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Ростовский Государственный Медицинский Университет

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CHAPTER 5 Transbronchial Cryobiopsy for Diffuse Lung Diseases

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4. Pumnary funtin tests: Dlco shud be >35%, fred vita apaity (FVC) > 50%, and tta ung

apaity (TLC) > 50% prediated.

A Dlco f <35% inreases the prbabiity f adverse utmes and mrtaity at 30 and 90 days.

5. Hypxia: Pao

> 55–60 r an Spo

> 90% whie n 2 L

f xygen via nasa annua is nsidered a requirement by sme, whie thers nsider any use f suppement xygen a ntraindiatin. Intrapredura tehniques t assess the patient’s abiity t safey terate transient peribipsy hypxia are detaied ater.

4,14

6. Obesity: ere shud be n signiant abdmina

besity. A BMI <35–40 kg/m

is nsidered by sme t be a reasnabe ut- vaue. Signiant abdmina besity may make it diut t mpete the predure due t the rapid devepment f ateetasis and inreased risk f peripredura hypxemia.

7. Pumnary hypertensin: A transthrai ehardigram is usuay suient and is remmended t btain befre the predure as many patients with DPLD may have existent pumnary arteria hypertensin. Pumnary artery systi pressure ess than 50mmHg with nrma right ventriuar funtin is

8,9,15

remmended.

marker t exude signiant pumnary hypertensin.

Sme enters use BNP as a surrgate

8. Cmrbid media nditins: Unntred hypertensin, ngestive heart faiure, ishemi heart disease, ESRD n diaysis, severe arti stensis, signiant entribuar emphysema r buus ung disease in the area f bipsy, and thrmbembi disease unabe t stp antiaguatin r with signifiant right heart dysfuntin are nsidered ntraindiatins t TBCB.

Equipment

1. 1.9 mm r 2.4 ERBE ryprbe (ERBE, Marietta, GA, USA)

2. ERBE ry mahine with CO

3. Fexibe brnhspe with minimum 2.8-mm wrking hanne fr 2.4-mm prbe (arger wrking hanne remmended fr greater sutin apaity if nt using rigid brnhspy)

4. Rigid brnhspe (peratr dependent)

5. Rigid sutin atheter (peratr dependent)

6. Brnhia bker (Arndt r Fgarty ban; Arndt 7 r 9 Frenh; the ban shud be arge enugh that, when inated, it bstruts the segmenta r mainstem brnhi prxima t the site f the bipsy)

r N

O gas

7. Endtrahea tube (standard r wire-reinfred)

8. C-arm urspy mahine

9. Basin with nrma saine

10. Frmain speimen etin ntainers

11. Ied saine r ther vasnstritr agent

Staff

1. Brnhspist

2. Send brnhspist r trained brnhspy tehniian t assist with prphyati ban inatin

3. Brnhspy tehniian t assist with speimen etin

4. Anesthesia prvider

5. Brnhspy nurse t administer sedative mediatins and mnitr the patient, if required

Setting

Latin suitabe fr genera anesthesia (brnhspy suite r peratr rm).

PROCEDURAL TECHNIQUES

Flexible Bronchoscopy Approach

• Anesthesia, ventilation, and airway Genera anesthesia, with r withut neurmusuar bkade with paement f an ETT, prvides a seure airway in the event f massive airway hemrrhage. By eiminating the ugh reex, risk f mapsitin f the ryprbe during the predure with the unintended nsequene f mving the prbe either t far int the periphery r t prxima in the hest is redued. Psitive end-expiratry pressure shud be kept at a minimum (maximum 5 mH

One f the benets f using an ETT is the apprpriate paement f an endbrnhia ban bker. ere are tw methds fr paement f the endbrnhia bker in reatin t the ETT: (1) within the ETT r (2) externa t the ETT. If the endbrnhia bker is passed within the ETT, the patient is rst intubated in the standard manner. An Arndt endbrnhia bker is passed thrugh the ETT nnetr and seured t the tip f the exibe brnhspe. e nnetr with the endbrnhia bker attahed t the brnhspe is then attahed t the ETT and the ban bker is guided thrugh the ETT and psitined prxima t the

O).

