Co esponding au ho : So ia Vasile a Zabadano a
Copy igh © 2025 Au ho (s) e ain he copy igh o his a icle. This a icle is published unde he e ms o he C ea i e Commons A ibu ion License 4.0.
Diagnos ic and he apeu ic applica ions o B onchoscopic c yo echniques in lung
neoplasms: A li e a u e e iew
So ia Vasile a Zabadano a * and Geo gi S oyko Hinko
Depa men o Pulmonology, Mili a y Medical Academy, So ia, Bulga ia.
Wo ld Jou nal o Ad anced Resea ch and Re iews, 2025, 26(02), 926-934
Publica ion his o y: Recei ed on 30 Ma ch 2025; e ised on 06 May 2025; accep ed on 09 May 2025
A icle DOI: h ps://doi.o g/10.30574/wja .2025.26.2.1768
Abs ac
B onchoscopic c yo echniques ha e been used since he mid-20 h cen u y, ini ially o he apeu ic pu poses.
Subsequen modi ica ions in he echnology led o he eme gence o a new biopsy me hod, which became pa o he
diagnos ic p ocess o a ious lung diseases. T ansb onchial c yobiopsy is widely used o he diagnosis o pa ien s wi h
di use pa enchymal lung diseases. Due o he lowe isk o complica ions, a sho e hospi al s ay, and educed cos s, i
is a easonable al e na i e o su gical lung biopsy. The ole o c yobiopsy is also inc easing in pa ien s wi h cen al and
pe iphe al lung umo s, al hough he e a e s ill signi ican a ia ions in echnical p o ocols be ween di e en cen e s.
Keywo ds: Lung neoplasms; C yo he apy; C yobiopsy; T ansb onchial c yobiopsy
1. In oduc ion
The clinical p esen a ion o ai way s enosis due o malignan lesions co ela es wi h he deg ee o obs uc ion and i s
loca ion. Symp oms ange om mild dyspnea, cough, and hemop ysis o s ido and li e- h ea ening espi a o y ailu e
[1,2]
B onchoscopic echniques used in malignan cen al ai way obs uc ion o elie e symp oms and imp o e quali y o li e
include lase and a gon plasma coagula ion [3,4], elec ocau e y [5], pho odynamic he apy [6], endob onchial
b achy he apy [7], c yo he apy [8], mechanical debulking [9], s en ing [10]. The choice depends on ac o s such as
a ailabili y, ope a o expe ience, he need o immedia e e ec , and he ype o lesion (endoluminal, ex aluminal,
causing ex insic comp ession o mixed) [11].
In 1968, a igid c yop obe was used o he i s ime o ea an endob onchial umo [12]. Subsequen ly, wi h he
de elopmen o lexible c yop obes, he applica ion o b onchoscopic c yo echniques inc eased. To da e, endoscopic
sp ay c yo he apy sys ems a e also a ailable [13].
C yoabla ion was he i s c yo echnique used [14,15]. I is based on he Joule–Thomson p inciple, whe e a lique ied gas
unde p essu e expands in o a gaseous o m, leading o a dec ease in empe a u e. S opping he low and educing he
p essu e is ollowed by he elease o hea and hawing [13,16]. Repea ed cycles o apid eezing and slow hawing
cause cellula and ascula damage, wi h he end esul being he des uc ion o he a ge a ea [12,17]. A e se e al
days, subsequen b onchoscopic p ocedu es a e necessa y o emo e nec o ic issue [17,18].
C yo ecanaliza ion is a newe echnique ha uses c yoadhesion o he apeu ic pu poses [19-21]. The o ma ion o ice
c ys als upon eezing o he luid be ween he ip o he p obe and he a ge issue, as well as he luid wi hin he issue
i sel , esul s in he adhesion o he wo su aces [21]. While s ill ozen, he c yop obe is wi hd awn along wi h he
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b onchoscope. This app oach allows immedia e ea men o he endob onchial lesion and p o ides as e esul s
compa ed o he delayed esponse seen wi h c yoabla ion. This makes c yo ecanalisa ion a sui able echnique o
pa ien s wi h acu e symp oms due o ai way obs uc ion [19]. In addi ion, biopsy samples wi h well-p ese ed cellula
s uc u es and issue a chi ec u e can be ob ained o subsequen pa hoana omical s udies [22-24].
