6. Bronhoscopia in Dg Si Trat Cancerului Pulm

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Bronchoscopic techniques indiagnosis and staging of lungcancer

SummaryTechnologic advances in bronchoscopy continue to improve our ability to performminimally invasive, accurate evaluations of the tracheobronchial tree and to perform anever-increasing array of diagnostic, therapeutic, and palliative interventions. The roleof both old and new diagnostic bronchoscopy will continue to evolve as furtherimprovements are made in bronchoscopes, accessory equipment, and imaging tech-nologies. The major challenge in the adoption of the many new bronchoscopic tech-niques into routine clinical practice is the need for well-designed studies to delineate theappropriate use of these interventions and to better define their limitations.

IntroductionThe first bronchoscopy was performed in 1887

by Gustav Killian of Freiburg, Germany [1].During the early years of the development

of bronchoscopy, the indications for the proce-dure were primarily therapeutic: removal offoreign bodies and dilation of strictures fromtuberculosis and diphtheria. In the early partof the 20th century, Chevalier Jackson, thefather of American Broncho-EsophagologyAssociation, further advanced bronchoscopictechniques and designed modern rigid bronch-oscopies [2]. Again, the primary indicationwas often therapeutic.

Fibreoptic bronchoscopy (FOB) was devel-oped in the late 1960s by S. Ikeda [3] and hasbecome the mainstay investigation in the eva-luation ofpatientssuspected of lung cancer. It isemployed mainly as a diagnostic tool providingtissue to determine the histological type oftumour. Bronchoscopy also has a role in diseasestaging and an extended role in deliveringtherapeutic modalities. FOB is convenient toperform, safe and well tolerated by the patient.

The requirement of minimal sedationmakes it acceptable as an outpatient proce-dure, thus it has almost completely replaced

rigid bronchoscopy in the initial assessment.The development of video bronchoscopes hasthe added advantage of facilitating teaching

and rendering the procedure more interestingfor other observers in the bronchoscopy suite.

The flexibility of the bronchoscope allowsthe operator to inspect the majority of fourth-order and often up to sixth-order bronchi. Inaddition, the operator may directly assessmucosal details, such as colour and vascularity.Relative contraindications to the procedure arefew and include: hypoxaemia refractory tosupplemental oxygen (O2), intractable bleed-ing diathesis, severe pulmonary hypertension,cardiovascular instability and acute hypercap-

nia [4].FOB is safe with a complication rate of0.12% and a mortality rate of 0.04% [5]. Thedangers of haemorrhage and pneumothoraxrelate to the biopsy procedure used and willbe discussed later. In all patients, thebronchoscope causes a temporary increase inairflow obstruction, which may result inhypercapnia [6]. Inappropriate sedation withbenzodiazepines or opiates will increase thelikelihood of respiratory complications andhigh-risk patients should be identified by priormeasurement of arterial blood gases [57].

HERMES syllabus link: module

D.2, B.2

F.J.F. Herth

CorrespondenceF.J.F. HerthDepartment Pneumology andCritical Care Medicine

Thoraxklinik at the University ofHeidelberg

Amalienstrae 5D-69126 Heidelberg

GermanyFelix.Herth@

thoraxklinik-heidelberg.de

Competing interests

None declared.

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Supplemental O2 should be provided and pa-tients should be monitored throughout withpulse oximetry. Cardiac monitoring should beused for those patients with a history ofischaemic heart disease and resuscitation equip-ment immediately available.

Although FOB has largely replaced rigidbronchoscopy in the initial assessment of thepatient, the rigid scope has advantages incertain situations [8]. As mentioned, it mayprovide more accurate information regarding theendobronchial location of a tumour prior toresection.

Additionally, manipulation of the scopeallows assessment of the mobility of theproximal airways providing an indirect evalua-tion of mediastinal nodal involvement. Airwayobstruction is less and thus the rigid scope may

be preferable in exploring patients with trachealnarrowing in whom the flexible scope mayproduce critical airway narrowing. It providessuperior suction, facilitating the assessment andbiopsy of potentially haemorrhagic lesions andthe debulking of large tumours [810]. Inaddition, many physicians are now relearningthe technique to facilitate endobronchial lasertherapy and stenting procedures [11].