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Fig. 5.2 Placement of Arndt endobronchial balloon

blocker. The Arndt balloon blocker kit comes with an endotracheal tube (ETT) connector (yellow star) that attaches to the ETT. The endobronchial balloon blocker is passed through the connector (blue arrow) and meets the bronchoscope that was passed through the connector (red arrow). The blocker is secured to the tip of the bronchoscope (yellow arrow). The entire apparatus is then attached to the ETT.

SECTION 1 Advanced Diagnostic Bronchoscopy Procedures

airway segments being bipsied (Figs. 5.2 and 5.3). One ptentia imitatin t this apprah is that the ban may ause partia bstrutin f the ETT and impair remva f the brnhspe and ryprbe fwing bipsy, raising the risk f ban disdgement. Aternativey, the endbrnhia bker may be externa t the ETT. With this methd, the patient is berptiay intubated (either awake berpti intubatin, fwed by tta intravenus anesthesia [TIVA] ne the tube has been seured r berpti intubatin fwing indutin with anesthesia) with an Arndt endbrnhia bker psitined “piggybak” angside the ETT (Fig.5.4). is aws ease f paement f the ban bker at time f anesthesia indutin withut bstruting the ETT (Fig. 5.5).

One ptentia advantage f the ETT with an externa bker tehnique is the abiity t seetivey intubate the ntraatera ung in the setting f severe hemrrhage whie eaving the ban in pae n the beeding side. If the ban is paed in the umen f the ETT, the ban wud have t be deated and retrated in rder t pass the ETT int the ntraatera mainstem brnhi. A exibe spira, wire-reinfred ETT (Fig. 5.6) is usefu in these irumstanes and faiitates easy insertin int the mre anguated

A B

Fig. 5.3 Position of the bronchial blocker in the bronchus intermedius. (A) Correct positioning

of the bronchial blocker in the bronchus intermedius. Right middle lobe (white arrow), superior segment (black arrow), remaining right lower lobe segments (red arrow). (B) Fully inated bal- loon occluding all segments. This is a test ination for (1) balloon integrity and (2) assessment of patient’s physiologic response to balloon occlusion. If the patient becomes hypoxic with this maneuver, the procedure is aborted.

CHAPTER 5 Transbronchial Cryobiopsy for Diffuse Lung Diseases

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B C

Fig. 5.4 Conguration of bronchial blocker external to the tube. (A) The bronchial blocker secured

at the distal end of the bronchoscope. (B) Endotracheal tube loaded on bronchoscope and secured with tape. (C) Bronchial blocker attached to suction apparatus on bronchoscope with hemostat. Hemostat maintains cinch attachment of blocker to bronchoscope.

A B

Fig. 5.5 Bronchial blocker positioned external to the endotracheal tube. (A) Patient intubated with

endotracheal tube. Bronchial blocker is passing external to the endotracheal tube (black arrow). Syringe attached to blocker to inate the balloon (white arrow). (B) Bronchoscopic view of distal end of endotracheal tube. Yellow bronchial blocker catheter is passing external to the endotracheal tube and is directed into the right mainstem.

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Fig. 5.6 Spiral wire reinforced endotracheal tube. An

8.5-mm internal diameter endotracheal tube.

SECTION 1 Advanced Diagnostic Bronchoscopy Procedures

e mainstem brnhus if bipsies are taken in the right ung and massive beeding is enuntered.

• Use of prophylactic balloon blocker and bleeding

prevention

Beeding is a majr nern with this predure and preventin and expertise in ntring airway hemrrhage is f primary imprtane. One apprpriate patient seetin has been dne and the airway seured with either an ETT r rigid brnhspe, the prphyati endbrnhia bker is psitined prxima t the segment t be bipsied (Fig. 5.3). e use f a brnhia bker (Arndt r Fgarty ban) is nsidered mandatry by guideines. Beause the arge size f the bipsy speimens requires the brnhspe and ryprbe t be remved en b aer a bipsy is taken, the airway remains unprteted and withut a brnhia bker in the airway at the start f the predure, vauabe sends are st as bd rapidy s the anatmi dead spae with risk f asphyxiatin and death. It is imprtant t test the ban prir t airway insertin t detet defets that wud prevent prper ban usin during the predure. One the ban is in psitin, a test inatin shud be perfrmed t determine the patient’s physigi respnse t ban usin. If the patient bemes hypxi during the test inatin, the predure shud be abrted. One the bipsy is taken, the ban is then immediatey inated by a send brnhspist r trained assistant. Aer the bipsy is transferred t a saine basin, the brnhspe is rapidy reinserted int the airway and the

