EPIDEMIOLOGY

Although lung cancer is a malignancy ofincreasing age, with 70% of cases occur-ring in over 65-year-olds, it represents asignificant socio-medical burden. In thedeveloped world it has become the com-monest cause of cancer death in men. Inthe UK it represents 1 in 3 cancer deathsand 25% of cancer registrations. Inwomen it is the most rapidly rising causeof cancer mortality and is now secondonly to breast cancer. In Scotland it evenexceeds breast cancer mortality, withlung cancer causing annually the loss ofover 51 500 life-years compared with21 000 life-years for breast cancer.

PATHOGENESIS

TobaccoThe great potential for primary preven-tion in lung cancer is self-evident.Around 90% of lung cancer is attribut-able to cigarette smoking. Rates in menin the developed countries are fallingslightly concomitant with reductions insmoking: in contrast to those seen inwomen. The evidence implicating pas-sive smoking in the genesis of lungtumours is not as robust. Very fewpatients (< 10%) are true ‘never smok-ers’.

Tobacco smoke contains over 40 dif-ferent oxidants and carcinogens, includ-ing benzpyrenes, acrolein and benzene. Insusceptible patients these cause neoplasticchange at the bronchial epithelium.Despite exposure of the whole mucosa toinhaled compounds, the development oftumours is usually focal. The activationof tumour promoting genes and inhibitionof tumour suppressor genes (includingp53, see box) occurs. Depending on thehost’s immunological response, cell

reproduction may continue with this lossof normal cellular growth and differentia-tion mechanisms. This results in a macro-scopic tumour (Fig. 1). Hence, thesubstantial rise in lung cancer that we arestill seeing reflects the widespread uptakeof cigarette smoking earlier in the lastcentury. Even a complete cessation nowof smoking would take many years to seean effect on lung cancer.

That only 20% of cigarette smokersdevelop lung cancer demonstrates therole of inter-individual factors thatinclude:

• Genetics.Non-smokers with a familyhistory of lung cancer are at greaterrisk compared to non-smokerswithout a pedigree.

• Environment. Rural populationsusually have lower incidence ratesthan urban communities.

• Social deprivation.Communitiesscoring highly for social deprivationshow higher rates than less deprivedareas, even when corrected forcigarette consumption. Deprivationmay be a surrogate for factors such asdietary intake of antioxidant vitaminsand minerals.

Other causesAsbestos is an inert natural rock silicatewith uses in industry. Unfortunately, it isalso a carcinogen in its own right. Therisk of exposure to asbestos is synergisticwith tobacco smoke. To a non-smokerthe risk of lung cancer from asbestosexposure is five times that of an unex-posed non-smoker, while in a smokingworker the exposure risk is 55 times thatof an unexposed non-smoker. Other occu-pational causes of lung cancer include theinhalation of radioactive gases, includingenvironmental exposure to radon, and

workplace chemicals that includearsenic, chromate and those of the elec-tronics industries.

CLINICAL PRESENTATION

Clinical presentation is usually late in thetumour’s natural history. Furthermore,co-morbidity in an aged and largelyuncomplaining group of patients con-tributes to the poor survival rates.Overall, a mere 8% of diagnosed patientswill survive 5 years, a rate that haschanged little in the past three decades.The current poor outlook for patientswith this disease might be improved by ahigh index of clinical suspicion for ear-lier diagnosis to offer more patientspotentially curative surgery. Barely 20%of patients at presentation have diseasesufficiently localised for attempts atcurative surgery.

SCREENING

The combination of a readily identifiablepopulation at increased risk of develop-ing lung cancer and such poor survivaldue in part to late presentation wouldsuggest a need for screening pro-grammes. However, programmes utilis-ing chest radiography and sputumcytology in a number of healthcare sys-tems around the world have been disap-pointing. There has been no objectiveevidence of a survival benefit in any ofthese screened populations.

