WABIP Newsletter 2021, Issue 2

Volume 09

Issue 02

May 2021

Inside This Issue

Editorial, 2-3

Technology Corner, 4-5

Tips from the Experts, 6-9

Humanitarian News, 10-14

Best Image Contest, 15

WABIP News, 16

Research, 17

Links, 18

Editorial: The Role of Liquid Biopsy in the

Management of Non-small Cell Carcinoma

WABIP Newsletter

M A Y 2 0 2 1 V O L U M E 9 , I S S U E 2

EXECUTIVE BOARD

Hideo Saka, MD

Japan, Chair

Stefano Gasparini,

Italy, Vice-Chair

Silvia Quadrelli, MD

Argenna, Immediate

Past-Chair

David Fielding MD

Australia, Treasurer

Naofumi Shinagawa,

Japan,

Secretary General

Philippe Astoul, MD

France, President

WCBIP 2022

Menaldi Rasmin, MD

Indonesia, President

WCBIP 2024

STAFF

Michael Mendoza

General Manager

Judy McConnell

Administrator

Kazuhiro Yasufuku

Newsleer Editor-in-

chief

P A G E 2

Peter B Illei, MD

Associate Professor of Pathology and Oncology

Department of Pathology

Johns Hopkins University School of Medicine

Lung cancer is the second most common cancer

type with an esmated 228,000 new cases and

135,700 death annually represenng nearly 13% of

all cancer diagnoses and 22% of all cancer death in

the United States

. Strategies to reduce lung cancer

death include prevenon by eliminang risk factors

(i.e. reduce smoking and other toxic inhalants like

radon), early detecon by developing screening

guidelines, and providing personalized therapy

both for locoregional and metastac disease.

Nearly 50% of all lung cancers are non-squamous

non-small cell carcinomas the majority of which

being adenocarcinomas. Approximately 60% of

these tumors are known to have a driver genec

alteraon. Personalized therapy requires accurate

histologic diagnosis and staging together with iden-

caon of targetable genec alteraons (EGFR,

ALK, ROS1, BRAF etc.) and predicve biomarkers

(PD-L1). Pathologic classicaon requires a ssue

or cytology sample and the gold standard for mo-

lecular studies is also ssue-based. Close to half

(49%) of non-small cell carcinomas are diagnosed

as advanced stage (IIIB or IV) disease and the diag-

nosis is typically is based on a biopsy of the primary

tumor or a metastasis

. This can result in small

samples containing insucient tumor for biomarker analysis.

This is parcularly true for hard-to-reach small lung nodules,

in the presence of marked necrosis and samples of meta-

stac mediasnal lymph nodes with minimal to low tumor

burden. Similarly, a subset of loco-regional disease is not

amenable to surgical intervenon and therefore needs a bi-

opsy to establish the diagnosis. Current NCCN guidelines re-

quire tesng for targetable alteraons with FDA-approved

therapy (EGFR, ALK, ROS1, BRAF, NTRK, METexon14) all non-

squamous non-small cell carcinomas, and squamous cell car-

cinomas of never or former light smokers. In addion, EGFR

mutaon tesng should be performed in stage IB-IIIA adeno-

carcinomas, and PD-L1 should be assessed in all non-small

cell carcinomas

. There is a need for an alternave tesng

method for paents who are not candidates for a biopsy or

whose biopsy resulted in insucient ssue for biomarkers.

Cell-free DNA (cfDNA) is a product of dying non-neoplasc

cells (mostly white blood cells) that can be detected in the

blood/plasma and other body uids as can be cell-free tumor

DNA (ctDNA) and exosome DNA. The amount of circulang

ctDNA is determined by the number of tumor cells shedding

into the bloodstream, which varies between tumor types and

tumor stage. Liquid biopsy is a test that examines the pres-

ence of ctDNA, circulang tumor cells, or exosome DNA in

various types of body uids (i.e. plasma, pleural uid, cere-

brospinal uid etc.). Liquid biopsy can be used to detect mu-

taons, translocaons, copy number alteraons, and allele

frequency at inial diagnosis, as well as when monitoring

disease recurrence or therapeuc responses. Several dier-

ent assay types are being used and they can be grouped

based on the number of genes targeted, namely as single

gene or mul-gene assay. Single gene assays use highly sensi-

ve PCR-based methods (i.e. real-me PCR, digital droplet

PCR), while most mul-gene assays use next-generaon se-

quencing (NGS). Single gene assays require more tumor DNA

and higher tumor content and can only detect mutaons that

are specically targeted by the assay. In contrast, NGS assays

 
W A B I P   N E W S L E T T E R  
P A G E   3  
ents. The role of liquid biopsy with current approved methods in 
early-stage disease is in the experimental phase and the sensivity 
needs to be improved before widespread adaptaon can be done. 
Future  trends  include  improving  sensivity  and  specicity  of  the 
molecular assays, developing new methods that can detect epige-
nec changes of targetable  alteraons,  as  well as tumor-specic 
genome-wide  DNA  proles  including  epigenec  (methylaon) 
paerns  using  cfDNA  as  the  source
15
.  This  approach  could  help 
develop  a  blood-based  screening  tool  for  early  detecon  of  tu-
mors,  targetable  alteraons  and  potenally  provide  prognosc 
informaon  regarding  disease  recurrence  and  therapeuc  re-
sponse.  
 
 
 
 
 
