ebus

Research ArticleUtility of Endobronchial Ultrasound-GuidedTransbronchial Needle Aspiration in Diagnosis ofIntrathoracic Lymphadenopathy in Patients with HumanImmunodeficiency Virus Infection

Audrey Yan Yi Han, Aik Hau Tan, and Mariko Siyue Koh

Department of Respiratory and Critical Care Medicine, Singapore General Hospital, 20 College Road, Academia, Singapore 169856

Correspondence should be addressed to Aik Hau Tan; [email protected]

Received 25 June 2014; Revised 18 September 2014; Accepted 27 September 2014

Academic Editor: Andrea Zanini

Copyright © 2015 Audrey Yan Yi Han et al. This is an open access article distributed under the Creative Commons AttributionLicense, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properlycited.

Objective. Intrathoracic lymphadenopathy (LAD) in patients with Human Immunodeficiency Virus (HIV) infection is common,with wide-ranging diagnoses, from benign to malignant causes. Endobronchial Ultrasound-guided Transbronchial NeedleAspiration (EBUS-TBNA) is a relatively new technology with established applications in lung cancer, sarcoidosis, and tuberculosis.We sought to find out whether the addition of EBUS-TBNA to the diagnostic algorithm for LAD in HIV patients will reduce theneed formediastinoscopy.Methods. Retrospective chart review of all EBUS-TBNAprocedures performed in our centre fromAugust2008 to December 2012. Results. 513 patients had EBUS-TBNA performed during this period. We identified nine HIV-infectedpatients who had LAD of unknown cause and underwent EBUS-TBNA. The procedure reduced the need for mediastinoscopy ineight patients (89%). Conclusions. Potential mediastinoscopies can be avoided by utilising EBUS-TBNA in HIV patients with LAD.

1. Introduction

Intrathoracic lymphadenopathy (LAD) is a challengingproblem in patients infected with Human ImmunodeficiencyVirus (HIV). Jasmer et al. demonstrated an incidence of35% based on routine computed tomography (CT) scan,performed for a cohort of 318 patients with HIV infection[1]. Diagnoses are extensive, ranging from commonerdiagnoses of Mycobacterial infections (tuberculous andnontuberculous) and malignancies (lymphoma, primarylung cancer, Kaposi’s sarcoma) to less common diagnosesof reactive lymphadenopathy in infection (bacterial, fungal,Pneumocystis jirovecii pneumonia previously known asPneumocystis carinii pneumonia) and nonspecific lymphoidhyperplasia [1, 2].

Conventionally, patients would undergo mediastino-scopy or open biopsy via thoracotomy, which incur highermorbidity and a risk of general anaesthesia as com-pared to bronchoscopic procedures [3]. Conventional Trans-bronchial Needle Aspiration (TBNA) via bronchoscopy was

an alternative method of diagnosis, but with a diagnostic rateof only 52% when performed in this group of patients [4].Endobronchial Ultrasound-guided Transbronchial NeedleAspiration (EBUS-TBNA) is a relatively new technologywhich uses real-time linear ultrasound imaging to guideintrathoracic lymph node and lungmass tissue sampling dur-ing bronchoscopy. Its utility in the diagnosis of lung cancer[5], sarcoidosis [6], and tuberculosis [7] has been proven;in particular, it has been shown to have significantly bettersensitivity and yield than conventional TBNA for lung cancerand sarcoidosis [5, 6]. Our aim was to find out if addition ofEBUS-TBNA into the diagnostic algorithm for LAD in HIVpatients will reduce the need for mediastinoscopy.

2. Methods

Retrospective chart review of all EBUS-TBNA proceduresperformed in our centre fromAugust 2008 to December 2012was carried out. Completeness of data was ensured with the

Hindawi Publishing CorporationBioMed Research InternationalVolume 2015, Article ID 257932, 5 pageshttp://dx.doi.org/10.1155/2015/257932

http://dx.doi.org/10.1155/2015/257932

2 BioMed Research International

Table1:Dem

ograph

ic,clin

ical,and

radiograph

icfin

ding

s.