CLASSIFICATION

Clinically and pathologically, it is usefulto consider malignant lung tumours aseither small (undifferentiated) cell lung

LUNG CANCER I

RESPIRATORY DISEASE ⟩ NEOPLASTIC DISEASE54

Activation of tumourpromoting genes

Inactivation of suppressorgenes

Growth factors enhancing

Host immune response

Continued cell division andloss of differentiation

New blood vessel strands

Invasion and desimination

Molecular changes Carcinoma in situ Invasive malignancy

Fig. 1 The development of lung cancer.

Fig. 2 Cytological examination of early morningsputum with malignant (orange and greenstaining) squamous cells. (Image courtesy ofDr G. Rebello.)

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be aspirated and washings, needleaspiration or brushings obtained forcytology with mucosal biopsies forpathology. A partial assessment ofthe suitability of the patient forsurgery can also be made.

• Pleural aspiration and biopsy in thepresence of pleural fluid and hencepossible pleural deposits of tumour.

• Needle aspiration of neck nodes forcytology.

• Transthoracic needle aspiration orbiopsy of subpleural masses (Fig. 4).

• Thoracoscopy and biopsy of pleural,mediastinal or subpleural pulmonarymasses.

• Liver or bone biopsy of possibledeposits.

cancer (SCLC, about 20% of lung can-cers) or non-small cell lung cancer(NSCLC).

SCLCThis can be diagnosed with a high degreeof confidence, even cytologically. It typi-cally presents as a bulky central lungtumour with early spread to mediastinumand to extrathoracic sites. The tumourcells proliferate rapidly and untreatedpatients have a median survival of a mere3–4 months from presentation.

NSCLCNSCLC covers a heterogeneous group.Pathologists recognise:

• squamous cell carcinomas(now about 20–25%)

• adenocarcinoma (40%)• undifferentiated (non-small cell)

carcinomas • truly mixed tumours.

These tumours may be more difficultto type with confidence on cytology orsmall biopsy specimens, hence the use-fulness of NSCLC as a classification.Adenocarcinomas have increased in fre-quency over the last 2–3 decades. Inrecent US and UK studies outsideethnic Chinese populations, adenocarci-noma is now the most common form ofNSCLC. SCLC is also increasing as aproportion of all lung cancer. Thesechanges may reflect the increase inwomen smokers and changes in the typeand burning qualities of current tobacco.

PATHOLOGICAL DIAGNOSIS

The majority of patients need the clinicalor radiological suspicion of lung cancerto be pathologically confirmed. There isalways a balance between what is possi-

55

Lung cancer I• Lung cancer is the most common

solid tumour affecting males inwestern Europe.

• Tobacco smoking is the major andmost easily preventable, but not thesole, risk factor.

• Clinical presentation is often late;the diagnosis may not be readilyapparent, a factor contributing to poorsurvival rates over the last threedecades.

p53 and cigarette smoke

The human gene called p53 is a tumour suppressor gene that initiates programmedcell death in malignant cells. Specific point mutations in p53 preventing cell deathare common in human cancers, particularly lung tumours. Tobacco smoke con-tains a carcinogen benzo[a]pyrene, a metabolite of which has been demonstratedto cause at least one of these specific mutational changes to p53 gene in a numberof experimental cell types. There may well be other carcinogens which producespecific mutations in this or other tumour suppressor genes. This provides the firstmolecular evidence directly linking cigarette smoke with the genesis of lung cancer. Control of such gene activity may be an avenue for future anti-tumour therapies.

LUNG CANCER I

Case history 24

A 50-year-old man presents withpain in his left hip of gradual onsetover days. He has a central mass onhis chest radiograph.

• How would you confirm yoursuspicion of lung cancer?

• Why does he have bone pain?

• Blood results demonstrateNa:122; Ca: 2.6; alb 34; alk phosphate: 650. Why?

ble and what is therapeutically appropri-ate for an individual patient. Techniquesavailable include:

• Cytological examination of earlymorning sputum (Fig. 2). This maybe more readily obtainable and is lessinvasive than bronchoscopy forcentral airway disease. Threeadequate samples on consecutivemornings should be consideredstandard.