References: 
1. Incidence of lung cancer. hps://seer.cancer.gov/staacts/html/
lungb.html#content (accessed 04/05/2021). 
2. Heist RS et al. Cancer Cell. 2012; 21(3): 448.e2. 
3. NCCN Clinical Pracce Guidelines in Oncology (NCCN Guidelines®) for 
Non-Small Cell Lung Cancer V.4.2021. hps://
www.precisiononcologynews.com/sites/default/les/
nccn_nsclc_guidelines.pdf (accessed 04/08/2021). 
4. Cobas EGFR Mutaon test v2 FDA approval. hps://www.fda.gov/
drugs/resources-informaon-approved-drugs/cobas-egfr-mutaon-test-
v2 (accessed 4/20/2021). 
5. FDA Approves First Liquid Biopsy Next-Generaon Sequencing Com-
panion Diagnosc Test. 4/20/2021. hps://www.fda.gov/news-events/
press-announcements/fda-approves-rst-liquid-biopsy-next-generaon-
sequencing-companion-diagnosc-test (accessed 04/19/2021). 
6. FoundaonOne Liquid CDx. 04/20/2021. hps://www.fda.gov/
medical-devices/recently-approved-devices/foundaonone-liquid-cdx-
p190032 (accessed 04/19/2021). 
7. Aggarwal C et al.  JAMA Oncol. 2019; 5(2): 173-80. 
8. Chen Y et al. Neoplasma. 2019; 66(4): 652-60. 
9. Zhang B et al. Lung Cancer. 2019; 134: 108-16. 
10. D'Angelo SP et al.  J Thorac Oncol. 2012; 7(12): 1815-22. 
11. Jiang J et al. J Mol Diagn. 2020; 22(2): 228-35. 
12. Liu Y et al. Transl Lung Cancer Res. 2021; 10(2): 914-25. 
13. Satapathy S et al. Curr Probl Cancer. 2021: 100722. 
14. Lee SE et al. Transl Lung Cancer Res. 2021; 10(1): 104-16. 
15. Crisano S et al. Nature. 2019; 570(7761): 385-9. 
require  less  DNA  and  lower  tumor  content,  can  detect  un-
known  mutaons  (hybrid  capture  method),  and  work  well 
with fragmented DNA. 
There  are  several FDA-approved liquid  biopsy  assays  in  ad-
vanced-stage lung cancer while there are no approved assays 
for  early-stage  (loco-regional)  disease.  The  FDA-approved 
assays  are  the  cobas®  EGFR  Mutaon  Test  v2  (single-gene 
test,  approved  in  June  2016)
4
,  as  well  as  the  Guardant360 
CDx and FoundaonOne Liquid CDx assays (both NGS based, 
approved  in  August  and  November  2020,  respecvely)
5,6
. 
Liquid  biopsy  tesng  is  also  performed  using  laboratory-
developed-validated assays. These liquid biopsy assays have 
shown a good correlaon with matched ssue-based tesng 
results  (i.e. 81.3%  concordance  in  a  study  of  128  tumors)
7
. 
On the other hand, results in early-stage non-small cell lung 
cancer  have  shown  poor  correlaon  with  ssue-based 
tesng
8,9
  even  though  the  frequency  of  targetable  driver 
mutaons appears to be similar at diagnosis across all stages 
(i.e. a study of lung adenocarcinoma showed that the preva-
lence of EGFR mutaons ranged between 22-26% in stage I-
IV tumors)
10
. A recent study of 197 tumors showed concord-
ance  between  matched  plasma  and  ssue  samples  to  be 
12.4%  in  stage  I,  58.3%  in  stage  II,  55.6%  in  stage  III,  and 
73.8% in stage IV disease
11
. The cause for this discrepancy is 
likely due to dierences in tumor cell shedding, proliferave 
acvity, and the extent of tumor necrosis. 
Studies have also shown that liquid biopsy assays can iden-
fy circulang  ctDNA  in subclinical  disease parcularly when 
monitoring  for  disease  progression  or  therapeuc  eect. 
Numerous  studies have also  been  published  demonstrang 
that liquid biopsy can detect ctDNA in other body uids in-
cluding  pleural  uids,  CSF  (especially  in  cases  with  lep-
tomeningeal  involvement),  as  well  as  uid-based  specimen 
preparaons  like  bronchoalveolar  lavage  or  aspirate  super-
natant.
12-14
  
Liquid  biopsy  is  increasingly  being  used  in  clinical  pracce 
primarily  in  paents  with  stage  IV  disease who  have  no  or 
insucient tumor ssue for tesng. The availability and ease 
of  collecon  of  blood  samples  make  plasma-based  tesng 
very  aracve  for  oncologists,  parcularly  in  high-risk  pa-

Technology Corner

Cone beam CT Applicaons for Bronchoscopy

Introducon

Cone beam CT (CBCT) imaging is a relavely new modality in intervenonal pulmonology, but is a frequently used technology sup-

porng intervenonal radiology and/or cardiovascular procedures. As such, it is oen a readily available system in most centers. It

is furthermore likely that these systems have considerable downme [1] as only one or two speciales are performing specialized

procedures using the CBCT which, in some instuons, oers the opportunity for the intervenonal pulmonologists to use it.

Background

The term cone beam CT refers to the fact that the systems allow for a 3D X-ray projecon by rotang a C-arm with a cone-like di-

verging X-ray beam around the paent in several seconds. This is dierent than that of convenonal CT, where it is foremostly a

narrow fan-like beam of X-rays rotated in helical fashion around the paent with high speed. While this gives addional challenges

from a technological perspecve, it allows for unique addional features too. The xed C-arm of the CBCT arm leaves a lot of open

space as working area and is registered with the table on which the paent is posioned. Once an inial CBCT scan has given 3D

informaon, a digital work staon in the room can subsequently be used to segment certain regions of interest or pathways there-

to. Aer segmentaon, subsequent ‘normal uoroscopy’ 2D imaging within the room is enhanced with the projecon of the seg-

mented volume and/or pathway. This overlay, called augmented uoroscopy (AF), is then accurately maintained in 3D during every

movement of the C-arm and table, and can be used to navigate towards the lesion.

Clinical applicaon

When aempng to biopsy small peripheral nodules, cone beam CT guided navigaon can be used to navigate towards, and subse-

quently biopsy the target lesion. Although mulple dierent modalies are available for navigaon, cone beam CT systems oers

addional value since it can accurately conrm target access in 3D. This conrmaon is vital for opmal diagnosc sampling, deliv-

er markers, and local therapeuc procedures.

How we do it

Our current navigaon bronchoscopy program is based upon the therapeuc bronchoscope and catheters in combinaon with

CBCT and rEBUS under general anesthesia. Aer an inial inspecon bronchoscopy, commercially available steerable navigaon

catheters (e.g. from electromagnec navigaon systems) are inserted. Aer inspecon, a rst quick aempt is made to insert the

catheter according to the pathway as memorized on pre-procedural CT. The scope is xated above the paent. The radiaon tech-

nician checks if a full collision free C-arm rotaon can be made. Everyone leaves the room and an inial 3D CBCT acquision is

made in breath-hold. Both the target nodule and the route toward this nodule are segmented and overlayed as augmented uor-

oscopy imaging (AF) on the dedicated workstaon. For enabling navigaon, small ‘dots’ are placed at the bifurcaons along the

route to highlight the route and addionally show where correct angulaon is most important (Figure 1). Subsequent augmented

W A B I P N E W S L E T T E R

P A G E 4

Erik van der Heijden, MD

PhD

Associate Professor

Intervenonal

Pulmonology,

Radboud University

Medical Center

Nijmegen, The

Netherlands

Stephan Kops, MD

Resident

Intervenonal

Pulmonology,

Radboud University

Medical Center

Nijmegen, The

Netherlands

Roel Verhoeven, MSc

Technical Medicine

Specialist

Intervenonal

Pulmonology,

Radboud University

Medical Center

Nijmegen, The

Netherlands

uoroscopy imaging can now be performed with dierent C-arm angulaons, having the overlayed route and lesion to conrm reposion-

ing or progression. When the target lesion is close, radial EBUS miniprobes and 3D-image conrmaon with a new CBCT acquision are

used to conrm lesion access. If needed, reposioning is performed under addional image guidance. Aer lesion access conrmaon, s-

sue sampling is repeatedly performed under guidance of AF and repeated rEBUS. Sampling is performed under AF at mulple angulaons

and small, constant adjustments of the catheter rotaon and posion.

