling, Abdominal distensionFeverOliguriaGiddiness, LOCChest Trauma

Evaluated for symptoms at local

hospitalBased on X ray findings – empirical

ATTSymptoms continued to progressDiscontinued ATT after 3 moAttended CT OP at GSH- adv CT chestSevere dyspnea at rest -6 daysReferred from local hospital to GSH

No history S/oBronchial Asthma,

COPD, TB, Radiation ExposureHeart disease/

HTN/DM/CKDTrauma/

interventionsConnective tissue

disorders

Smoker – beedis – 25 pack yrs

Consumes alcohol once/twice per week

No high risk behaviour

Manual labourer – rice godown

Personal History

G/E-

Conscious , OrientedModerate built & poorly nourishedSeverely Dyspneic, Tachypneic, restlessDifficult to speak in sentencesNo pallor, icterus, cyanosis, clubbing,

edemaNo significant lymph nodesBP – 110/70Pulse – 108/min, regularRR – 34/min SpO2 – 88% (room air)JVP – not raised

RSTrachea – marked left shiftMarked scoliosis of thoracic spine- concavity

to LeftSevere crowding of ribs left side, Dilated

veins +Chest movements markedly restricted on L

side5X3X2cm tender firm swelling over Left 7,8,9

interspacesImmobileTendernss of surrounding areas of chest wallNo sinuses,non pulsatile

Dull/ stony dull percussion note - LeftHyper-resonance - Right VF/VR - Left BS markedly dimnished L hemithoraxNo adventituous sounds

CVSApex not localisedS1, S2 +

Abdomen, CNS - WNL

PT sequelaeLeft pleural fibrosisMalignancy

Shifted to IMCW

O2 inhalation/Propped up positioningBronchodilatorsAntibioticsAnalgesicsIV FluidsSupportives

With TreatmentMild improvement of symptomsSpO2 – 95-96%

Hb -10.5PCV - 35TC -9800DC – P44/L53/E3PLT – 2.1LESR-10/22RBS – 121 Urea -24 Creat –

0.8Na – 135 K – 3.4

LFT – WNLBT/CT/INR – WNLRUE – WNLHIV/VDRL - negativeECG – Sinus tachycardia, P pulmonaleSputum

GS & AFB – negativeCulture – no growthCytology – no malignant cells.

CXR-CT chest-

CTS opinion

imp: Pleural Mesothelioma Adv: CT guided biopsy

Medical oncology:imp: Mesothelioma Stage IVAdv: CT guided/open Biopsy

Review with results

CT guided biopsy was fixed in GHPatients dyspnea and chest pain

persistedSpO2 – 92-94% with O2On 4th day of admission..patient went

into sudden cardiac arrestResuscitated and recovered.Intubation-Mechanical Ventilation

givenAgain went into cardiac arrest &

expired..

Malignant Mesothelioma - Stage IV

Uncommon but no longer be considered

rare.3000 cases/year diagnosed in the US alone. In countries where control of asbestos was

delayed by several decades, the “epidemic” of mesothelioma will also be delayed by several decades

Asbestos continues to be mined, and its use is actually increasing in many developing countries

Asbestos industryInsulators PipefittersShipyard workers Brake mechanics Railroad workersConstruction

trades CarpentersPlumbersElectricians

PaintersNon-asbestos

minersWeldersMachinistsManufacturers of

mineral productsMaintenance and

repair in buildings with asbestos insulation.

Women with asbestos-induced

mesothelioma -only clear asbestos exposure was from exposure to their spouses' contaminated clothing.

Children incidentally exposed -develop mesothelioma in early adult life.

Incidence may rise - dust that settled after the collapse of the World Trade Center

Of nanoparticles and nanotubes raises concerns

Simian virus (SV40) – animal studies

Oil refinery workers-petroleum oil and its products ?

Cigarette smoking and Silica- -not associated with increased incidence of mesotheliomas

Radioactive contrast medium thorotrast Therapeutic radiation for of lymphoma or breast

Ca.

In turkey, -exposure to erionite dust, a non-asbestos crystalline fibrous form of the mineral zeolite.

Chronic inflammation of the pleura as in familial mediterranean fever

Although millions exposed, only a few develop

mesotheliomaHigh degree of aneuploidy, but no single

oncogene or tumor suppressor gene found culprit

p16INK4A-p14ARF(9p21), (NF2) gene (22q12)P53 & Kras – not mutated1p, 3p, 6q, 9p, 15q, and 22qGrowth-promoting genes – PDGF, EGFRlong latency period-multiple genetic

abnormalities

Constitutional symptoms

Weight loss (30%), cough (10%) and fatigue are not common in the early presentation.