• Flexible bronchoscopy for centralendobronchial (Fig. 3) orperibronchial disease. Secretions canFig. 4 CT guided needle biopsy of lung mass.

Fig. 3 Flexible bronchoscopy.

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CLINICAL FEATURES

Less than 10% of patients are asympto-matic at presentation. These cases areoften discovered as a result of a chestradiograph performed for another reasonand usually present as a solitary periph-eral lesion (SPL). An SPL may be benignor malignant, primary or secondary (Fig.1). Benign disease, especially tuberculo-

sis granulomas or benign tumours,should always be considered. There areno radiological features absolutely char-acteristic of benignity, but the presenceof certain patterns of calcification, occur-rence at the site of known benign diseaseand previous radiology demonstratingslow if any change in size are all helpful.

An SPL is more likely to be malignantwith increasing age of the patient, partic-ularly if a smoker. If there is a knownprimary tumour elsewhere, or there isclinical evidence of one, the SPL is likelyto be a secondary. If the available evi-dence suggests a primary and the patientis fit, then curative resection should beplanned. This will provide histological

confirmation and potential cure at thesame time. Such a policy accepts finiteresection rates both for lesions that turnout to be benign (less than 5% and usuallytuberculosis), and for those that with thepassage of time become evident as sec-ondaries (up to 10% of adenocarcino-mas).

Primary tumoursOf the remaining presenta-tions, one-third have symp-toms due to the primarytumour. New cough or changein a long-standing cough,even without haemoptysis, isan important symptom in asmoker, even if a chest radi-ograph is normal. The conse-quences of large airwayobstruction (Fig. 2) that mayinclude inspiratory stridor,‘slow to radiologicallyresolve’ pneumonia, undue orworsening breathlessness that

may be difficult to distinguish from themany other causes.

MetastasesA further third of presentations are dueto intrathoracic (Fig. 3) or extrathoracic(Fig. 4) metastases.

Systemic symptomsThe remaining patients present due to

systemic symptoms. Weight loss mayresult from cytokines secreted by thetumour. Lassitude is also characteristic.

Non-metastatic or para-neoplasticmanifestations arise by the production ofcirculating factors derived from theprimary tumour, and may be apparent atinitial presentation or later. Treatment ofthe primary may not always alleviatethese manifestations. The common pat-terns are:

• Bone:—clubbing, rarely in SCLC—hypertrophic pulmonary

osteoarthropathy, painful wristsand ankles from new boneformation, usually squamous oradenocarcinoma.

• Endocrine:—ADH secretion, usually by SCLC

causing hyponatraemia thecommonest electrolyte upset;patients become confused,require fluid restriction anddemeclocycline

—non-metastatic hypercalcaemia,due to PTH-like substancessecreted usually by squamoustumours

—Cushing’s syndrome: rapid onsetwith weakness (myopathy andhypokalaemia) and hyperglycaemiafrom ectopic ACTH secretion.

LUNG CANCER II

RESPIRATORY DISEASE ⟩ NEOPLASTIC DISEASE56

Fig. 1 Solitary peripheral lesion.

Apical tumourand brachial

plexus erosion; arm pain

Rib depositand pain

Pleural effusion,breathlessness

Phrenic nerve palsyand diaphragm elevation

Hoarseness with recurrentlaryngeal nerve palsy

Lobar bronchus obstruction,lobe collapse, breathlessness,cough, haemoptysis

Lymphangitis,breathlessness

Pericardial infiltration,atrial fibrillation andtamponade

Central tumour• stridor• SVC obstruction and face swelling

Fig. 3 Intrathoracic spread of lung cancer with associated symptoms.Fig. 2 Airway obstruction by endobronchialtumour.

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57

Lung cancer II• The most useful clinico-pathological

classification is into SCLC andNSCLC.

• SCLC is an aggressive central tumourwith a median survival of 3 monthsuntreated.

• For many patients, symptom control isthe main therapeutic goal.

LUNG CANCER II

• Haematology: coagulopathy,disseminated intravascularcoagulation with a consumptivebleeding disorder or venousthromboses and superficial phlebitis.