We frequently perform 2 CBCT scans (of dierent dose) per lesion. Depending on system sengs, paent characteriscs and the amount of

collimaon used, an inial ‘high quality’ CBCT acquision will result in a paent dose of approximately 2-4 mSv. Total procedural

(augmented) uoroscopy dose is highly dependent on how specic and sparsely it is used. As an example, at the start of our program the

procedural uoroscopy paent dose was 5.2 mSv (592 seconds). In an experienced seng (i.e >100 procedures), we however reduced to a

mean of 0.37 mSv per procedure (935 seconds). Knowing the sta should leave the room during CBCT acquision and wear adequate pro-

tecon and systemacally put a mobile safety screen in between themselves and the c-arm, the sta dose seems to be of a lesser concern.

Accuracy

Several studies have reported on their accuracy ndings when using CBCT in addion with other guidance techniques, reaching diagnosc

yields of 70-84% [2]. Combining above menoned workup with EMN in approximately half of procedures, our inial report found an overall

diagnosc accuracy of 72% in 87 paents [3]. Importantly however, analysis of our program aer having performed more than 150 proce-

dures shows the changing performance over me. In a more recent series (Nov 2019 – June 2020) of 64 paents, an accurate diagnosis

without changing inclusion criteria could be obtained in some 90% of paents [4]. This is a signicant improvement over our own and other

previously reported accuracies with commercially available technology. However, our analysis of more than 200 consecuvely CBCT guided

navigaon bronchoscopy cases also shows that there is an important learning curve to overcome [3, 4].

Conclusion

Cone beam CT guided navigaon bronchoscopy is a valuable opon to navigate to, and obtain a ssue diagnosis in small, peripheral pulmo-

nary nodules, and is likely a prerequisite to precisely deliver minimal invasive treatments. The limited data available seem to imply it has

the potenal of a high diagnosc accuracy, outperforming other technologies, but it is important to note there is a signicant learning

curve to overcome. The radiaon dose needed is (relavely) low. Further research is warranted to improve the ‘intuiveness’ to use this

guidance tool as well as improvement of our sampling tools to reduce procedure me.

W A B I P N E W S L E T T E R P A G E 5

References

1. Patel S et al. Int J Health Policy Manag, 2020.

2. Casal R.F. J Bronchology Interv Pulmonol, 2018. 25(4): p. 255-256.

3. Verhoeven R.L.J et al. J Bronchology Interv Pulmonol, 2021. 28(1):

p. 60-69.

4. Verhoeven R.L.J et al. Cone-beam CT and augmented uoroscopy

guided navigaon bronchoscopy; radiaon exposure and diagnosc

accuracy learning curves. Submied, 2021.

Figure 1:

On the le: CBCT-based navigaon bronchoscopy in pro-

gress. On the right, top: two images of the workstaon for

segmentaon. On the right, boom: augmented uoroscopy

image of the extended working channel with the radial EBUS

miniprobe being inserted into the target lesion (in blue-

green). The red dots indicate the navigaon route.

Tips from the Experts

P A G E 6 V O L U M E 9 , I S S U E 2

Introducon

More than 50% of paents with malignant pleural eusion (MPE) reaccumulate uid aer the inial drainage, with up to 30% of paents

developing rapid re-accumulaon within two weeks [1,2]. Guidelines from professional sociees recommend that paents who are sympto-

mac with recurrent suspected or known MPE should undergo denive pleural intervenons [3-5]. These intervenons include talc pleu-

rodesis with or without thoracoscopy, and tunneled indwelling pleural catheter (TIPC) placement. These procedures result in fewer subse-

quent pleural procedures and complicaons such as pneumothorax and complex pleural space [1]. Despite the high incidence of MPE,

guideline consistent care of providing denive pleural intervenon is followed in less than 25% of paents [1]. Here, we aim to provide a

raonale for selecng the appropriate denive pleural intervenon for managing paents with recurrent MPE.

Indicaons, planning and techniques for specic pleural intervenons

1. Talc Pleurodesis with Insuaon or Slurry

In paents with recurrent symptomac MPE who experience relief of their dyspnea with uid drainage and have a complete or parally ex-

pandable lung, achieving pleurodesis can minimize pleural uid reaccumulaon. This can be achieved via chemical pleurodesis by inslling a

sclerosant, such as talc, into the pleural space. Talc pleurodesis can be performed by inslling talc slurry via a chest tube or by insuaon

during thoracoscopy by applying a spray atomizer. This can be performed using a dedicated catheter either through the trocar adjacent to

the rigid pleuroscope or a catheter inserted through the working channel of a semi-rigid pleuroscope. In both cases, talc insuaon can be

applied under direct visualizaon, maximizing the distribuon of the talc on the desired surfaces, which should include normal parietal pleu-

ra (Figures 1A,1B).

There is mixed data regarding the opmal method for talc delivery. Several randomized trials, systemac reviews, and meta-analysis suggest

no overall dierence between thoracoscopic talc insuaon and bedside talc slurry via chest tube in regard to pleurodesis success, compli-

caons, clinical outcome, or recurrence of pleural eusion [6-10]. That being said, pleurodesis success rate using thoracoscopic talc insua-

on for MPE has been reported as high as 77-98% [11-16]. One systemac review suggested that talc insuaon was associated with less

risk of recurrence than talc slurry via chest tube [17]. In addion, in a post-hoc analysis, Dresler et al. showed that paents with primary lung

or breast cancer were noted to have higher rate of pleurodesis with talc insuaon compared to talc slurry via chest tube (82% vs 67%) [8].

Terra et al. noted that immediate paral lung expansion was more frequently seen in paents who received thoracoscopy with talc insua-

on as opposed to talc slurry via chest tube (60% vs 30%) [9]. Whether this translates to improved clinical outcomes is unclear.

The decision to proceed with either talc insuaon or talc slurry depends on the local resources, operator experience, paent risk factors,

and paent values. In our instuon, paents with relavely good performance status (ECOG 0-2) and someme ECOG 3, are oered both

Indwelling Catheters and Pleurodesis for Managing Recurrent Malignant Pleural

Eusion

Sepmiu Murgu, MD

The University of Chicago

Elliot Ho, DO

The University of Chicago

Tips from the Experts

P A G E 7 V O L U M E 9 , I S S U E 2

thoracoscopic talc insuaon and TIPC. Paents with poor performance status (ECOG 3-4) at high risk for anesthesia, are usually managed

with TIPC. We do not rounely place a chest tube for talc slurry in these paents, but if paents already have an indwelling chest tube, then

talc slurry via the exisng chest tube is performed.

2. Tunneled Indwelling Pleural Catheter Placement

While paral or complete re-expandable lung is needed for chemical pleurodesis, TIPC placement is the treatment of choice for paents with

non-expandable lung, or those who failed chemical pleurodesis. This is relevant, especially since some data suggest that approximately 30%

of paents with MPE have non-expandable lung [8]. The major disadvantages are the need for frequent drainage (someme considered by

paents an intervenon per se), the need for clinic appointments to troubleshoot catheter occlusion and management of catheter-related

skin infecon, as well as lifestyle modicaons that have to account for me to drain the catheter on a regular basis (every day per some pro-

tocols) and avoiding soaking the catheter in water (e.g. pool, bathtub). Regardless of lung expandability, several guidelines suggest that TIPC

placement is just as eecve as talc pleurodesis in relieving symptoms of dyspnea and improving quality of life in paents with recurrent MPE

[2-4]. Two landmark studies (TIME2 and AMPLE) showed no dierence in the relief of dyspnea between TIPC placement and talc pleurodesis,

however showed reduced length of hospital stay and need for subsequent pleural procedures in paents who received TIPC placement

[18,19].