ban is deated aer the spe is psitined in frnt f the inated ban (Fig. 5.7). e speimen is then transferred frm the saine basin t the xative f hie, typiay frmain. Mid-t-mderate beeding an then be ntred with sutin, spe tampnade, r ied saine at the disretin f the brnhspist. If beeding is severe and ntinues with these measures, then the ban is reinated t tampnade the beeding and prevent siing f additina airways. is tehnique was riginay desribed with rigid brnhspy but then was adpted t aw paement f the ban externa t the ETT as desribed earier.

18,19

e appiatin f urspy is essentia t ensure that bipsies are taken as se t the peura as pssibe t ensure representative samping f diseased ung parenhyma (within 1m f the peura is remmended) whie as making sure that the prbe is nt t prxima s as t avid arge bd vesses and ause severe beeding. Withut the use f urspy, the sti ryprbe may beme dged mre prximay than reaized due t distrted airways r airway bifuratins if the brnhspist sey reies n tatie feedbak. Sme degree f beeding shud be expeted with TBCB but the use f urspy may hep mitigate this risk. Reprts f severe beeding have urred in situatins in whih urspy was nt empyed.

e use f radia endbrnhia utrasund (rEBUS) has been suggested as a means t redue beeding by identifying vesses and thus direted the ryprbe t ung tissue devid f vasuature. Currenty the data are niting n its use in reduing beeding and this remains an area f ative investigatin.

21,22

• Cryoprobe size and freezing time One the airway has been seured and the prphyati ban bker has been rrety psitined, the ryprbe is advaned int the segment f hie under urspi guidane. e size f ryprbe used (1.9mm vs. 2.4mm) is peratr dependent but there may be a higher risk f pneumthrax with the

2.4-mm prbe.

N signiant dierenes in diagnsti yied have been identied. Current guideines remmend use f the 1.9-mm prbe fr this reasn.

smaer size may prvide easier tatie feedbak when the prbe makes ntat with the peura.

e size f the sampe wi depend n the surfae area f the prbe and the duratin f prbe ativatin. As a genera rue, the nger the ativatin time,

e

CHAPTER 5 Transbronchial Cryobiopsy for Diffuse Lung Diseases

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A B

Fig. 5.7 Prophylactic bronchial blocker inated immediately after biopsy. (A) Fully inated bron-

chial blocker immediately after biopsy was taken from the right lower lobe. (B) Balloon is deated once the bronchoscope is repositioned in the airway and careful inspection can be performed. Suctioning, scope tamponade, administration of vasoconstrictor agents, or immediate reination of the balloon can be performed for bleeding control if needed.

A B

Fig. 5.8 Test freezing the cryoprobe. (A) Test freezing the cryoprobe. (B) Freeze ball should be

approximately 5mm in size. Freezing times vary to achieve this size.

the greater the sampe size. Mst freezing times are between 4 and 7 s with wide ranges f tissue sampe sizes (9–64.2 mm).

An en frgtten but imprtant step befre the rst bipsy is taken is t test the time it takes fr the prbe t generate a 5-mm ie ba (Fig. 5.8). Beause the pressure f the gas (CO

direty impats the rapidity with whih the tip f

the prbe freezes, it is nt unmmn fr a fu CO

tank t frm a arge ie ba within 3–4 s. If the prbe

freeze time is up t 7s in this situatin, a substantiay arger speimen than antiipated may be btained, inreasing risk f mpiatins.

• Cryoprobe distance to pleura

r N

O) in the yinder

One the patient has a seure airway, the prphyati ban bker is in pae, and the urspy

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SECTION 1 Advanced Diagnostic Bronchoscopy Procedures

C-arm is in psitin, the ryprbe is advaned thrugh the wrking hanne f the therapeuti brnhspe, int the target segment and direted se t the edge f the peura under urspi guidane. e ptima distane between the prbe and the peura is essentia fr bth safety and diagnsti yied, as sampes <1 m frm the peura signianty inrease pneumthrax rates apprahing

19,23,24

30%.