• Neurology: rare syndromes in aspectrum from peripheral neuropathythrough myaesthenia todermatomyositis.

MANAGEMENT

SurgerySurgery for NSCLC, and probably forvery early SCLC, still offers the bestchance of cure, with a 5-year survival of50% in early stage NSCLC. This requiresa thorough clinical, laboratory and radio-logical assessment to ensure the patient isfit to withstand single-lung anaesthesiaand major surgery, along with an absenceof metastatic malignant disease outwiththe planned resection of lobe or lung.This usually requires:

• Pulmonary function to include FEV1FVC, Kco, walking distance, restingelectrocardiogram. Cardiac reservemay have to be assessed further witheither an exercise treadmill test orcoronary angiography.

• Biochemistry including calcium andliver enzymes.

• Plain radiology of chest.• CT scan of chest particularly to

Case history 25

A 50-year-old man has a bone sec-ondary from lung cancer. Bloodresults demonstrate: calcium 2–7mmol/l, albumin 34 g/l, alkalinephosphatase 650 u.

What treatment could youoffer?

Table 1 Quality of life – symptom-relievingstrategies in lung cancer

Breathlessness

Cough

Pain

Haemoptysis

Identify and treat conventionally heart failure, COPD,anaemia, etcPleural effusion• drain and pleurodeseLobar or main stem obstruction• radiotherapy

endoluminal tumourablation

• tracheobronchial stentLymphangitis• steroid trialRadiation pneumonitis• steroid trial‘Tumour associated’• breathing relaxation techniques• pacing activities• other non-pharmacological techniques such as

aromatherapy and acupuncture• liquid morphine• nebulised morphine• anxiolytic

Radiotherapy• external beam• intraluminal (brachytherapy)Endobrachial cautery argon plasma

Bone pain• non-steroidal analgesic and opiate• radiotherapyNeural pain• steroid• anticonvulsant, e.g. gabapentinAnorexia, weight loss• small frequent meal• increase spice/herb use• steroid• anti-inflammatory drug

Oral opiate

Nebulised lignocaine (with care)

identify mediastinal glands thatshould be sampled for histology.Many centres include CT of liver butultrasound is at least as good as CTand liver deposits are unlikely in theabsence of an elevated alkalinephosphatase.

Thoracic surgical teams will formallyexplore the mediastinum to sample nodesdirected by the CT scan before undertak-ing formal resection.

Alternative therapiesSurgical cure should be the goal in fitpatients with resectable NSCLC. Inpatients with resectable disease, but whodecline surgery or have intercurrent(usually cardiac) disease, radical radio-therapy may be an option with cure ratesnot that different from surgery. SCLCcan be treated with cyclical combinationchemotherapy, providing a median sur-vival of around 12 months with anincreased quality of life.

Palliative carePalliative care, in the broadest multidis-ciplinary sense, should begin at diagnosisand the breaking of that bad news to thepatient. Radiotherapy can palliate thesymptoms of bone pain, significanthaemoptysis, breathlessness from lobe orlung collapse consequent on airwayobstruction or impending collapse, supe-

rior mediastinal obstruction and spinalcord compression. Radiotherapy offerslittle for the non-specific symptoms oflassitude and weight loss. Newchemotherapy regimes even for inopera-ble NSCLC may help such symptoms.Control by pharmacological or non-pharmacological means of pain, cough andbreathlessness in particular are impor-tant. Metabolic disturbances includinghyponatraemia and hypercalcaemia canpresent insidiously, and should beactively sought. These will respond toappropriate therapy. Teflon injection of aparalysed vocal cord under local anaes-thetic can help voice quality. As survivalis in general poor, the quality of lifeshould be paramount in the managementof such patients.

Future therapiesAdvancements in understanding tumourdevelopment and cell biology will allow

Brain• meningeal infiltration–headache• confusion• paresis• fits

Cervical adenopathy

Liver deposits• pain from capsule stretch• jaundice

Adrenal deposits• common but rarely significant

Bone deposits• pain• nerve entrapment including cord• pathological fracture• hypercalcaemia

Fig. 4 Extrathoracic spread of lung cancer withassociated symptoms.