The diagnostic yield offibreopticbronchoscopyThe expected diagnostic yield from FOB dependson the location and distribution of the tumour.Central endobronchial lesions yield the highestdiagnostic return (.90%), whilst small periph-eral lesions often prove more elusive unless moredemanding and time-consuming techniques areused. The question of which combination ofcytological and histological procedures providesthe optimum diagnostic yield has not beenconclusively answered but probably depends on

the expertise available in any individual centre.The routine techniques include bronchial wash-ings, brushings and biopsies but these may beaugmented by the use of transbronchial needleaspiration (TBNA) and bronchoalveolar lavage(BAL) [12].

More than 70% of lung carcinomas arevisible to the FOB and although the yield isdependent on operator experience, a high levelof diagnostic accuracy can be achieved by takingbetween three and five biopsy specimens and acombination of brushing, biopsy and bronchialwashes can expect to establish a diagnosis in

.60% of cases [6, 7, 13, 14]. When the tumouris visible but is intramural rather than endobron-chial in distribution, the diagnostic yield falls to55% and is reduced further when the tumourlies beyond the bronchoscopists vision [6, 7, 12].

The main role of BAL in patients with lung

cancer is the diagnosis of opportunistic infectionsin patients undergoing chemotherapy. However,BAL may have an extended role in the diagnosisof malignancy itself. A high diagnostic yield hasbeen shown in the detection of pulmonaryhaematological malignancies, primary bronchoal-veolar cell carcinoma and metastatic adenocarci-noma of the breast [1517].

Information on the role of BAL in thediagnosis of primary lung cancer remains sparse.

Examination of BAL from 55 patients with aperipheral lung lesion demonstrated a diagnostic

yield of,

30% with no false-positive results andonly one instance of incorrect cell typing. Addi-tionally, in combination with bronchial washingand post-bronchoscopy sputum, BAL increasedthe yield to 56% [18]. Examination of BAL in162 patients with malignant lung infiltratesrevealed improved sensitivity in cases of bronch-oalveolar cell carcinoma (93%) and lymphangitiscarcinomatosa (83%). 45% of non-Hodgkinslymphoma was detected and immunocytochem-istry was of value in identification and classifica-tion [19].

BAL is safe; bleeding and pneumothorax areuncommon and the fever and transient loss oflung function reported are rarely serious andthere is no requirement for fluoroscopy. Further-more, the diagnostic yield is high in diseasesother than cancer, such as pulmonary tubercu-losis. Advances in cell and molecular biologymay complement the technique of BAL toimprove the rate of tumour diagnosis in periph-eral lesions (particularly adenocarcinoma) andmay also provide a useful tool to explore themolecular mechanisms governing the genesis oflung cancer [2022].

Visible endobronchiallesionsCentral tumours can present as exophytic masslesions, with partial or total occlusion of thebronchial lumen, as peribronchial tumours withextrinsic compression of the airway, or withsubmucosal infiltration of tumour. The changeswith peribronchial tumours or with submucosalinfiltration are often subtly, the airways shouldbe examined closely for characteristic changes,


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such as erythema, loss of bronchial markings andnodularity of the mucosal surface. Central lesionsare usually sampled with a combination of bron-chial washes, bronchial brushings and endobron-chial biopsies. The yield of endobronchialbiopsies is highest for exophytic lesions, with a

diagnostic yield of,90% [2325]. Three to fourbiopsies are likely adequate in this situation.Attempts should be made to obtain the biopsiesfrom areas of the lesion that seem viable.

For submucosal lesions, TBNA can beperformed by inserting the needle into thesubmucosal plane at oblique angle, and inpatients with peribronchial disease and extrin-sic compression, the needle should be passedthrough the bronchial wall into the lesion[26, 27]. It is particularly frustrating whenapparently adequate biopsy specimens from

visible endobronchial disease fail to achieve adiagnosis. Reasons for this include thepresence of surface necrosis or the presenceof crush artefact (particularly common withsamples from small cell carcinoma). In thesecircumstances, TBNA may improve diagnosticyield [28, 29].