Num

ber

Age/sex

Smoker

Timee

lapsed

since

HIV

diagno

sis/current

treatment

Presentin

gsymptom

s/duration

Find

ings

oncompu

ted

tomograph

yof

thorax/other

significantimagingresults

CD4

(cells/mm

3 )

Lymph

node

sampled

a

(size,mm)

Histolog

y/cytology

Microbiologicalresults

Treatm

ent/o

utcome

Needfor

mediastino

scop

y(finald

iagn

osis)

173/M

Yes

5years/ART

Fever,coug

h,pu

rulent

sputum

/1week

Righth

ilarm

ass,

mediastinal

lymph

adenop

athy,bilateral

pulm

onaryno

dules

(<10mm)/multip

lehepatic

nodu

les,bilateraladrenal

nodu

larity,lytic

bone

lesio

ns

386

4R(30)

Smallcelllun

gcancer

TBcultu

refro

mTB

NA

negativ

eNot

treated/dem

ised

No

(smallcelllun

gcancer)

259/M

Yes

3mon

ths/un

treated

Hem

optysis/2

weeks

Mediastinaland

bilateral

axillarylymph

adenop

athy,

fibrobu

llous

diseaseinbo

thup

perlob

es

433

4R(6)

4L(12)

Bloo

dTB

cultu

refro

mTB

NA

negativ

eBA

Lcultu

resn

egative

Surveillance

No

(non

specific)

339/F

No

13years/d

efaulted

treatment3

years

Fever,weightloss/1

week

Mediastinaland

right

hilar

lymph

adenop

athy,2

nonspecific

pulm

onary

nodu

les(<10mm)

24R

(20)

Lymph

ocytes

TBcultu

refro

mTB

NA:

MAC

Bacterialand

fung

alcultu

resfrom

TBNA

negativ

e

Treatedfor

dissem

inated

MAC

/resolved

No

(diss

eminated

MAC

)

441/M

Yes

New

diagno

sis/untreated

Fever,coug

h,pu

rulent

sputum

,weightloss/2weeks

Necrotic

lefthilarm

ass,

mediastinal

lymph

adenop

athy,left

lower

lobe

nodu

les

127

7(30)

Lymph

ocytes

(mediastino

scop

y:necrotising

granulom

atou

sinflammation)

TBcultu

refro

mTB

NA

negativ

eBA

Lcultu

res:MTC

Mediastino

scop

ycultu

res:MTC

Treatedfor

MTC

/resolved

Yes

(TB)

540

/MNo

8mon

ths/ART

Cou

gh,n

onpu

rulent

sputum

/1mon

th

Necrotic

mediastinaland

right

hilar

lymph

adenop

athy,patchy

consolidationand

tree-in-bud

nodu

lesinrig

htlung

/necrotic

retro

periton

eal

lymph

adenop

athy

102

4R(30)

Necrotic

tissue

Acid

fastbacilli

present

TBcultu

refro

mTB

NA

negativ

eBA

Lcultu

resn

egative

Cervicallym

phno

decultu

re:M

AC

Treatedfor

dissem

inated

MAC

/resolved

No

(diss

eminated

MAC

)

BioMed Research International 3

Table1:Con

tinued.

Num

ber

Age/sex

Smoker

Timee

lapsed

since

HIV

diagno

sis/current

treatment

Presentin

gsymptom

s/duration

Find

ings

oncompu

ted

tomograph

yof

thorax/other

significantimagingresults

CD4

(cells/mm

3 )

Lymph

node

sampled

a

(size,mm)

Histolog

y/cytology

Microbiologicalresults

Treatm

ent/o

utcome

Needfor

mediastino

scop

y(finald

iagn

osis)

647/M

Yes

4years/ART

Anteriorc

hestwall

pain

andsw

ellin

g/1

week

Enlarged

precarinalno

de,

nolesio

nseen

inthe

anterio

rchestwall

114L

(15)

Necrotic

tissue

TBcultu

refro

mTB

NA

negativ

eSurveillance

No

(non

specific)

750/M

Yes

New

diagno

sis/untreated

Fever,appetite,and

weightloss/1m

onth

Necrotic

mediastinaland

right

hilar

lymph

adenop

athy/necrotic

intra-abdo

minal

lymph

adenop

athy

832R

(11)

Necrotic

tissue

TBcultu

refro

mTB

NA:

MTC

Fung

alcultu

refro

mTB

NAnegativ

e

Treatedfor

MTC

/resolved

No

(TB)

868/M

Yes

New

diagno

sis/untreated

Cou

gh,app

etite,and

weightloss/2weeks

Mediastinaland

bilateral

hilarlym

phadenop

athy,left

upperlob

emass/

intra-abdo

minal

lymph

adenop

athy

346

4L(12)

7(21)

10L(7)

Diffuselarge

B-cell

lymph

oma

TBcultu

refro

mTB

NA

negativ

eBA

Lcultu

resn

egative

Chem

otherapy/dem

ised

No

(diffuselarge

B-cell

lymph

oma)

949/M

Yes

New

diagno

sis/untreated

Cou

gh,n

onpu

rulent

sputum

/3mon

ths

Fever,appetite,and

weightloss/3weeks

Necrotic

mediastinal,rig

hthilara

ndrig

htsupraclavicular

lymph

adenop

athy,bilateral

pulm

onaryno

dules

(<10mm)