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METASTATIC SPREAD AND THELUNGHAEMATOGENOUS SPREAD

The lung, in receiving all of the cardiacoutput, is a common site for haematoge-nous tumour deposition, even secondaryspread from a lung primary. Other com-mon primary sites include gut (stomach,rectal), genitourinary, breast and malig-nant melanoma (Fig. 1). Pulmonarydeposits may be asymptomatic or appearbefore the primary is clinically apparent.Such haematogenous secondaries appearas discrete ‘cannon-ball’ masses enlarg-ing on chest radiographs over time (Fig.2). They tend to be subpleural and lowerzone. When small, secondaries need dif-ferentiation from benign granulomas onCT scanning. An isolated metastasisrequires differentiation from a primarylung tumour. A solitary secondary maybe considered for metastectomy eitherfor relief of symptoms or as a debulkingprocedure. There may be a worthwhiletime delay before further secondariesdevelop. Any other treatment must be governed by the primary tumour.

PLEURAL DEPOSITS

Pleural tumour deposits present aspleural effusions, rarely as discretepleural masses. Investigation by Abramsbiopsy or thoracoscopy should confirmthe diagnosis. Stomach, breast and ovar-ian tumours often spread to the pleura,with therapeutic gain in discovering pri-

rigid by a lattice-work of tumour withinthe lymphatics. If performed, CT scan-ning will demonstrate nodules of tumouralong a pattern of distended lymphatics.

ENDOBRONCHIAL SECONDARIES

These metastases that occur on theluminal side of the bronchi are rare.Those that occur in the central airwaysand, hence, are visible at bronchoscopyrepresent about 1 per 150 bronchoscopiesfor cancer (Fig. 4).

Most are found as an explanation forhaemoptysis or obstructing symptoms.Often there is a past history of theprimary cancer; colon and breast are themost common (Fig. 5).

RARE TUMOURS

Bronchioloalveolar cell carcinomaThis is a form of adenocarcinoma thathas a propensity for spread along thealveolar walls and into lymphatics.Insidious breathlessness, a cough pro-ductive of frothy sputum and a progres-sive pneumonia-like illness are usualpresentations. Chest radiology demon-strates alveolar shadowing (Fig. 6).Cytology of sputum or bronchoscopicwashings will confirm malignancy andbronchoscopic lung biopsy may demon-strate the characteristic pattern of alveo-lar wall spread. Often at diagnosis

METASTATIC SPREAD AND THE LUNG

RESPIRATORY DISEASE ⟩ NEOPLASTIC DISEASE58

Fig. 1 Haematogenous spread: whole lung pathology (a) and chest X-ray (b) of an individual withmalignant melanoma metastases in the lung.

(b)(a)

Fig. 2 Multiple, mainly peripheral and variable in size — these are the characteristic features of multipleblood-borne lung metastases.

mary tumours in the latter two sites (seepp. 66–67).

INTERSTITIAL LYMPHATIC SPREAD

Lymphangitis carcinomatosis has a sug-gestive radiological pattern of progres-sive interstitial shadowing, includingseptal and intrapulmonary (Kerley A)lymphatic lines (Fig. 3). The clinical pic-ture is of a patient, usually with a knownprimary, complaining of relentlessbreathlessness. Their distress is oftenseemingly out of proportion to the appar-ent plain X-ray abnormalities, butreflects the increasingly stiff lungs held

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distal to bronchialobstruction. Sleeveresection of thebronchial wall withthe tumour should

be curative.Histologically, ‘atypical carcinoids’

may present as above but tend to behavemore as malignant tumours with localand distant spread. They are chemosensi-tive. There is some morphological andembryological basis in considering aspectrum of behaviour from typical car-cinoid through ‘atypical’ to small celllung tumours.

Lymphangioleiomyomatosis (LAM)This is a malignancy of immature pul-monary smoothmuscle cells and isbelieved to originatefrom the lymphat-ics. Infiltration ofbronchioles leads tofocal emphysema

contralateral lung is involved preventingattempts at curative surgery. Chemo-therapy is of limited benefit. The dis-tressing symptoms of cough and breath-lessness need palliation.