Regarding the T staging, FOB may allow theoperator to determine that the tumour is beyondresection. Pointers to inoperability include:paralysis of a vocal cord; tumour to the level ofthe right tracheobronchial junction or to within

2 cm of the left tracheobronchial junction; anddefinite carinal or tracheal involvement (fig. 1).

Peripheral lunglesionsPeripheral lesions are usually sampled with acombination of bronchial wash, brushes, trans-bronchial biopsy and TBNA. The diagnostic yieldof bronchoscopy for peripheral lesions dependson a number of factors, including lesion size, thedistance of the lesion from the hilum and on therelationship between the lesion and bronchus.The yield of bronchoscopy for lesions ,3 cmvaries from 1450% compared with a diagnosticyield of 4680% when the lesion is .3 cm[3032]. The presence of a bronchus sign onchest CT predicts a much higher yield ofbronchoscopy for peripheral lung lesions. Inthese cases, fluoroscopic guidance should beused to ensure proper positioning of the

diagnostic accessory (fig. 2).Fluoroscopy increases the diagnostic yield

from transbronchial biopsy (TBBX) in focal lunglesions but it is time consuming, requiresexperience and is not universally available.However, if the disease process is diffuse, suchas in lymphangitis carcinomatosa, yields aresimilar whether fluoroscopy is used or not [33].Indeed, Tbbx may be regarded as the procedureof choice for Iymphangitis carcinomatosa.Complications from TBBX include pneumothoraxand haemorrhage but these are generally lowand rarely serious.

In situations where bronchial biopsies cannotbe obtained, examination of bronchial washingsmay still yield useful information and oftenprovide complementary information [34, 35]. Itis often prudent to perform all types of samplingprocedure to maximize the yield [12].


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Figure 1

Fibreoptic bronchoscopic image showing a tumour that

is inoperable due to location.

Figure 2

Computed tomography image of a chest showing a

bronchus sign.


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Several studies have demonstrated thatTBNA may be used to obtain diagnostic tissuefrom peripheral lesions. Typical results report anincrease in the diagnostic yield from percent-age figures in the mid-30s up to the high-60s[12, 3638]. As with Tbbx, the size of the periph-

eral lesion appears to be important; although,this is not a feature of all studies. Optimumyields are provided by employing a combinationof diagnostic techniques. TBNA may representan alternative to TBBX when the airway isstenosed or externally compressed to such adegree that it is not possible to pass the TBBXforceps.

The need to workup and manage pulmon-ary nodules and masses is encountered withincreasing frequency in chest medicine. Inpatients with such nodules, the diagnostic

procedure is usually performed as a TBBXunder fluoroscopic guidance. The commonlyperformed procedure, endoscopic transbron-chial biopsy, is associated with a low yield incoin lesions ,3 cm in size or fluoroscopicallyinvisible lesion problems. The yield dependsgreatly on the size and location of theabnormality [39, 40] and generally on theability to visualise the lesion fluoroscopically.Nodules that are too small to be visualised byconventional fluoroscopy during the procedurepose a particular problem and usually requirefurther, often surgical, biopsy procedures.

If issues of diagnostic yield could beresolved, flexible bronchoscopy would representa very interesting part in the workup andmanagement of lung lesions. What is needed,therefore, are new methods for navigation andlocalisation, independent of visualisation byfluoroscopy, but still dependent on the technicalskills of the bronchoscopist. Promising newtechnologies are electromagnetic navigationand endobronchial ultrasound.

Electromagnetic navigationThe electromagnetic navigation system is alocalisation device that assists in placingendobronchial accessories (e.g., forceps, brushand needle) in the desired areas of the lung.