TIPC can be placed either under local anesthesia at the bedside (or procedure suite) with ultrasound guidance or via thoracoscopy under di-

rect visualizaon (Figures 1C,1D). In both cases, the indwelling catheter should be guided towards the diaphragmac recess to facilitate com-

plete evacuaon of the pleural uid. Although pleurodesis is not necessarily the goal for TIPC placement, spontaneous pleurodesis has been

reported in 30-58% of paents who undergo TIPC placement [19-23]. This may be the result of keeping the pleural space dry with daily drain-

age allowing for approximaon of the pleural surfaces, and the inammatory response caused by the presence of the indwelling catheter in

the pleural space. We have also noted spontaneous pleurodesis in some paents with non-expandable lung on inial evaluaon. This may be

due to shiing of thoracic structures within the chest cavity (ipsilateral mediasnal shi, elevaon of the hemidiaphragm) as a result of daily

drainage of pleural uid resulng in the approximaon of pleural surfaces, lack of drainage, and subsequent catheter removal.

In our opinion, a meaningful dialogue with paents and their caregivers is in order prior to inserng a TIPC that may be needed for months

(median me to TIPC removal: 44-90 days), if not for the rest of the paent’s life [20,24]. Correct expectaons should be set in regard to fre-

quency of drainage, chance of catheter removal, possibility of uid recurrence aer catheter removal (4-14%) [24], and potenal TIPC-related

complicaons and their management (including occlusion and infecon).

3. Thoracoscopy: Stand Alone, with TIPC Placement, Talc Insuaon or a Mulmodal Approach

Thoracoscopy can be performed either under moderate sedaon or general anesthesia. In our pracce, thoracoscopy is performed in the

operang room with the paent under general anesthesia. Double lumen intubaon is used to permit single lung venlaon during the pro-

cedure. This allows for deaon and isolaon of the target pleural space, giving the operator maximal pleural cavity to work with during the

procedure. We rounely use ultrasound guidance not only to conrm that the lung has been properly isolated (US reveals pneumothorax

paern at the desired point of entry), but also to dene the complexity of the pleural space, which may predict the need for a more complex

intervenon, rather than a single port thoracoscopy. Once the trocar is inserted, either rigid or semi-rigid pleuroscope is used for drainage,

exploraon of the pleural cavity, and to obtain pleural biopsies, if needed for ssue diagnosis or ancillary studies (molecular tesng, PD-L1

tesng, etc.).

Even though thoracoscopy is oen used in conjuncon with either TIPC placement or talc pleurodesis, the ability to induce pleurodesis may

also be intrinsic to thoracoscopy. Suzuki et al. noted that spontaneous pleurodesis occurred in 53% of paents who underwent thoracoscopic

placement of TIPC as compared with 28% of paents who underwent TIPC placement via standard technique [25]. Another study demon-

strated spontaneous pleurodesis rate of 58% in paents with trapped lung undergoing TIPC placement via thoracoscopy [26]. This may be the

result of completely drying out the pleural space under direct visualizaon, mechanical irritaon of the pleural space from thoracoscopy inci-

sion and pleural biopsies leading to an inammatory response, and the ability to perform adhesiolysis in paents with loculated eusions.

There is increasing interest in combining the use of TIPC placement with talc insuaon in paents undergoing thoracoscopy during the

same procedure in order to improve the likelihood of pleurodesis and reduce the me to catheter removal. We rounely apply this approach.

We believe that in addion to the intrinsic ability of thoracoscopy to induce pleurodesis, direct visualizaon under thoracoscopy allows for

directed applicaon of talc insuaon across the pleural surfaces and guidance of the TIPC placement towards the diaphragmac recess. The

data supporng this pracce is limited, but emerging. In a pilot study, the combinaon of thoracoscopy with talc insuaon and TIPC place-

Tips from the Experts

P A G E 8 V O L U M E 9 , I S S U E 2

ment in the same procedure resulted in high pleurodesis success of 92% and early TIPC removal, with median duraon of TIPC of 7.54 days

post-intervenon, and median length of hospital stay of 1.79 days [27]. Similarly, in a prospecve observaonal study, the combinaon of

thoracoscopy with talc pleurodesis and TIPC placement also resulted in high pleurodesis success of 92% at 1 month, 96% at 6 months, and

early TIPC removal, with median duraon of TIPC of 6 days post-intervenon, and median length of hospital stay of 3 days [28]. Therefore, we

believe that when discussing with paents the opons for more denive pleural intervenons for their recurrent and symptomac MPE, it is

important to assess their values and evaluate whether the benets of early TIPC removal seen with thoracoscopic TIPC placement, outweighs

the risks of thoracoscopy and the costs of post-procedural hospitalizaon. In addion, hospitalizaon is not always necessary; in fact, some

operators apply a rapid pleurodesis protocol, which involves discharging paents 24-hours aer combined thoracoscopy with TIPC placement

and talc pleurodesis, with connued home TIPC drainage [27]. In paents with concurrent need for pleural biopsies, complex pleural eu-

sions, or unwillingness to have a long-term TIPC, a mulmodal approach should be considered given the possibility for early TIPC removal.

Quality Control: Post-procedural Management

Hospitalizaon

TIPC placement with local anesthesia can be performed on an outpaent basis and does not require hospitalizaon. However, with thoraco-

scopic TIPC placement and talc pleurodesis, there is a subsequent increased inammatory response in the pleural space usually leading to

pain and increased pleural drainage. In our pracce, in addion to the TIPC, a 24-28Fr chest tube is placed during thoracoscopy in order to

allow for connuous drainage to keep the pleural space as dry as possible to opmize the eects of talc pleurodesis. We typically keep pa-

ents hospitalized for 1-3 days unl the pleural uid drainage is minimal (<100-150 cc) and to allow for opmizing pain control and connu-

ous pleural drainage [29]. An alternave approach, using rapid pleurodesis concept, involves discharging paents 24-hours aer combined

thoracoscopy with TIPC placement and talc pleurodesis, with connued home TIPC drainage (three mes daily on post-op day 1, two mes

daily on post-op day 2-3, and then daily) [27]. Randomized trials have not been performed comparing the two approaches in regard to pleu-

rodesis success, symptomac improvement and need for repeat intervenons.

Drainage Protocol

The ASAP and AMPLE2 trials evaluated daily TIPC drainage as compared with alternate day drainage and symptom-based drainage, respec-

vely, and demonstrated higher rates of spontaneous pleurodesis in paents who drained daily [20,21]. Although, there was no signicant

dierence in dyspnea control between the two groups, the higher rates of spontaneous pleurodesis in paents who drained daily may trans-

late to early TIPC removal. In our pracce, we recommend daily drainage unl drainage is less than 150 cc daily on three occasions, which is

then extended to every other day drainage. Once drainage is less than 150 cc on three occasions, drainage is extended to every three days. If

drainage is sll less than 150 cc on three occasions, we evaluate paents at that me for TIPC removal.