Bronchial carcinoidThis is the commonest benign lungtumour. Embryologically it is derivedfrom fore-gut neuroendocrine cells. Itvery rarely presents as the carcinoid syn-drome of flushing and diarrhoea (in con-trast to mid gut carcinoid tumours withhepatic metastases). Biologically, there isa spectrum of behaviours.

The ‘typical’ carcinoid tumours arevascular endobronchial polypoid tumoursthat present usually in young women aseither recurrent haemoptysis or recurrentinfections with radiological infiltrates

59

Metastatic spread and the lung• The lung and pleura are common sites for metastatic

tumour deposition.

METASTATIC SPREAD AND THE LUNG

Fig. 3 Interstitial lymphatic spread: chest X-ray.

Fig. 6 Alveolar shadowing of bronchioalveolar cell carcinoma.

Fig. 4 Endobronchial deposit. This lady presented with haempotysis and anormal chest radiograph. Biopsy confirmed mucin-secreting adenocarcinoma,histologically similar to colonic cancer removed 4 years previously.

Haematogenous spreadLarge deposits (e.g. fromrenal, melanoma)Miliary small deposits(e.g. from thyroidcarcinoma)

Pleural deposits(often with fluid)• adenocarcinoma• breast• ovary• gut• lung

Endobronchialdeposits• colon• breast

Lymphangiticspread

Fig. 5 Metastatic spread to the lungs – common primary sites.

and air trapping. Veno-occlusion andlymphatic involvement contributes to theclinical picture. It occurs almost exclu-sively in women of reproductive age, andgrowth seems dependent on oestrogenhormones.

Presentation is in early to middleadult life with breathlessness and airflowlimitation. Frequent complications includehaemoptysis, pneumothorax or chylouseffusions. The chest radiograph willshow a reticular pattern to the lungparenchyma. High-resolution CT lungscanning will demonstrate thin-walledcystic airspaces. Treatment is supportivewith progesterone until a menopause.

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Intravascular thrombi originate in systemic veins, usually in the deep veinsof the lower limb, and migrate into thepulmonary circulation.They are rela-tively frequent within hospitalisedpatients, can be difficult to diagnose andyet fatal. Several studies have demon-strated prevalences in a hospitalised pop-ulation of venous clot ranging from lessthan 10% when associated with minormedical illness to exceeding 70% follow-ing surgery for traumatic hip fractures.Embolism into the pulmonary circulationmay cause 10% of all hospital deaths.

MECHANISMS

Intravascular thrombus formation usuallystarts in the deep venous system of thecalf. This is called a ‘deep vein thrombo-sis’ (DVT). The mechanisms that preventthe formation and propagation of intra-vascular thrombus fail as a result of:

• Abnormal or damaged vascularendothelium, especially important forarterial thrombosis and within grafts,less of a factor in calf veins except inrecurrent venous thrombosis.

• Blood stasis or pooling, usuallyresulting from immobility.Immobility is the most prevalentpredisposing factor, closely followedby the cause of the immobility.Trauma, following surgery, and manymedical illnesses are associated withan acute inflammatory response thatleads to the following.

• Imbalance between the blood’s pro-coagulant and thrombolyticproperties that favours coagulation.Conditions include malignancy,particularly disseminatedadenocarcinomas, therapy withoestrogens either as contraceptives orhormone replacement, or theantiphospholipid antibody syndrome.Moreover rare inherited deficienciesof particular fibrinolytic proteins canfavour a procoagulant tendency.

DEEP CALF VEIN THROMBOSIS

Often such clot is clinically silent thoughlocalised calf discomfort, swelling andwarmth may occur. Such features are notdiagnostic but are more likely when clotpropogates proximally into the thighveins. It is this proximal extension that ismost at risk of embolising. The presenceof clot should be actively confirmed orexcluded by radiological investigation.