The system uses low-frequency electromag-netic waves, which are emitted from anelectromagnetic board placed under thebronchoscopy table mattress. A 1-mm diameter,8-mm-long sensor probe mounted on the tip of aflexible metal cable constitutes the mainassembly of the device (locatable guide). Oncethe probe is placed within the electromagnetic

field, its position in the X, Y and Z planes, as wellas its orientation (roll, pitch and yaw move-ments), are captured by the electromagneticnavigation system. This information is thendisplayed on a monitor in real time. Thelocatable guide also has an added feature that

allows its distal section to be steered 360u. Thefully retractable probe is incorporated into aflexible catheter (serving as an extended workingchannel), which, once placed in the desiredlocation, creates an easy access for broncho-scopic accessories. The computer software andmonitor allow the bronchoscopist to view thereconstructed three-dimensional computer tomo-graphy (CT) scans of the objects anatomy incoronal, sagittal and axial views together withsuperimposed graphic information depicting theposition of the sensor probe.

There are still some major limitations tothe technique. For planning, a CT scan isnecessary with a special protocol (1-mm cutsand tight overlay). For the planning of theprocedure, the use of the electromagneticnavigation bronchoscopy (ENB) software isrequired. The planning can be done even onthe system or on a special dedicated laptopbefore the procedure; the planning needssome time, up to 10 min in trained colleagues.The whole procedure time is prolongedcompared with a traditional diagnosticbronchoscopy with fluoroscopy; but compared

with the technique we have at the moment forlesions of this size, CT-guided punctures, thetime is equivalent. Last but not least, thelocatable guide is single use and costsUS$5001,000, depending on the market.The reimbursements are also dependent onthe local systems and vary US$01,000.SCHWARZ et al . [41] performed a trial todetermine the practicality, accuracy and safetyof real-time electromagnetic navigation inlocating artificially created peripheral lunglesions in a swine model. No adverse effects,

such as pneumothorax or internal bleeding,were encountered in any animal in this study.They concluded that real-time electromagneticpositioning technology, coupled with pre-viously acquired CT scans, is an accuratetechnology that can augment standardbronchoscopy to assist in reaching peripherallung lesions and performing biopsies.

Based on the results of that study, BECKERet al. [42] performed a pilot study in humans.They examined the utility of the system in 30consecutive patients presenting for endoscopicevaluation of lung nodules and masses. The


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lesion size in this population varied 12106 mmbut was specifically not controlled for in thisearly trial. Evaluation was possible in 29 patientsand, in 20 patients, a definitive diagnosis wasestablished, with no complications related to thenavigation device.

In an uncontrolled study, again SCHWARZet al. [43] confirmed that the procedure wassafe and added only an average of 15 min tothe time of a conventional bronchoscopy. Succes-sful diagnostic biopsies were obtained in 69% ofpatients. A follow-up study of 60 patients [44],published in 2006, successfully reached thetarget lesion in 100% of cases. Bronchoscopywith electromagnetic navigation diagnosed80.3% of the lesions, 74% of the peripherallesions and 100% of the lymph nodes. Of thelesions, 57% were ,2 cm in size. Diagnostic

yield did not differ significantly based on the sizeof the lesion. The accuracy of ENB navigationhas been proven in animal studies and againstfluoroscopically verified reference points inhumans [43, 44]. Nevertheless, all precedingdiagnostic studies utilising ENB also usedfluoroscopy to guide biopsies. The role of ENBas a standalone technology is still unproven andconcerns remain that biopsy instruments maydislodge an accurately positioned extendedworking channel (EWC) when replacing thesensor probe.

EBERHARDTet al. [45] examined the yield of

ENB without fluoroscopy in the diagnosis ofperipheral lung lesions and solitary pulmonarynodules. 92 peripheral lung lesions werebiopsied in the 89 subjects. The diagnostic yieldof ENB was 67%, which was independent oflesion size. The mean navigation error was96 mm (range 131 mm). When analysed bylobar distribution, there was a trend towards ahigher ENB yield in diagnosing lesions in theright middle lobe (88%). The study concludedthat ENB could be used as a standalonebronchoscopic technique without compromising

diagnostic yield or increasing pneumothorax risk.This may result in sizable time saving and avoidsradiation exposure.