Follow-Up

Post-procedural care is oen instuonal and resource dependent. At our instuon, we evaluate paents in clinic two weeks aer the pro-

cedure or sooner if needed with repeat chest imaging and suture removal on the day of clinic visit. There is emerging evidence that TIPC re-

moval is someme performed at the me of disease control, not because of pleurodesis. In fact, we rounely perform thoracic US at the me

of TIPC removal with the intent to predict which paents are more likely to recur aer catheter removal based on sonographic ndings of

lung sliding or to document possible pleurodesis by visualizing the lack of lung sliding [24].

Conclusion

Pleural intervenons for palliang symptoms due to MPE are recommended for paents with recurrent symptomac MPE who experience

relief of their dyspnea with uid drainage. Decision to select the appropriate intervenon should be individualized based on local resources,

operator experience, paent’s comorbidies, funconal status, and values. A mulmodal approach including thoracoscopy with talc pleu-

rodesis and TIPC placement as a more denive pleural management may fasten the me to pleurodesis, allowing for early TIPC removal.

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P A G E 9 V O L U M E 9 , I S S U E 2

References

1. Ost DE et al. Chest. 2018 Feb;153(2):438-452.

2. Grosu HB et al. Respirology. 2019 Jan;24(1):76-82.

3. Feller-Kopman DJ et al. Am J Respir Crit Care Med. 2018 Oct 1;198(7):839-849.

4. Bibby AC et al. Eur Respir J. 2018 Jul 27;52(1):1800349.

5. Planchard D et al. Ann Oncol. 2019 May;30(5):863-870.

6. Yim AP et al. Ann Thorac Surg. 1996 Dec;62(6):1655-8.

7. Mummadi S et al. F1000Res. 2014 Oct 27;3:254.

8. Dresler CM et al. Chest. 2005 Mar;127(3):909-15.

9. Terra RM et al. Chest. 2009 Aug;136(2):361-368.

10. Bhatnagar R et al. JAMA. 2019 Dec 5;323(1):60–9.

11. Janssen JP et al. Lancet. 2007 May 5;369(9572):1535-1539.

12. Viallat JR et al. Chest. 1996 Dec;110(6):1387-93.

13. de Campos JR et al. Chest. 2001 Mar;119(3):801-6.

14. Kolschmann S et al. Chest. 2005 Sep;128(3):1431-5.

15. Steger V et al. Ann Thorac Surg. 2007 Jun;83(6):1940-5.

16. Barbetakis N et al. J Cardiothorac Surg. 2010 Apr 19;5:27.

17. Tan C et al. Eur J Cardiothorac Surg. 2006 May;29(5):829-38.

18. Davies HE et al. JAMA. 2012 Jun 13;307(22):2383-9.

19. Thomas R et al. JAMA. 2017 Nov 21;318(19):1903-1912.

20. Wahidi MM et al. Am J Respir Crit Care Med. 2017 Apr 15;195(8):1050-1057.

21. Muruganandan S et al. Lancet Respir Med. 2018 Sep;6(9):671-680.

22. Tremblay A et al. Chest. 2006 Feb;129(2):362-368.

23. Warren WH et al. Ann Thorac Surg. 2008 Mar;85(3):1049-55.

24. Chaddha U et al. Respirology. 2021 Mar;26(3):249-254.

25. Suzuki K et al. J Thorac Oncol. 2011 Apr;6(4):762-7.

26. Schneider T et al. Thorac Cardiovasc Surg. 2009 Feb;57(1):42-6.

27. Reddy C et al. Chest. 2011 Jun;139(6):1419-1423.

28. Boujaoude Z et al. J Bronchology Interv Pulmonol. 2015 Jul;22(3):237-43.

29. Lee P et al. Respirology. 2007 Nov;12(6):881-6.

Figure 1: (A) Talc insuaon applied with thoraco-

scopic guidance. (B) Talc powder is distributed homog-

enously over the parietal pleura. (C) Dilator and guide-

wire are oriented towards the diaphragmac recess

during TIPC placement under direct visualizaon. (D)

Successful TIPC placement with thoracoscopic guid-

ance.

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W A B I P N E W S L E T T E R P A G E 10

Ethical Issues of Immunity Passports

Since the beginning of the pandemic, strict lockdown measures have been imposed in most of the countries in order to re-

duce the spread of the coronavirus. Social distancing, home working, only virtual acvies for school, university and academ-

ic convenons were implemented in dierent mes and with dierent length as well as mask wearing and home quarann-

ing. Some of these measures had very signicant social and economic costs, mainly by prevenng many people from work-

ing. The main reason that has obliged to lockdown measures (increasingly unpopular because of their economic impact) is

the potenal for asymptomac infecon and spreading of COVID-19. People who do not experience symptoms when infect-

ed with COVID-19 is esmated to be around 40% and there is evidence that support the hypothesis that a large proporon

of the transmission of the virus occurs before the onset of symptoms, making necessary to have ways of prevenng of

spreading of the disease from asymptomac persons.

Most of governments do not consider mandatory vaccinaon as an acceptable strategy. But more recently, taking into ac-

count the new waves, new variants, increasing pressures to return to free circulaon of people, many governments are con-

sidering some sort of immunity passports. Those cercates would allow people with proof of immunity (because of having

suered the disease and/or having received full vaccinaon) to have more freedom of circulaon. But those proposals raise

many logiscal and ethical concerns as people without that cercaon will be excluded from everyday life.

The main purpose of vaccine passports is to allow people to travel, aend large gatherings, access public venues, and return

to work without compromising personal safety and public health. The UK government recently announced that it is being

analysed whether Britons will need a vaccinaon test or a negave Covid-19 test to visit bars, return to the oce, or aend

theaters and sporng events. Dierent countries are considering dierent acvies that would be permied for holders of

those immunity passports but not to other people.

In Israel, a vaccine passport allows those vaccinated to go to hotels and gyms while Iceland is distribung vaccine passports

to facilitate travel abroad for the vaccinated. In the US government, some agencies are evaluang the feasibility of creang

digital Covid-19 vaccinaon cercates. New York’s “Excelsior Pass” permits aendance at theaters, arenas, event venues,

and large weddings and European Union plans a “Digital Green Cercate” that would allow free travel within the EU

Beyond dierent government intenons, it is prey certain that proof of vaccinaon against COVID-19 may soon be a re-

quirement for airline or cruise ship passengers. Some companies—like Qantas Airlines and the American Queen Steamboat

Company—have announced that they will soon require “immunity passports,” to use their services and some employers may

soon mandate vaccinaons as well.

Many tech companies, are working around the clock to provide the technology required for digital immunity passports, pre-

dicng that they will be widely used in the near future and many countries see they will need to develop those passport if

they are requested by other countries in order to be able to ensure alignment with global standards.

But in spite of this rapid progress to the acceptability of the idea of the implementaon of those cercates, there are sll

many scienc challenges and the discussion about if they are lawful and ethical Is not closed yet.