280

4R(30)

Bloo

dTB

cultu

refro

mTB

NA:

MTC

Treatedfor

MTC

/resolved

No

(TB)

HIV:H

uman

Immun

odeficiency

Virus,ART

:antire

troviraltherapy,T

BNA:T

ransbron

chialN

eedleAspira

tion,

BAL:

bron

choalveolarlavage,M

AC:m

ycob

acteriu

mavium

complex,T

B:tuberculosis,

MTC

:mycob

acteriu

mtuberculosiscomplex.

a According

totheInternatio

nalA

ssociatio

nforthe

Stud

yofL

ungCa

ncer

lymph

node

map

(200

9).2R:

right

upperp

aratracheal,4R

:right

lower

paratracheal,4L:left

lower

paratracheal,7:sub

carin

al,10L

:left

hilar.

4 BioMed Research International

use of a centralized database that was set up at the time ofintroduction of EBUS-TBNA to our institution. The studywas approved by our Centralized Institutional Review Board(2008/458/B). All cases of HIV infection were confirmedby Western blot. Demographic data, clinical presentations,results, clinical management, and outcomes are summarisedin Table 1.

Informed consent was obtained from each patient priorto the procedure. EBUS-TBNA was carried out in ourendoscopy suite under local anaesthesia and moderate seda-tion with midazolam and/or fentanyl.

3. Results

513 patients had EBUS-TBNA performed during this period.We identified nine HIV-infected patients who had LAD ofunknown cause that underwent EBUS-TBNA. The averageage of these HIV-infected patients was 52 years (range: 40to 73 years) and the average CD4 count was 197 (range: 2to 433 cells/mm3). The most common presenting symptomwas fever and the paratracheal lymph nodes were the mostfrequently sampled. The addition of EBUS-TBNA reducedthe need for mediastinoscopy in eight out of nine patients(Table 1).

All 5 cases of Mycobacterial infection were treatedwith Mycobacterial therapy, with clinical and radiologicalimprovement. One patient with small cell lung cancer diedbefore treatment was commenced (Patient 1). One patientwith diffuse large B-cell lymphoma received chemotherapybut died 10 weeks later from progressive disease (Patient 8)(Table 1).

Although an indeterminate result was recorded forPatient 2, he remains clinically well 22 months after EBUS-TBNA. Follow-up CT thorax 22 months later revealed stablemediastinal lymphadenopathy, partial resolution of axillarylymphadenopathy, andnonewfindings.Thus, hewas deemedto have nonspecific mediastinal lymphadenopathy. Similarly,Patient 6 remains clinically well on follow-up 24months afterEBUS-TBNA.

One complication was encountered. Patient 1 had anuneventful bronchoscopic procedure, but desaturated andhad an asystolic collapse 18 hours thereafter. Chest radiographdid not reveal any pneumothorax or new consolidation.He did not have any haemoptysis to suggest bleeding asa complication of the procedure. The cause of death wasattributed to an acute myocardial event, as he had significantcardiovascular risk factors (diabetes, hypertension, smoker).The case was referred to the coroner’s office but an autopsywas not performed.

4. Discussion

We found that EBUS-TBNA decreased the need for medi-astinoscopy in eight out of nine (89%) HIV patients withLAD. EBUS-TBNAwas able to diagnose four out of five casesof lymphadenopathy secondary to Mycobacterial infections,

one case of diffuse large B-cell lymphoma and one case ofsmall cell lung cancer. It was nondiagnostic in one caseof tuberculosis (diagnosed by mediastinoscopy). Althougha definitive diagnosis was not obtained in two patients,these patients had relatively small lymph node enlargement(≤15mm), which likely represented an inflammatory reactionto HIV infection, rather than actual lymph node involvement(i.e., “true negative” EBUS-TBNA procedures). Stability intheir conditions after 22 months and 24 months of follow-up further supports the conclusion that the lymphadenopathyobserved was unlikely to be clinically significant.

To our knowledge, this is the first series describing theutility of EBUS-TBNA in the diagnosis of LAD in HIV-infected patients, and our findings support the utilisation ofthis bronchoscopic technique in this group of patients.