MAKRISet al. [46] confirmed these results. In40 patients all target lesions but one werereached and the overall diagnostic yield was62.5% (25 out of 40). Also, the French groupsummarised that electromagnetic navigation-guided bronchoscopy has the potential toimprove the diagnostic yield of transbronchialbiopsies without further fluoroscopic guidanceand may be useful in early diagnosis of lungcancer, particularly in non-operable patients.

Endobronchial ultrasoundAt the moment, two different systems areavailable. The linear endobronchial ultrasound(EBUS) bronchoscope, which incorporates theultrasound transducer at its distal end, utilises afixed array of transducers aligned in a curvilinear

pattern.Owing to the size of the scope, the system is

usable only in the central airways. For theperipheral lung the radial EBUS must be used.The radial EBUS system consists of a mechanicalradial miniprobe.

Two types of miniprobe are available, onewith a notch at the tip for a water-fillable ballooncatheter, one without a notch. Particularly withthe notch type, ultrasonography can be per-formed using the balloon method, that is, theballoon is inflated at the distal end of the probe

after the probe has been inserted into theinstrument channel.

The balloon method makes easy delineationof ultrasound images possible, even at siteswhere it is hard to retain defecated water. Thelimitation is the size: with the balloon sheath, anendoscope o2.8 mm diameter channel has tobe used. The notchless probe is smaller (1.7 mm)and can also be used in smaller scopes.

The 20-MHz frequency is commonly used,although 12- and 30-MHz probes are alsoavailable. For use in the peripheral lung, most

commonly the probe is placed through a guidesheath in the working channel of the broncho-scope. After localisation of the lesion (fig. 3), thebronchoscope will be kept in place at the nearestvisible subsegmental carina and the miniproberemoved. Through the guide sheath, the forceps


D.2, B.2Figure 3

Endobronchial ultrasound showing a lesion.




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the diagnosis of endobronchial and peripherallesions and the ability of TBNA to provide adiagnosis even in the absence of endobronchialdisease, in a nonsurgical fashion, confirmed itsusefulness to bronchoscopists [6264].

Operators have reported the use of 21- and

22-gauge cytology needles and 19-gaugehistology needles [65]. Further samples areprovided by rinsing the needle with a smallvolume of normal saline and collecting theflush solution for analysis. Although TBNA isnot widely used, it appears to improve thediagnostic yield when sampling from visibleendobronchial, submucosal and peripherallesions. Additionally the technique may detectmediastinal disease potentially allowing theoperator to diagnose and stage a lung tumourin one procedure carried out under local

anaesthetic.TBNA may be used to sample Iymph nodesthat lie immediately adjacent to the trachea andmajor bronchi. Care must be taken to performTBNA prior to inspection of the distal airwaysand other sampling procedures as contaminationwith exfoliated malignant cells are a recognisedcause of false-positive results. Studies havereported sensitivity rates of 4383% and positivepredictive values of 89100% [6671]. Use ofa 19-gauge needle provides greater sensitivitythan a 22-gauge needle but a combinationof samples provides the best yields [65, 72].

Although the positive-predictive value is high(often 100%) the negative-predictive value islow and does not obviate the requirement forfurther surgical staging [6272].

A potential limitation of mediastinal lymphnode staging with TBNA is that the operator isblind. The technique may be combined with thatof endobronchial ultrasound by the miniprobes[73, 74].

The numerous papers on TBNA performedin the last few years confirm the safety of theprocedure. No cases of mortality related to

TBNA have been described. The rare complica-tions reported are: pneumothorax [75], pneu-momediastinum [76], haemomediastinum [77],bacteraemia [78] and pericarditis [79]. None ofthese complications determined clinical majorconsequences.

One of the major complications of TBNA isthe possible severe damage to the workingchannel of the scope [64]. This is more frequentwith nonretractable needle (that should nolonger be available in the market) and can beavoided if the operator takes care in introdu-cing and extracting the needle from the

bronchoscope with the tip completely retractedin the sheath.