Adjusting the ryprbe within 2m f the peura has the added advantage f samping sma airways and with ptentia gd suess in

diagnsing nstritive brnhiitis.

e ptima distane f ryprbe that is urrenty remmended is 1 m frm the peura. Latera airways are preferabe whenever pssibe t assist with aurate psitining f the prbe t the peura. Under diret urspi guidane, the ryprbe shud be advaned unti resistane is fet (nsidered t be in ntat with the peura). One the edge f the peura has been reahed, the prbe is retrated 1 m, whih an be estimated frm the ength f the metai tip f the ryprbe, whih measures 1 m (Fig. 5.9).

• Location and number of biopsies e atin f the bipsy wi vary between patients and is dependent n the atin and extent f disease as we as tehnia fatrs in advanement f the ryprbe and psitin f the ban bker. It is remmended that bipsies be taken frm tw dierent sites: either a dierent segment within the same be r a

dierent ipsiatera be. is paraes vide-assisted

thraspi surgery (VATS)-SLB tehnique.

It as redues hanes f misdiagnsis sine tw dierent histgi diagnses may be seen in dierent bes.

27,28

It shud be kept in mind that the risk f pneumthrax may inrease if tw dierent sites are hsen.

e number f bipsies per segment r be is nt standardized and is generay peratr dependent. Hwever, it is remmended that three t ve bipsies be btained.

• Processing and collection of the specimen e TBCB sampes shud be handed with are t prevent rush artifat and aw pattern regnitin. One the bipsy is taken and the spe is remved frm the airway en b, the ryprbe with the sampe attahed is paed int saine. e bipsy is then mved genty frm saine and paed int frmain (Fig. 5.10). e bipsy shud then be embedded and riented int paran t maximize surfae area n the sides.

Rigid Bronchoscopy Approach

In genera, the prinipes fr eah mpnent f the predure as detaied earier fr the exibe brnhspy apprah are the same as fr rigid brnhspy with the exeptin f sme detais as it reates t ventiatin and ban bker. e ptentia advantages t the rigid brnhspy apprah inude the additin f a arge sutin devie in the event f severe beeding and

A B

Fig. 5.9 Positioning of cryoprobe with uoroscopy. (A) Cryoprobe is advanced until the pleural

edge is reached. (B) The probe is pulled back 1 cm from the pleural edge. This is estimated based upon the metallic tip of the cryoprobe being 1 cm in length. This is the location where the biopsy is taken.

CHAPTER 5 Transbronchial Cryobiopsy for Diffuse Lung Diseases

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A B

Fig. 5.10 Collection of cryobiopsy specimen. (A) Transfer of cryobiopsy specimen from saline con-

tainer to formalin with blunt tip needle and syringe. (B) Freshly obtained cryobiopsy specimens.

a arge ventiating umen that aws passage f a therapeuti brnhspe, endbrnhia brnhia bker, and sutin.

• Anesthesia, ventilation, and airway With the rigid brnhspy apprah, the patient shud be intubated as per institutina standard perating predures. Sanders’ jet ventiatin has mst en been reprted in the iterature as this aws fr an pen system and permits rapid entry int and ut f the airway, whih is ritia with this predure. Sedatin is ahieved with TIVA and administratin f paraytis. It is imprtant t aw fr adequate exhaatin time in rder t prevent aumuatin f psitive pressure, thus inreasing the risk fr pneumthrax. Bipsies shud be taken between breaths if pssibe t redue this risk as we. If nventina ventiatin is used with rigid brnhspy, then the same ventiatry prinipes appy as fr exibe brnhspy.

• Use of prophylactic balloon blocker and bleeding

prevention

A prphyati ban bker is sti required with rigid brnhspy. An endbrnhia ban bker an be passed dwn the umen f the rigid spe and psitined prxima t the segment t be

bipsied. e same predures fr test inatin and ban inatin pstbipsy are the same as detaied earier.