Although there was a patient who died 18 hours afterbronchoscopy, this was likely due to the sedation and/orhypoxemia related to bronchoscopy, rather than EBUS-TBNA itself. Major complications from bronchoscopy areuncommon (0.08% to 0.5%), and so is mortality (up to0.04%) [8]. Based on a nation-wide survey involving 520centres in Japan, complications arising from EBUS-TBNAare also uncommon (1.2%), and mortality is rare (0.01%)[9]. The main complications were bleeding (0.68%) andinfection (0.19%) [9]. Our patient’s significant cardiovascularrisk factors of diabetes, hypertension, and smoking, as wellas the events leading to his demise, strongly suggest an acutemyocardial event. In general, complication and mortalityrates from bronchoscopy (0.08–0.5% and 0.04%, resp.) andEBUS-TBNA (1.2% and 0.01%, resp.) are still comparableto or lower than those of mediastinoscopy (1.07% and0.05%, resp.) [3]. In addition, EBUS-TBNA does not requiregeneral anaesthesia or an inpatient hospitalization in mostcentres.

The main limitations of our study are its retrospectivenature and small numbers. However, completeness of datais ensured by the centralized database that was set up at thetime of introduction of EBUS-TBNA to our institution, aswell as cross-checking of results with the Electronic HealthRecords. Secondly, patients referred for EBUS-TBNA werescreened for HIV infection only when there was clinicalsuspicion of the disease. We recognise that there may bepatients who have undergone EBUS-TBNA with concomi-tant undiagnosed HIV infection. Nevertheless, as a tertiaryreferral centre, we have a low threshold for ordering HIVtesting in patients. In fact, 33.3% (171 of 513 patients) of ourEBUS-TBNA cohort had undergone HIV testing. Therefore,we believe that we are unlikely to have underdiagnosed HIVinfection in our cohort of patients, and that our findings arerepresentative of real-life clinical practice.

In conclusion, it appears that potential mediastinoscopiescan be avoided by utilising EBUS-TBNA inHIV patients withintrathoracic lymphadenopathy.

Conflict of Interests

The authors declare that there is no conflict of interestsregarding the publication of this paper.

BioMed Research International 5

References

[1] R. M. Jasmer, M. B. Gotway, J. M. Creasman, W. R. Webb, K. J.Edinburgh, andL.Huang, “Clinical and radiographic predictorsof the etiology of computed tomography-diagnosed intratho-racic lymphadenopathy in HIV-infected patients,” Journal ofAcquired Immune Deficiency Syndromes, vol. 31, no. 3, pp. 291–298, 2002.

[2] P. Wannakrairot, T. Y.-M. Leong, and A. S.-Y. Leong, “Themorphological spectrum of lymphadenopathy in HIV infectedpatients,” Pathology, vol. 39, no. 2, pp. 223–227, 2007.

[3] A. Lemaire, I. Nikolic, T. Petersen et al., “Nine-year single centerexperience with cervical mediastinoscopy: complications andfalse negative rate,” Annals of Thoracic Surgery, vol. 82, no. 4,pp. 1185–1190, 2006.

[4] T. J. Harkin, C. Ciotoli, D. J. Addrizzo-Harris, D. P. Naidich,J. Jagirdar, and W. N. Rom, “Transbronchial needle aspiration(TBNA) in patients infected with HIV,” American Journal ofRespiratory and Critical Care Medicine, vol. 157, no. 6, part 1, pp.1913–1918, 1998.

[5] M. B. Wallace, J. M. S. Pascual, M. Raimondo et al., “Minimallyinvasive endoscopic staging of suspected lung cancer,” Journal ofthe American Medical Association, vol. 299, no. 5, pp. 540–546,2008.

[6] A. Tremblay, D. R. Stather, P. MacEachern, M. Khalil, andS. K. Field, “A randomized controlled trial of standard vsendobronchial ultrasonography-guided transbronchial needleaspiration in patients with suspected sarcoidosis,” Chest, vol.136, no. 2, pp. 340–346, 2009.

[7] N. Navani, P. L. Molyneaux, R. A. Breen et al., “Utility of endo-bronchial ultrasound-guided transbronchial needle aspirationin patients with tuberculous intrathoracic lymphadenopathy: amulticentre study,”Thorax, vol. 66, no. 10, pp. 889–893, 2011.

[8] British Thoracic Society Bronchoscopy Guidelines Committee,“British thoracic society guidelines on diagnostic flexible bron-choscopy,”Thorax, vol. 56, supplement 1, pp. i1–i21, 2001.

[9] F. Asano, M. Aoe, Y. Ohsaki et al., “Complications associatedwith endobronchial ultrasound-guided transbronchial needleaspiration: a nationwide survey by the Japan Society for Res-piratory Endoscopy,” Respiratory Research, vol. 14, no. 1, article50, 2013.

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Documents

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utilising ebustbna

addition of ebus

hiv infection1

lad of unknown cause

aik hau tan

diagnosis of lung cancer5