Endo-oesophageal ultrasoundwith fine needle aspiration

Endo-oesophageal ultrasound with fine needleaspiration (EUS-FNA) is a relatively new method,first described in 1991 [80]. Since then, severalstudies have been published and it has beendemonstrated that generally all lesions outlinedby EUS may be punctured, and even smalllesions down to the size of 5 mm may bediagnosed [81].

EUS-FNA is performed with the aid ofoesophagoscopy and a biopsy needle is passedthrough the working channel of the endoscope,through the oesophageal wall and guidedultrasonographically toward the lesion of interest

in the mediastinum. The procedure is performedunder local anaesthetic and conscious sedation.This method gives an excellent overview ofmediastinal structures, including a good accessto the para-oesophageal space, the aortico-pulmonary window, the sub-carinal region andthe region around the left atrium (level 4, 5 and7) [8284] and then EUS has the advantage ofbeing noninvasive, safe and cost effective [85].However, an area anterior to the air-filled tracheacannot be visualised.

The procedure can be per formed under i.v.

sedation using midazolam or propofol [82]. Theechoendoscope is initially introduced up to thelevel of celiac axis and gradually withdrawnupwards for a detailed mediastinal imaging.Since the ultrasound waves are emitted parallelto the long axis of the endoscope, the entireneedle can be visualised approaching a targetin the sector-shaped sound field. Pulse-waveDoppler ultrasonography imaging is performed,whenever vascular structures were supposed inthe pathway of the needle or adjacent to it, tocorrect the target line if necessary [84]. The

needle is advanced through the wall of theoesophagus and guided into the target lesion.The central stylet is removed, and a special10-mL syringe attached to the hub of the needleto applysuction astheneedleis moved back andforth within the mass. The suction is releasedslowly and the needle assembly removed out ofthe biopsy channel. One to two needle passeswere made to obtain adequate tissue [86, 87].

Visual assessment of mediastinal lymphnodes by EUS gave for various observers sensi-tivities of 0.540.75, specificities of 0.710.98,positive-predictive values of 0.460.77, and


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93%. As in all other trials, no complicationsoccurred.

A DanishGerman group [102] additionallyexamined the accuracy of EBUS-TBNA insampling nodes ,1 cm in diameter. Among100 patients, 119 lymph nodes with a size of

410 mm were detected and sampled.Malignancy was detected in 19 patients butmissed in two others; all diagnoses wereconfirmed by surgical findings. The meandiameter of the punctured lymph nodes was8.1 mm. The sensitivity of EBUS-TBNA fordetecting malignancy was 92.3 %; the specificitywas 100%; and the negative-predictive valuewas 96.3 %. Again, no complications occurred.They summarised that EBUS-TBNA can sampleeven small mediastinal nodes, therefore avoidingunnecessary surgical exploration in 1 out of 5

patients who have no CT evidence of mediastinaldisease. Potentially operable patients withclinically nonmetastatic NSCLC may benefit frompresurgical EBUS-TBNA biopsies and staging. Astudy comparing EBUS-TBNA, CT and PET forlymph node staging of lung cancer showed ahigh yield for EBUS-TBNA [103]. Altogether, 102potentially operable patients with proven(n596) or radiologically suspected (n56) lungcancer were included in the study. CT, PET andEBUS-TBNA were performed prior to surgery forthe evaluation of mediastinal and hilar lymphnode metastasis. The sensitivities of CT, PET and

EBUS-TBNA for the correct diagnosis of medias-tinal and hilar lymph node staging were 76.9,80.0 and 92.3%, respectively; the specificitieswere 55.3, 70.1 and 100%, respectively; and thediagnostic accuracies were 60.8, 72.5 and98.0%, respectively. EBUS-TBNA was proven tohave high sensitivity and specificity, comparedwith CT or PET, for mediastinal staging inpatients with potentially resectable lung cancer.