2. C yo ecanaliza ion
Among he ad an ages o c yo ecanaliza ion o e o he b onchoscopic echniques a e lowe cos s and a low isk o
ai way pe o a ion due o he c yo esis ance o ca ilage issue [19,25]. In addi ion, he p ocedu e can be pe o med in
an en i onmen wi h a high oxygen ac ion, unlike lase abla ion o example [19,25].
He zel e al. [19] we e he i s o e alua e he e ec i eness o c yo ecanaliza ion in pa ien s wi h exophy ic
endob onchial umo s and clinically signi ican ai way s enosis. A c yop obe wi h g ea e eezing powe and s abili y
agains ac ion was used compa ed o he c yoabla ion p obe. All p ocedu es in he s udy we e pe o med using a
lexible b onchoscope, wi h he du a ion o each anging om 9 o 81 minu es (mean 41 ± 16 minu es). Acco ding o
he in es iga o s, igid b onchoscopy was no necessa y bu should be a ailable o manage po en ial complica ions.
Pa ial o comple e success was achie ed in 83% o cases ega dless o umo ype o he loca ion o he ai way
obs uc ion ( achea, main o loba b onchi). In he emaining 17% (10 pa ien s), he s enosis was oo ex ensi e,
p e en ing access o he dis al espi a o y ac , an impo an p edic o o p ocedu al success. To educe he likelihood
o unsuccess ul in e en ions, he au ho s ecommend ca e ul pa ien selec ion and p e-p ocedu al assessmen o he
acheob onchial ee using imaging echniques such as i ual b onchoscopy and b onchog aphy.
A subsequen s udy by he same g oup o in es iga o s [20] epo ed success ul c yo ecanaliza ion in 205 o 223
pa ien s (91.1%). Acco ding o he au ho s, inc eased ope a o expe ience and e inemen o echnique we e possible
easons o he highe success a e compa ed o p e ious esul s. In mos cases, a lexible b onchoscope and
endo acheal ube we e u ilized (n=194; 86.2%).
Subsequen s udies in which c yo ecanaliza ion was used epo ed success a es anging om 72.5% o 95% [25-27].
Se e al ac o s in luencing he e ec i eness o he echnique ha e been analyzed, such as lesion localiza ion in he
cen al ai ways [25], he absence o dis al a elec asis [20,25,26], he du a ion o he obs uc ion [26], and he use o
addi ional me hods such as s en ing and balloon dila ion in cases o mixed lesions [25].
In a s udy by Ng B e al. [28], mos p ocedu es we e pe o med in an ou pa ien se ing (49/54 p ocedu es). An
imp o emen in espi a o y unc ion ollowing he p ocedu e (mean inc ease in FEV1 by 0.28L) and a low bleeding a e
(obse ed in wo pa ien s) we e epo ed. The e was no signi ican di e ence in pe o mance s a us be o e and a e
he in e en ion. Howe e , he esul s o ano he s udy [29] demons a ed an imp o emen in pe o mance s a us in
he majo i y o pa ien s (49/67 pa ien s), enabling subsequen chemo he apy. In addi ion, pa ien s who ecei ed bo h
chemo he apy and c yo he apy had a be e su i al compa ed o hose who unde wen c yo he apy alone.
Acco ding o s udies published o da e, he mos equen ly obse ed complica ions o c yo ecanaliza ion a e mild and
mode a e bleeding, wi h se e e and li e- h ea ening e en s being a e [19,20,25]. Schumann e al. [20] epo ed an
o e all bleeding a e o 12%, wi h mild bleeding in 4% and mode a e bleeding in 8% o pa ien s. Addi ionally, one case
o pneumomedias inum was obse ed in a pa ien wi h a acheal cys adenoma.