• Performing biopsies e ryprbe is tested fr the exat freeze time t ahieve a 5-mm ie ba. e ryprbe is then advaned thrugh the umen f a therapeuti exibe brnhspe. e exibe spe is then advaned thrugh the rigid brnhspe and t the segment t be bipsied. e rybipsies are perfrmed under urspi guidane and the exibe spe with the ryprbe and speimen is remved en b thrugh the rigid brnhspe. e speimen is freed frm the ryprbe in saine and then transferred t frmain. e exibe brnhspe is then passed thrugh the rigid brnhspe, paed immediatey in frnt f the inated ban, and then the ban is deated and evidene fr beeding is bserved. Beeding may then be ntred with sutin, exibe spe tampnade, r reinatin f the ban if beeding is brisk.

COMPLICATIONS

e safety f rybipsy has been a ntentius issue with high reprts f mpiatin rates seen in situatins

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SECTION 1 Advanced Diagnostic Bronchoscopy Procedures

in whih the predure was nt standardized. With the intrdutin f guideine statements undersring key eements t standardize the tehnique t imprve safety, this shud beme ess f a hindrane t perfrming the predure.

In tta, mpiatins ur in rughy 25% f ases,

with the mst mmn being beeding and pneumth-

rax (Tabe 5.2).

Sme degree f beeding is expeted with TBCB and ak f a unifrm beeding severity sre, dierenes in perfrming the predure, and dierenes in size f the ryprbe used have made it prbemati in determining its preise prevaene and assiated risk fatrs. Mderate beeding, as dened by ntr f beeding with endbrnhia bker r administratin f ied saine, urs in apprximatey 9%–14% f subjets; severe beeding (hemdynami mprmise, ICU admissin, surgia interventin, r ative tampnade

9,29

interventins) has an inidene f 1%.

Severe beeding is fet t be mre ikey when bipsies are taken in the entra znes due t the size f adjaent brnhia arteries. Frm a pratia standpint, hwever, it an be diut t determine the exat atin f the ryprbe in the hemithrax n a tw-dimensina (2D) urspy C-arm depending n the be and segment being bipsied and the rientatin f the C-arm t the thrax.

Pneumthrax urs in 9% f patients. e rate appears t be reated t (1) the number f sampes taken, (2) prximity f the prbe t the peura, (3) use f a 1.9-mm r 2.4-mm ryprbe, (4) UIP pattern n histpathgy, (5) brti retiuatin n HRCT, and (6) whether the bipsy was in the upper r wer bes. e

2.4-mm prbe, mre than ne bipsy site, and bipsy f the wer bes is assiated with a higher pneum-

thrax rate.

Chest tube paement is mmn in these

situatins (70%).

Exaerbatin f underying interstitia ung disease (ILD) urs in 0.3% f TBCB and is prbaby mre prevaent in individuas wh are hspitaized due t an

13,24

exaerbatin f their ILD.

is rate remains wer

than fr SLB (3%).

e vera predura mrtaity rate has been nsistenty reprted ess than 1% with ped rates vary-

5,29–32

ing between 0.3% and 0.5%.

e 30- and 90-day mrtaity rate may apprah 2.0%, with at-risk individuas being thse wh are hspitaized and/r had a wrsening f their disease befre bipsy, severe intrapredura hemrrhage, and a Dlco f ess than 35%.

With gd patient seetin, this mrtaity rate shud imprve.

Rare mpiatins inude avitary absess, pneum-

mediastinum, brnhia aeratin, and seizures.

24,33–35

TABLE 5.2 Complications of

Transbronchial Cryobiopsy

Complication Rate

Moderate bleeding 9%

Severe bleeding 1%

Pneumothorax 9.4%

Exacerbation of IPF 0.3%

Prolonged air leak 0.3%

Transient respiratory failure 0.7%

Seizures 0.7%

Pneumomediastinum One case reported

Cavitary abscess Three cases reported

Bronchial laceration One case reported

Death 0.5%

Highly variable and dependent on bleeding classication used; one meta-analysis found rate of combined moderate and severe bleeding of 14%.

IPF, Idiopathic pulmonary brosis.

EVIDENCE

Overall Pooled Diagnostic Yield of Transbronchial Cryobiopsy

Diagnsti yied is variabe between studies ranging frm 44% t 90% and is dependent n whether diagnsis was nrmed by histpathgy r MDD.

genera, the ped diagnsti yied is 72%.

tributin f the MDD annt be verstated as denite diagnsis may imprve by as muh as 24% when input frm an MDD is nsidered (e.g., 44% t 68%).

ritia as the MDD (with a inia, radigraphi, and pathgi data) remains the gd standard fr diagnsis and, nt infrequenty, the histpathgi diagnsis may dier frm the na MDD diagnsis.