Immunity passports would a way to go back to a more normal social and economic life, but their potenal benets will be

unequally distributed, giving rise to doubt about how ethical their implementaon will be.

On the one hand, immunity passports oer an opportunity for employees to go back to work and families to reunite. On the

other hand, they will not be available to everyone, and they will exacerbate exisng inequalies.

An inial disncon should be established between “immunity passports” (those given to those who have suered the dis-

ease and have proof of circulang anbodies) and the “vaccinaon passports” (applied only to those who have received a

full vaccinaon).

As the COVID-19 pandemic progresses, many people worldwide will contract the virus and recover. Many of these will be

asymptomac or experience mild symptoms only. Whether all illness results in sucient levels of neutralising anbodies to

prevent against reinfecon is sll under invesgaon. Although experience with diseases like severe acute respiratory syn-

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W A B I P N E W S L E T T E R P A G E 11

drome (SARS) and Middle East respiratory syndrome (MERS) suggests that anbody responses are likely to persist for at least

a year it is not fully established yet what level of immunity is conferred by infecon. It is reasonable (although not proved) to

believe that people who have been infected and subsequently recovered are likely to be at least temporarily at lower risk of

reinfecon or severe disease and less likely to spread the virus to other people. But the extent and duraon of immunity

infecon from COVID-19 is uncertain and the WHO has repeatedly stated that there is no evidence of lasng immunity in

those recovered from COVID-19. In fact that evidence would be to wait very long aer infecon and test the immunity in

recovered paents to conrm the prevalence of anbodies at 1, 5, 10 or more years.

If anbody responses to COVID as in SARS and MERS are waned aer 2–3 years, immune passports should be me limited. A

signicant limitaon on the introducon of immunity passports is the need for a suciently reliable rapid test for COVID-19

anbodies. Anbody, or serology, tests idenfy whether someone has developed anbodies to COVID-19. Assuming that

anbodies do indicate solid immunity, the challenge lies in correctly idenfying those anbodies in a way that permits

tesng to be scaled up signicantly, without exceeding a tolerable level of false posives/negaves.

Dierent tests vary in their accuracy and the quality of the evidence we have about their accuracy. The sensivity of tests in

the rst week or two aer infecon may be low. An addional problem is that the numbers of false posive and false nega-

ve tests (and so the impact those errors have) will depend on the baseline rates of infecon. If the rates of seroposivity

are low, many of those idened as being immune will be false posives. On the other hand, anbodies might not be iden-

able in blood tests unl days or weeks aer illness has resolved, resulng in a delay between an individual being infected

with COVID-19 and being tested seroposive.

Widespread anbody tesng could facilitate a faster return to a more normal way of life for at least some of the populaon.

But it could also create new pressures to intrude on people’s privacy and free choice. Employers may want all their employ-

ees to undergo tesng creang pressure on people into tesng in this manner.

The feasibility of being tested (and consequently have the possibility of having proof of immunity) requires the consideraon

of who should be priorized for tesng, not only taking into account the cost and logisc burden of over tesng but also the

need to avoid harmful misdiagnoses. It is likely that tesng will be priorized to healthcare sta and other key workers as

care home sta, police, supermarket sta, transport workers and some others that need to keep on working to permit social

funconing. It means that those populaons would receive the privilege of having access to tests and consequently proof of

immunity. It would not necessarily be unfair. The public good that those workers mean if they are allowed to move around

more freely, juses their posion of privilege for anbody tesng and immunity passports. But if immunity passports were

to be introduced, it is unclear how other groups should be priorized relave to one another to not create an unfair inequali-

ty of access to restricted acvies as it is likely that possessing an immunity passport would be a signicant benet, ad-

vantaging holders relave to non-holders.

As fairness requires all people to be treated the same in a strict sense, this would indeed be the case. But it is also true that

such a simplisc model of fairness is not appropriate in the current extraordinary condions and that privileging fairness

above other values (such as benets to individual well-being and economic recovery) is not necessarily a moral imperave.

The more people that are able to return to some of their normal funconing, the beer for society as a whole. On the other

hand, there is a risk of resentment from those unable to work or socialize due to their connued suscepbility. This could

result in a reducon in social cohesion and a loss of support of restricon measures, which could have a negave impact in

the longer term management of the pandemic. There might also be some concerns that those most likely to acquire immuni-

ty (and thus, immunity passports) are those who have been least responsible in following government guidelines while

those who strictly respected social distancing are the least likely to acquire immunity and immunity passports. It would

mean that immunity passports could reward the least responsible or even incenvize incauous behavior (as intenonal

exposure to the virus), in order to acquire an immunity passport ‘legimately’ . It would undermine the eorts of containing

spread of the virus.

Successfully avoid geng COVID-19 should be enough advantage for those who behave conscienously, but it would sll be

unfair. To avoid that, governments should withhold immunity passports from those who acquire immunity through reckless

behaviour. It would require public educaon campaigns that make people aware that if they are caught violang the rules,

they will be ineligible for immunity passports. But, it will be dicult to determine retrospecvely whether an individual with

immunity acquired it through incauous behavior or not.

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W A B I P N E W S L E T T E R P A G E 12

In order to prevent the creaon of fraudulent immunity passports, systems of vericaon will be needed. A higher invest-

ment in technology would be necessary for the passports be harder to forge and punishments should be applied for those

involved in the black market of passports. All that machinery would largely decrease the economic benets of immunity

passports.

Taking into account all the challenging issues, especially the many ethical quesons but mainly the enormous scienc un-

certainty to support the use of immunity cercaon for those having suered the disease and showing proof of having an-

bodies, have not been widely accepted.

But with the availability of vaccinaon the idea of using cercaon of immunity, but restricted to immunity conferred by

vaccines, has re-emerged with force, as there is more scienc evidence for immunity from vaccines than from natural im-

munity.

However, even when the scienc foundaons are stronger and some logisc issues are easier to resolve, vaccinaon pass-

ports sll have their own ethical challenges. It could discriminate against minority communies, against people less eligible

or less likely to accept the vaccines, against those less likely to be given priority to receive them. And of course, globally

against people residing in countries with less access to vaccines. There are also big quesons about the ethics of granng

businesses access to peoples’ health records. In the current world of media technology corporaons the risk of big compa-

nies having access to private informaon and commercialize it or merge it with other informaon and then use it for their

advantage, is a concrete and real threat.

The project turns vaccinaon, if not mandatory, into almost compulsory in order to access to highly desirable acvies. For

instance, while vaccinaon in Israel is not mandated, parliament passed a law that would allow the Ministry of Health to

idenfy unvaccinated people and nofy them to the authories.

Because of the discriminaon that the cercates potenally impose, some opinions queson if those passports are even

lawful.

Proof of immunizaon is far from being a new idea; during campaigns for the smallpox vaccine, the vaccine scar oen served

as this proof and gave access to acvies as train travel. Many countries require proof of immunizaon for school entry and

in most of the countries health care workers are required to present proof of vaccinaon against hepas B. The Equal Em-

ployment Opportunity Commission in the US allows employers to require SARS-CoV-2 vaccinaon to return to the work-

place, thus ensuring employees do “not pose a direct threat to health or safety. If employees are not required to provide any

medical addional informaon as part of the proof, employers could require vaccinaon passports as proof their sta have

received a COVID-19 vaccinaon.