In he s udy by Ina y e al. [25], espi a o y ailu e equi ing in asi e mechanical en ila ion occu ed in se en pa ien s,
while wo pa ien s needed nonin asi e en ila ion. Fu he mo e, one pa ien had a mucosal wall de ec ollowing he
p ocedu e, wi hou p og ession o pneumomedias inum o pneumo ho ax.
A e ospec i e s udy o 208 pa ien s conduc ed in Seoul [27] analyzed he isk ac o s o bleeding du ing
b onchoscopic c yo ecanaliza ion. Acco ding o he esul s, diabe es melli us (associa ed wi h pe sis en ascula
damage and in lamma ion), espi a o y ailu e be o e he p ocedu e (sugges ing highe -g ade s enosis and he need o
a mo e in asi e in e en ion), and he absence o dis al a elec asis (leading o hypoxic asocons ic ion) we e
associa ed wi h an inc eased isk o mode a e and se e e bleeding e en s. In con as o p e ious epo s, he e was no
signi ican ela ionship wi h he his ological a ian o he umo . In one pa ien wi h obs uc ion o bo h main b onchi
due o me as ases om enal cell ca cinoma, a a al ou come occu ed due o se e e bleeding and espi a o y ailu e. In
addi ion, he da a sugges ha e en in mo e ex ensi e ai way in ol emen and he p esence o dis al a elec asis,
c yo ecanaliza ion can be success ul. Howe e , mul i a ia e logis ic eg ession analysis did no show a s a is ically
signi ican associa ion, and u he s udies a e needed.
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3. C yobiopsy
C yobiopsy enables he acquisi ion o la ge specimens wi h ewe a i ac s caused by mechanical damage compa ed o
con en ional o ceps biopsy (Figu e 1 and 2) [22-24]. In his way, issue a chi ec u e and cellula s uc u es a e
p ese ed, allowing o mo e accu a e his ological analysis [30-32].
Figu e 1 Di e ence in size be ween o ceps biopsy and c yobiopsy
Figu e 2 C yobiopsy samples
3.1. Cen al pulmona y lesions
Fibe op ic b onchoscopy wi h o ceps biopsy is he gold s anda d o he diagnosis o endob onchial lesions [33]. The
diagnos ic yield depends on se e al ac o s, including he ype o lesion [34], he numbe o samples ob ained [34-36],
and he use o addi ional echniques such as b ush biopsy, b onchoal eola la age, and endob onchial needle aspi a ion
biopsy [37,38].
Unlike o ceps, he c yop obe can be posi ioned bo h pe pendicula ly and angen ially o he a ge a ea, allowing
concen ic expansion o he eezing zone and sample acquisi ion om he dep h o he lesion (3) [19,21]. This is he
eason o he epo ed highe diagnos ic alue o c yobiopsy no only in exophy ic endob onchial lesions bu also in
hose wi h mucosal and submucosal in il a ion [19].
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Figu e 3 C yop obe can be posi ioned angen ially o he a ge a ea
Fewe c yobiopsies a e equi ed o his ological diagnosis and subsequen gene ic and immunohis ochemical analysis
[39-41]. Acco ding o a p ospec i e s udy [42], wo c yobiopsies a e he op imal numbe o making a de ini i e
diagnosis and a he same ime o minimal isk o complica ions. In compa ison, acco ding o he ecommenda ions, a
leas i e o ceps biopsies a e equi ed o isible endob onchial o ma ions in o de o achie e maximum diagnos ic
esul s [43].
Time o diagnosis is a key ac o in luencing he apeu ic ou comes and su i al. In he absence o his ological
e i ica ion o he imaging indings, epea b onchoscopy o addi ional in asi e p ocedu es a e equi ed, which a e
associa ed wi h inc eased cos s, highe isk o complica ions, and delays in diagnosis. A Czech s udy [44] ound ha , in
pa ien s wi h cen al lung neoplasms, c yobiopsy sho ens he ime o diagnosis compa ed o con en ional o ceps
biopsy. The p opo ion o pa ien s equi ing a second o hi d p ocedu e o es ablish a diagnosis was lowe in he
c yobiopsy g oup (2% s. 9%).