The two most available imaging investi-gations are:

• Lower limb ascending venography.This is considered to be the goldstandard investigation. The techniqueuses intravenous contrast toradiologically outline the deepvenous system of the legs from calfextending proximally into femoraland iliac vessels. Thrombus isdemonstrated as consistent fillingdefects within the outlined vessels.The technique involves radiationexposure and the slight risk of reactionto the radio-opaque contrast used.

• Doppler ultrasound examination ofthe veins.This utilises thedemonstration of a Doppler signal byflowing blood with the deep veins.The absence of a spontaneous flowsignal in non-compressible veins canbe taken as evidence of occlusivethrombus. Although it is lesssensitive than venography in imagingthe calf veins, it is as good frompopliteal to iliac vessels. Being freeof ionising radiation, suchexaminations can readily be repeatedif clinical circumstances require.

Deep venous clot proximal to the calfis treated with anticoagulant therapy toprevent further extension, traditionallyheparin alone or followed by warfarin.During such therapy the existing clot willbe lysed by endogenous systems. Thisrecanalisation is at the expense of losingthe competence of venous valves. Thelong term sequelae of such venousincompetence includes the ‘post-phlebitic’ leg with chronic swelling, painand ulceration. There is some evidencethat treatment by thrombolysis (ratherthan anticoagulant therapy) and long-term wearing of support hosiery mayreduce this complication.

PULMONARY EMBOLI (PE)

Proximal leg vein thrombus may breakoff and travel through the right heartwith the potential there for outflowobstruction, before lodging and occlud-ing part of the pulmonary vascular bed.The consequences of such acute emboli-sation are:

• Breathlessness due to the loss ofpulmonary vascular bed but withoutthe degree of localised circulatorycompromise that results in lung

infarction. There may be few clinicalsigns.

• Pulmonary infarction syndrome withsudden onset pleurisy and coughoften productive of blood with unduebreathlessness. Clinical signs mayinclude localised crackles, pleuralfluid and occasionally a pleural rub.Chest radiographs may show thedevelopment of intrapulmonarypleural-based shadowing with pleural fluid.

• Sudden collapse as a result ofsubstantial clot causing obstruction tothe outflow tract of the right ventricleor a major pulmonary artery. Thesymptoms may not be immediatelyrecognised for what they represent:acute central chest pain,breathlessness and circulatorycollapse, systemic hypotension butwith distended neck veins: a ‘rightheart syndrome’. Death may ensue.Substantial loss of the pulmonaryvascular bed occurs but thecardiovascular effects are more thanthe mere consequences of vascularbed loss. Right ventricular and evenleft ventricular dysfunction with therelease of vasoactive inflammatorymediators as a result of theintravascular clot is as important. Incontrast, closing the vascular supplyto one lung surgically, or by vesselocclusion with inert material, causesonly transient haemodynamic effects.

Repeated embolisation of clot to thepulmonary circulation over days toweeks can lead to the syndrome of ‘corpulmonale’ with breathlessness, hypoxia,right heart strain and fluid retention.

Clinical featuresThe clinical features of pulmonaryembolism are non-specific. There arefew other potentially lethal conditions forwhich our clinical diagnostic accuracy isso poor. In an acutely ill or post-operativepatient there are a number of other diag-nostic possibilities, including pneumo-nia. The entire clinical picture includingan assessment of risk supplemented bychest radiography, electrocardiographyand arterial blood gases can provide afeel for the likelihood of a pulmonaryembolus or the possibility of an alternatediagnosis. Further investigation has to beperformed to confirm or refute the diag-nosis of pulmonary emboli because ofthe potential lethality and the therapeutic

PULMONARY THROMBOEMBOLI

RESPIRATORY DISEASE ⟩ PULMONARY VASCULAR DISEASE60

selby pp60-63 18/4/02 7:24 AM Page 60

implications. Further investigation can be directed

to either confirming the presence of deepleg vein clot from which embolisationwas possible, or confirming pulmonaryembolisation.