In fact, vaccine passports are not only permissible under internaonal health regulaons, but also they already exist. The

World Health Organizaon endorses cercates conrming vaccinaon against yellow fever for entry into countries where

the disease is endemic. Governments have power to validate and monitor vaccinaon status while requiring proof of vac-

cinaon for access to certain privileges. Internaonal law poses few restricons on vaccinaon cercaons. The Interna-

onal Health Regulaons, signed by 196 countries, grant wide discreon to exercise evidence-based public health powers. It

is the Arcle 31 of these regulaons which specically allows governments to require “proof of vaccinaon or other prophy-

laxis,” while Annex 7 authorizes yellow fever vaccinaon cercates for internaonal travel.

Opposite to immunity passports, which has the risk of incenvizing infecon, vaccine passports incenvize vaccinaon,

which is a posive benet and contributes to the whole populaon immunity.

It is also in accordance with the public health principle of least infringement that dictates that policy makers should imple-

ment the opon that least impairs individual liberes in order to achieve a common good. Lockdowns may be required in

order to decrease the number of cases and deaths, even when it is one of the major restricon of the civil liberes. Vaccine

passports could provide more freedom of movements for those with minimal risk of geng and spreading the disease and

help prevent other health and socioeconomic harms caused by lockdowns.

Ethical concerns about these passports are not resolved at all. The Nueld Council on Bioethics states that such passports

could enable coercive and sgmazing workplaces. Vaccine passports should be available and accessible to all countries and

to all populaons in each country. Otherwise they risk to increase the already exisng societal inequalies and worsening

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W A B I P N E W S L E T T E R P A G E 13

the health inequality. But that is not and easily achievable goal. Vaccines are scarce and access remains deeply unequal, both

globally and within countries. People facing vaccinaon access problems will be unable to obtain vaccine passports.

Even with a more fair access to vaccines, some groups are excluded from vaccinaon for medical reasons, cultural beliefs or

religious convicons.Covid-19 vaccines are contraindicated in some people with serious health condions and allergies and

pregnant women do not have evidence (as clinical trials did not include pregnant women) about the safety of vaccinaon

and may choose not to take that risk. In some countries, ethnic minories are also more likely to be vaccine hesitant, poli-

cal inclinaons may determine higher distrust in the vaccines and younger people, not being a priorized group, will take

much longer to be vaccinated as well as believing less vulnerable to severe disease, may be less inclined to get the vaccines.

But the most obscene inequality is that most vaccine doses are being delivered in high income countries, WHO warned that

the world is facing a catastrophic moral failure represented by the insucient eorts to support globally coordinated access

to covid-19 vaccines. It is esmated that nearly 25% of the world’s populaon will not have access to any COVID vaccine unl

2022, resulng in thousands of preventable deaths in less developed countries. Far from the inial dream that this global

crisis would improve the understanding of the urgent need of decreasing the unacceptable inequity between poor and rich

countries and poor and rich individuals, in most of the countries the pandemic is widening those dierences. Requiring proof

of vaccinaon mainly to be able to travel, will deepen the inequality and exclusion of the low income countries compared to

the high income countries.

Only when everyone can gain access to vaccines, there would be a strong ethical juscaon for vaccine passports in order

to create safer environments to work, shop, socialize, and travel, that could be preferable as a less restricve alternave to

lockdown measures. It means that if wanng to enjoy the potenal benets of vaccine passports without paying an unac-

ceptable moral price of unfairness and discriminaon, every country should contribute to the global eort in order to in-

crease access to vaccinaon, both globally and within countries. By denion, a pandemic is a global problem and must be

faced globally. Beyond any ethical concern, a world with less than half of the world’s populaon vaccinated will not be safe

for anyone.

If vaccines are fully and equally available to all members of society, including the most disadvantaged people, and in that

way, not taking the vaccine is a personal choice, it would be possible to argue that unvaccinated individuals have no right to

impose risks on others, thus impeding a return to normal acvies. Requiring people who decline vaccinaon to bear some

consequence for their refusal seems only fair, especially if, collecvely, such hesitancy puts herd immunity out of reach. In

that scenario, individuals who cannot be vaccinated for medical reasons should not be excluded from passport privileges and

granng exempons for genuine religious or conscienous objecons should be considered.

In the same way that the previously planned immunity passports, technical challenges are not resolved. Mechanisms for

reliable and accurate cercaon are important. The development of such mechanisms is a technical issue that sooner than

later some leading technology companies should be able to answer successfully. As vaccine passports would probably be

digital and require access to private medical records, there are important quesons around internet access, costs of acquir-

ing and maintaining the passports, privacy, and data protecon that must be carefully studied. In some countries a large pro-

poron of the populaon do not have smartphones or stable internet connecons and their exclusion would breach their

rights to equality. Allowing workplaces, airlines, and entertainment and leisure venues to access to vaccinaon data remains

controversial as it may permit paent sensive data be used for other purposes than the vaccine passports. It could also al-

low immunizaon informaon to be used by private companies like airlines, workplaces or amusement parks to deny entry

with the excuse of keeping people safe and liming the spread of this deadly virus. That would create an addional form of

elism and a deeper societal gap.

A key component of any internaonally valid passport should be that those cercaons need to be internaonally stand-

ardised and must have veriable credenals that prevent problems such as forgery and loss of privacy. Soware, implement-

ed in a standardized fashion, will be required to verify vaccinaon status and to determine whether immunizaon passports

meet current requirements for entry or access. Mechanisms must also exist to revoke passports if, for example, data emerge

that new variants of SARS-CoV-2 are resistant to vaccines. Technological development should occur in concert with legal and

ethical review to ensure that the soluon is the least restricve means of reopening society, without adversely aecng pop-

ulaons that are already marginalized. WHO has iniated a Smart Vaccinaon Cercate Working Group to establish key

specicaons and standards for eecve and interoperable digital soluons for covid-19 vaccinaon. Some instuons have

developed potenal criteria for such passports, for instance, the Royal Society which suggests passports should accommo-

Humanitarian News

W A B I P N E W S L E T T E R P A G E 14

date dierences between vaccines in their ecacy, register changes in vaccine ecacy against emerging variants, be inter-

naonally standardized and have veriable credenal. They should also be based on a plaorm of interoperable technolo-

gies, be secure for personal data, be portable and be aordable to individuals and governments

Taking into account all these consideraons, while the merits of vaccine passports may be undeniable, implementaon will

require ethical juscaons and praccal soluons that do not discriminate against the poor, the less technically literate,

and people from low and middle income countries. The policies to implement those passports will require a exible adapta-

on as we have learnt that pandemic policies that are sensible when launched may need to be rethought a month later.

Without migaon strategies for inequality of access and alternave soluons, the hardships experienced by marginalised

and vulnerable groups will be intensied through the perpetuaon of discriminaon.