Restaging of the mediastinum is anotherarea of growing interest for the treatmentstrategy of lung cancer. In cases of advanced

lymph node stage lung cancer, inductionchemotherapy prior to surgical resection is anoption. Mediastinoscopy is considered the goldstandard for staging the mediastinum. However,re-mediastinoscopy can be technically difficultand is therefore not commonly performed. Theability to perform multiple, repeat biopsies usingEBUS-TBNA allows restaging of the mediastinumafter the introduction of chemotherapy.

A group of 124 consecutive patients withtissue-proven IIIA-N2 disease who were treatedwith induction chemotherapy underwent medi-astinal restaging by EBUS-TBNA. The sensitivity,

specificity, positive predictive value, negativepredictive value, and diagnostic accuracy ofEBUS-TBNA for mediastinal restaging followinginduction chemotherapy were 76, 100, 100, 20and 77%, respectively. EBUSTBNA is an accu-rate, minimally invasive test for mediastinal

restaging of patients with NSCLC. However,because of the low negative-predictive value,tumour-negative findings should be confirmed bysurgical staging [104].

EBUS-TBNA can be also used for thediagnosis of intrapulmonary nodules as well asmediastinal and hilar lymph nodes. The limita-tion is the reach of EBUS-TBNA, which dependson the size of the bronchus. Usually the EBUS-TBNA can be inserted as far as the lobarbronchus. Lung tumours located adjacent to theairway within reach of EBUS-TBNA can be

diagnosed with EBUS-TBNA. TORNOUYet al. [105]have reported their experience is this indication.In 60 patients, who have had a nondiagnosticbronchoscopy before, they were able to establishthe defintive diagnosis in 77% without anycomplication.

Complications related to the procedure aresimilar to those of conventional TBNA, includingbleeding from major vessels, pneumomediasti-num, mediastinitis, pneumothorax, bronchospamand laryngospasm. Complications related toEBUS-TBNA have not been observed and todate there are no major complications reportedin the literature. Although EBUS has enabled thebronchoscopist to see beyond the airway, onemust be aware of the possible complicationsrelated to the procedure [106, 107].

Rapid on-site evaluationRapid on-site evaluation (ROSE) is comparablewith the intra-operative frozen-section examina-tion. The technique requires the cytopathologistand the pathology technician to process andinterpret the stained wet film of the aspirate

immediately and report the result to thebronchoscopist. For all needle techniques advan-tages are to resume. Several studies have shownthat ROSE reduces the incidence of inadequatespecimens, an important cause of nondiagnosticTBNA aspirates [108111].

DAVENPORT [112] studied the value of ROSEin 73 aspirates and compared the results with134 specimens processed routinely. The aspirateswere obtained from the mediastinal lymphnodes and the peripheral lung nodules. WithROSE, the proportion of aspirates showingmalignant cells increased from 31% to 56%.


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The proportion of the inadequate negativespecimens dropped from 56% to 18%. Thenegative aspirate with ROSE had a highernegative-predictive value than that of routinelyprepared specimens. In a recent prospectivestudy, DIETTEet al. [113] evaluated transbronchial

needle aspirates with ROSE in 81 of 204 cases.The overall diagnostic yield was 81% whenROSE was used compared with a 50% yieldwhen specimens were processed in the usualmanner. Multivariate analysis showed that ROSEwas an independent predictor of a positiveaspirate for malignant cells with an odds ratio of4.5. The mean number of needle attempts wasslightly greater with ROSE. The concordance

between the preliminary diagnosis made in thebronchoscopy suite and the final diagnosis wasreached after subsequent review of material inthe cytopathology laboratory was 87% indicat-ing that the onsite evaluation of needle aspirateis fairly accurate but not perfect.

Although ROSE seems to improve thediagnostic yield of TBNA, its cost-effectivenessremains unclear. Successful use of ROSE requiresservices of an expert cytopathologist. Manypathologists do not favour ROSE because of theextra time and effort involved. The reimburse-ment from a third-party payer for these services ishighly variable. Presently, the decision to useROSE should be made on a case-by-case basis.

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