3.2. Pe iphe al pulmona y lesions
T ansb onchial c yobiopsy is widely used o diagnosing pa ien s wi h di use pa enchymal lung diseases [45,46]. Wi h
i s ad an ages in e ms o sho e hospi al s ay, lowe cos s, and lowe isk o complica ions, i may be an al e na i e o
su gical biopsy in selec ed pa ien s wi h pe iphe al lung neoplasms [47,48]. Va ious ac o s ha may in luence he
diagnos ic yield ha e been analyzed, such as he size and loca ion o he lesions [49-51], luo oscopic isibili y [50], use
o adial p obe endob onchial ul asound (RP-EBUS) wi h o wi hou a guide shea h [49,52,53], o ien a ion o he
lesions o he ul asound p obe [49,54], p esence o a b onchus sign [41,50,55], p obe size [49,55,56], and ope a o
expe ience [41,47].
One o he limi a ions o c yobiopsy is he di icul y in accessing ce ain lung egions, pa icula ly he uppe lobes, due
o he igidi y o he c yop obe [50,57]. In an a emp o o e come his limi a ions, newe disposable c yop obes wi h
smalle ou e diame e s and enhanced lexibili y ha e been de eloped [49,55,56]. In addi ion, he 1.1 mm diame e
c yop obe can be emo ed along wi h he biopsy issue in ce ain condi ions (such as using an op imal ac i a ion
du a ion and a b onchoscope wi h a su icien ly la ge wo king channel) [54]. In his way, he b onchoscope emains in
he ai way h oughou he p ocedu e, ensu ing be e con ol. Any bleeding can be p omp ly assessed, and hemos asis
me hods can be applied.
Radial p obe endob onchial ul asound (RP-EBUS) is a guided imaging echnique ha can also be u ilized o
ansb onchial c yobiopsy o pe iphe al lesions [51,53,54]. Due o i s abili y o pe o m la e al biopsies, he
c yo echnique enhances diagnos ic yield in eccen ically and adjacen ly o ien ed RP-EBUS lesions. [54].
3.3. Complica ions
Acco ding o he a ailable s udies, he mos common complica ions associa ed wi h c yobiopsy o lung lesions a e mild
o mode a e bleeding [19,20,39,40]. Va ious ac o s ha may in luence he incidence o bleeding ha e been in es iga ed.
In a s udy o pa ien s wi h endob onchial umo s [42], a highe isk was epo ed when mo e han h ee c yobiopsies
we e aken. The use o adial p obe endob onchial ul asound (RP-EBUS) allows o he isualiza ion o la ge blood
essels, po en ially minimizing he isk o hemo hagic complica ions [58]. Some in es iga o s use an endob onchial
blocke [57] o a wo-b onchoscope echnique [59] du ing ansb onchial c yobiopsy o u he educe he bleeding
a e.
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4. Conclusion
B onchoscopic c yo echniques play a signi ican ole in bo h he diagnos ic and he apeu ic managemen o pulmona y
neoplasms. C yobiopsy p o ides high-quali y specimens wi h well-p ese ed cellula s uc u es and issue a chi ec u e
o mo e p ecise pa hoana omical s udies. Among he key ad an ages o c yo ecanaliza ion a e i s ela i ely low cos ,
minimal isk o ai way pe o a ion, and he abili y o pe o m he p ocedu e in en i onmen s wi h high oxygen
concen a ions. Fu he mo e, he incidence o se e e and li e- h ea ening complica ions associa ed wi h hese
p ocedu es is epo ed o be low.
Compliance wi h e hical s anda ds
Disclosu e o con lic o in e es
No con lic o in e es o be disclosed.
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