The pulmonary arterial circulationcan be imaged at pulmonary angiographywhere clot can be visualised as fillingdefects (Fig. 1). This is the probably thedefinitive investigation but is not alwaysavailable. Isotope lung scanning providesa simpler means to image lung perfusion(Fig. 2) but interpretation of such scans isnot always easy and over-interpretationis a risk. About 60% of lung scans areunhelpful in either confirming or refutingpulmonary embolism as the diagnosis. Insuch cases additional imaging is requiredwhich may include leg vein imaging.Echocardiography is often readily avail-able, can demonstrate acute right heartstrain with pulmonary hypertension andhelps to exclude other causes of an acuteright heart syndrome. Alternative tech-niques include helical CT scanning withcontrast (p. 77) and magnetic resonanceimaging; both techniques may be usefulin demonstrating large pulmonary vesselclot.

ManagementAnticoagulant therapy is the mainstay oftreatment. It should be commenced oncethe diagnosis is suspected, as long asthere are no contraindications to suchtherapy. Once anticoagulant therapy iscommenced, mortality falls to less than10%. Unfortunately, only 10% of deathsattributed to PE received any such treat-ment prior to death.

Anticoagulant therapy should be commenced as heparin, and warfarin isthen started. Heparin can be discontinuedonce the effect of warfarin is therapeutic.Heparin alone is used in the later stages ofpregnancy, but with the added risks ofimmune thrombocytopenia and of osteo-porosis with such long-term therapy.

Recurrent embolisation that continues

from leg vein clot once anticoagulation isestablished requires consideration of aninferior vena caval interruption device.This is usually a ‘caval filter’, anumbrella net that is placed percuta-neously and acts truly as a filter.

The role of thrombolysis in acute massive PE associated with majorhaemodynamic upset is still controversialbut may be lifesaving.

The most efficient way to preventboth fatal and non-fatal pulmonaryemboli and DVT is aggressive prophy-laxis in at-risk hospital patients. This canbe achieved using mechanical techniquesincluding early mobilisation and legcompression devices. Subcutaneousheparin as the low molecular weightheparins now available are effective andsimple to use. No technique is com-pletely reliable in preventing pulmonaryemboli.

Miscellaneous sources of thromboticpulmonary emboliThese are summarised in Figure 3. Thereare rare sources of pulmonary embolithat should be considered in any of thepulmonary thromboembolism syndromeswhen leg vein clot is demonstrablyabsent. These include:

• Clot from the right heart includingmural thrombus in dilated right

Pulmonary thromboemboli

• Pulmonary embolisation is potentially lethal and often complicates hospitalisation and major illness.

• It can be difficult to diagnose, with patients receiving risky therapy when they have not suffered the condition and other patients going untreated for an undiagnosed life-threatening condition.

• Clinical assessment alone is insufficient for diagnosis or upon which to base long-term treatment decisions. Radiological imaging is essential to confirm the diagnosis.

• Preventative therapy, whether physical or pharmacological, is the most cost-effective.

61

Case history 26

A 30-year-old female on the oralcontraceptive pill with a history ofpoorly controlled asthma presentswith rapid onset severe breath-lessness and pleurisy. A chest radiograph is normal. Havingstarted treatment for pulmonaryemboli, how could you confirmyour suspicions?

PULMONARY THROMBOEMBOLI

Fig. 1 Pulmonary artery clot demonstrated bycontrast angiogram.

Fig. 2 Isotope perfusion lung scan illustratingimpaired delivery to left upper and right lowerlung regions. These perfusion defects representvascular bed obstruction from emboli (chestradiograph normal).

Fig. 3 Miscellaneous sources of thromboticpulmonary emboli.

Tumouralong

vein

Thrombus, ofteninfected on centralvenous catheter

Right axial myxoma

Right ventricularmural thrombus,following infarctionor when dilated andpoorly functioning

Amyloid kidney,renal veinthrombosis

Renal carcinomawith tumourextension along orin situ thrombosis

Pelvic vein clot

ventricles.

• Embolisation from the renal veinscan occur. The material is eithertumour spreading directly along therenal vein or renal vein thrombosisespecially in amyloidosis.

• Right heart myxomas areexceptionally rare.

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