Transbronchial Cryobiopsy Versus Transbronchial Biopsy

Cnventina TBBx has a pr histpathgi nrdane with SLB and a reativey w diagnsti yied

23,36

e n-

is is

CHAPTER 5 Transbronchial Cryobiopsy for Diffuse Lung Diseases

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1,37–39

(36%) in DPLD.

In the ny randmized tria mparing TBCB t TBBx, mre histpathgi diagnses were made in the TBCB grup than in the TBBx grup

(74.4% vs. 34.1%, P < 0.001).

mmended in the diagnsis f IPF.

As suh, TBBx is nt re-

Tissue speimens were signianty arger with TBCB (mean area size f 14.7 [±11 mm

] vs. 3.3 ± 4.1 mm

, P < 0.001). is arger speimen size with TBCB has been nsistenty reprted arss the iterature (Fig. 5.1).

Transbronchial Cryobiopsy Versus SLB

e best data t date mparing TBCB t SLB me frm a study f 65 patients wh were deemed by an MDD t need a tissue sampe and wh underwent TBCB f tw dierent bes fwed by VATS-SLB bipsy f the same bes during the same anesthesia.

ree pathgists were binded t the aquisitin f the speimens and they were anayzed randmy in a nnsequentia manner (a tta f 130 sides). ey were then disussed by an expert MDD, with a members binded tward the type f bipsy. ey reprted a raw histpathgi agreement fr guideine-rened patterns f

70.8% between TBCB and SLB (ƙ = 0.7 [95% CI, 0.55–

0.86]). Fr the na MDD diagnsis, the raw agreement between the tw methds was 76.9% (ƙ = 0.62 [0.47–

0.78]). Fr thse that were assied as having a highy ndent r denite diagnsis by MDD, 60% (39/65) were by TBC and 74% (48/65) by SLB (P = 0.09). Using MDD as the gd standard, the diagnsis was hanged frm a w ndene t high ndene/denite in 74% (48/65) and 77% (50/65), P = 0.55 f TBCB and SLB, respetivey, and msty by hanging frm an unassiabe diagnsis t a mre spei diagnsis. Interestingy, neither TBCB nr SLB was abe t prvide additina diagnsti ariatin in 12% f ases. ese resuts prvide nvining evidene that the additin f TBCB data t an MDD mprmised f experts in ILD prvides as usefu infrmatin as SLB and, assuming the safety pre and perfrmane f the predure an be standardized, make TBCB an attrative and reasnabe rst-ine bipsy tehnique in the evauatin f ILD.

FUTURE DIRECTIONS

Whie TBCB hds prmise as a nnsurgia aternative in the diagnsis f DPLD, questins remain. Safety f the predure sti remains a nern and the ak f predura standardizatin within and arss enters

remains a prbem that guideine statements hpe t mitigate. Optima patient seetin, prbe size, number f segments and bes t bipsy, use f REBUS, and training mpeteny as remain areas f ative researh. It is as unknwn what re genmi testing wi pay in the diagnsti agrithm f UIP/IPF and the interfae this wi have with bipsy speimens. e devepment f a rybipsy registry is needed t trak the utmes f these predures and prvide quaity and safety feedbak t enters, brnhspists, institutins, and the pubi. In the meantime, it wud be wise fr interventina pumngists t devep institutina predura prts t ensure maximum diagnsti yied and safety.

S U M M A RY

TBCB is a reativey new bipsy tehnique in the diagnsis f DPLD. It prvides usefu histpathgi infrmatin that an be inrprated int the MDD disussin t psitivey inuene a denitive diagnsti utme. e diagnsti ntributin f TBCB is superir t TBBx and is gd when mpared t SLB. As suh, it remains a gd initia diagnsti predure in patients with DPLD. e safety pre f TBCB has been ntentius with severe beeding being the mst nern. With the institutin f guideine statements that stress the rutine use f genera anesthesia, ETT r rigid brnhspy, urspy, and a prphyati ban bker, the safety pre is expeted t inrease.

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