HPOA and intermittent hypoglycemia are unusual

Serous effusionsMost common presentation - 95%Dyspnoea (40–70%)Non-pleuritic chest pain (60%)

Local invasionDirect invasion of adjacent structures is

characteristic of malignant mesothelioma.SVC obstruction, Spinal cord compression,Horner’s syndrome, oesophageal compression, Chest wall masses, Malignant pericardial

disease.Metastasis along tracks of previous

invasive procedures (2 – 51 %)Chest wall, rib or intercostal nerve- pain. Pericardial invasion- pericardial effusion,

cardiac tamponade and/or arrhythmias, Invasion into c/l hemithorax or peritoneal

cavity

Distant spread

Extrathoracic spread- 54–82% PMOften clinically silent and rarely cause of

deathHilar or mediastinal lymph node

metastasis -44%Intracranial metastases-3%‘Miliary mesothelioma’- rare.

Pleural effusion or pleural mass Large effusions or tumour masses-

mediastinal displacement.Tumour may erode through chest wall and

cause localised tenderness and/or palpable masses

Spread within the pleural cavity - ‘fixed’ hemithorax, with reduced chest expansion.

Signs of compression or invasion of mediastinal structures.

Signs of extrathoracic involvement are uncommon

Clubbing of fingers -not a feature

Unilateral pleural effusion with or

without evidence of pleural thickening

Occasionally-large visible mass at presentation

Pleural thickening and encasement of the underlying lung may neutralise the mediastinal shift contracture of the affected hemithorax.

Pleural plaques and asbestosis - (20%)

Rind-like tumor extension on pleural surfaces -

70%Circumferential encasement by multiple nodules -

28%Pleural thickening with an irregular margin

between the lung and the pleura - 26%Pleural thickening;pleural-based nodules - 20%Invasion of soft tissues & chest wall with rib

erosionLung encased with tumor, volume loss with a shift

of mediastinum toward side of primary tumor Signs of lymphatic metastasis – lateMediastinal adenopathy – very rare

CT features that favor diagnosis of

malignant mesothelioma over metastatic pleural disease Rind like pleural involvement, Mediastinal pleural involvement, and Pleural thickness more than 1 cm

MRI may demonstrate extent of disease and in particular chest wall and diaphragmatic invasion better than CT

FDG-PET and particularly PET/CT -differentiate benign from malignant disease and as adjunctive tools for staging

No specific haematological or biochemical test

Anemia, thrombocytosis, high ESR, hypergammaglobulinaemia.

Only serum biomarker clinically useful is serum mesothelinHigh specificity (>90%).

But only a 50% sensitivity for the diagnosis.

Thoracocentesis - difficult to distinguish

between reactive mesothelial cells and malignant ones.

Aspirate cytology of effusions - 33% to 54%Pleural fluid Mesothelin – useful biomarker.Closed pleural biopsy – sensitivity of 55% CT-guided biopsy – sensitivity of 88% Accuracy - morphologic appearance and

results of tumour marker staining using light microscopy

Preferred technique -surgical

biopsy via pleuroscopyLarge samplesDrainage of effusionsFreeing up of a trapped

lungTalc pleurodesis if lung not

trappedBronchoscopy, BAL and Ga

scan-no useful role

Median survival- 4 -12 mo from the time of

diagnosisEpithelial cell type do best and those with

the sarcomatous cell type the worstPoor Prognosis

Age, male gender, performance status, leukocytosis, and chest painmicrovessel densitytumor necrosis

Surgical Therapy - Debulking

Pleurectomy with Decortication (P/D)Extrapleural Pneumonectomy (EPP)Epithelial cell type, clean margins after

resection, and negative lymph nodesTumor debulking using EPP followed by

chemotherapy and high-dose radiation therapyChemotherapy

Pemetrexed – CisplatinumGemcitabine with a platinum agent

Radiation TherapyLimited to adjunctive therapy

Drugs

Gefitinib and ImatinibThalidomideSuperoylanilide hydroxamic acid (SAHA)-

histone deacetylase inhibitorProteasome inhibitorsBevacizumab

ImmunotherapyIntrapleural interferon-γInfusion of interleukin-2

Gene Therapy

Palliative Therapy

Pain managementPleurodesisPlacement of a tunneled pleural catheter

Chemoprevention and ScreeningScreening of high-risk populations Sensitivity of serum mesothelin is not sufficient

for use as a marker Daily vitamin A (retinol) or β-carotene - trialRoutine low-dose CT scanning - trials

1. 2010 – Murray and Nadel's Textbook of Respiratory Medicine, 5th ed

2. 2010 – Pleural Disease- Second Edition

3. 2008 – Fishman’s Pulmonary Diseases and Disorders-Fourth Edition

4. 2002 – Mesothelioma

5. 2002 – Crofton And Douglas’s Respiratory Diseases – Fifth Edition