The most formidable challenge of this me is to decrease the morally and praccally inadmissible levels of inequity all over

the world. That situaon represents not only a scandalous moral defeat but also a danger for democracy as we have known

it unl now. If not carefully, thoughully and ethically planned, the negave impacts of a cercaon system are likely to fall

disproporonately on those who are already socially marginalised and disadvantaged. Sociees globally must strive to en-

sure that passports are available to all in the most fair manner and with the highest respect for fundamental human rights.

*The views expressed in this arcle are those of the author (Silvia Quadrelli) and do not necessarily reect the ocial posi-

ons of the Execuve Board or Internaonal Board of Regents of the WABIP.

References:

1. Brown RCH et al. J. Med. Ethics. 2020;46:652-659.

2. Gosn LO et al. JAMA. Published online April 07, 2021. doi:10.1001/jama.2021.5283

3. Nueld Council on Bioethics. Rapid policy brieng: covid-19 anbody tesng and “immunity cercaon.”

2020. www.nueldbioethics.org/publicaons/covid-19-anbody-tesng-and-immunity-cercaon.

4. Osama T et al. BMJ. 2021 Apr 1;373:n861. doi: 10.1136/bmj.n861. PMID: 33795260.

5. Royal Society. Twelve criteria for the development and use of covid-19 vaccine passports. 2021. hps://royalsociety.org/-/media/

policy/projects/set-c/set-c-vaccine-passports.pdf.

6. WHO. Interim guidance for developing a Smart Vaccinaon Cercate. hps://cdn.who.int/media/docs/default-source/documents/

interim-guidance-svc_20210319_nal.pdf?sfvrsn=b95db77d_11&download=true (accessed April 1, 2021)

7. WHO "Immunity passports" in the context of COVID-19, 2020. Available: hps://www.who.int/news-room/commentaries/detail/

immunity-passports-in-the-context-of-covid-19 [Accessed 27 Jan 2021].

Best Image Contest 2021 (2 of 3)

Descripon:

(A) Organized blood clot in the RLL

(B) Cryo-extracon of the clot

Submier:

Dr. Syeda Samia Rasheed M.D

Best Image Contest

P A G E 15

This image is 1 of 3 selected among 100+ submissions to our Best Image Contest held in late 2020. Please stay

tuned to the next Image Contest opening later this year! Find the above image and more at the WABIP Acade-

my Image Library at hps://www.WABIPacademy.com/imagelibrary

P A G E 16

WABIP News

Maximising Yield for Molecular Analysis at EBUS TBNA

We are pleased to present to you our new, on-demand webinar

available to all for free. Follow the below buon to watch online.

In part 1 of the video presented by Prof. David Fielding, you will

learn:

• Needle localisaon within nodes including the use of Doppler

• The Importance of Good quality ROSE slides with ps on

preparaon

• Choice of collecon media

In the second part as presented by Prof. Sinchita Roy-Chowdhuri, you will nd:

• Cytology preparaon

• Pre analyc variables

• Cellularity evaluaon

• Specimen enrichment

Upcoming Events

• 8th Indonesian Pediatric Respiratory Meeng in conjuncon with The 3rd Asian Pediatric Intervenonal Pul-

monology Associaon Meeng

When: June 4-6, 2021

Where: Virtual / Indonesia

Program Director: Prof. Mohammad Ashkan Moslehi, Prof. Wahyuni Indawa

Program Type: Educaonal seminar (postgraduate may include physicians in pracce and trainees), Confer-

ence (didacc lectures)

Website: hps://iprm2021.id/

• SCOPE 2021: Breaking Barriers in Lung Cancer (Philippines/Virtual)

When: June 23-25, 2021

Where: Virtual / Philippines

Program Director: Ronald A. Fajardo, MD

Program Type: Educaonal seminar (postgraduate may include physicians in pracce and trainees), Hands-on

workshop, Conference (didacc lectures)

Website: hp://www.scope2021.net/

• Introducon to Bronchoscopy and Pulmonary Procedures Course (USA)

When: June 27 and 30, 2021

Where: Beth Israel Deaconess Medical Center, Boston, MA, USA

Program Director: Mihir Parikh, MD

Program Type: Educaonal seminar (for trainees only), Hands-on workshop, Conference (didacc lectures)

“When in Doubt-Cut it Out” May Not Be the Best Strategy Anymore

With the implementaon of lung cancer screening, albeit fragmented, the numbers of pulmonary nodules discovered have increased exponenally

in the United States and the rest of the world. However, our capability to predict malignant from benign nodules remains unreliable and limited.

Performing biopsies or surgically removing all “high-risk nodules” is neither feasible nor sciencally sound, as shown by numerous clinical trials

including, the Naonal Lung cancer Screening Trial (NLST). NLST showed that more than 95% of surgeries in “high-risk paents” revealed non-

malignant nodules. Even with ever-evolving technologies such as navigaon and roboc bronchoscopies, sampling of nodules remains parcularly

quesonable when it’s negave.

Genec classiers are being developed and implemented to enhance pre and post-test probability of malignancy in pulmonary nodules to help

navigate invasive workup, parcularly, surgical procedures.

A study (1) of a genomic classier (Percepta) based on the “eld of injury” assessed cancer-associated gene expression in cytologically normal-

appearing bronchial epithelial cells in the mainstem bronchus in paents undergoing bronchoscopies and is able to disnguish malignant pulmo-

nary nodules from benign lesions. The study looked at two dierent cohorts. Two independent prospecve cohorts revealed that the gene-

expression classier had high sensivity across dierent lesion sizes, locaons, stages, and cell types of lung cancer. The combinaon of the classi-

er plus bronchoscopy had a sensivity of 96% and 98% in the both (AEGIS-1 and AEGIS-2) validaon cohorts. Consequently, Percepta successfully

down-classied nodules with an intermediate pretest probability of malignancy (10%-60%) to a low-risk probability of malignancy (< 10%) with a

91% negave predicve value.

Another recent study published in CHEST 2021 (2) set out to evaluate the impact of Percepta on clinical decision-making in a “real-world” seng.

This study is a mulcenter paent registry to observe a physician management of paents with pulmonary nodules who have had a nondiagnosc

bronchoscopy. Within that registry, the authors studied physician behavior and outcomes of decisions in paents with Percepta results. This sub-

set, the “decision impact study,” included documented physician risk assessment and decision-making results (planned and actual), in concert with

Percepta results to evaluate the impact on decision making of the test result.

In paents who were slated for invasive procedures (biopsy/resecon), the Percepta genomic classier downgraded one-third of (approximately

34%) of paents to lower risk of malignancy, precluding invasive procedures in approximately 79% of these downgraded paents for up to one

year. This study also showed that performing a genec classier tests did not delay in diagnosis of lung cancer.

Given this rapidly evolving data and the breadth of evidence, showing gene-expression classier improved the diagnosc performance of bronchos-

copy to detect lung cancer. Notably, in intermediate-risk paents with a nondiagnosc bronchoscopic examinaon, a negave classier score sup-

ports for a more conservave diagnosc approach.

I hope that our ability to predict the malignant potenal of a nodule improves substanally. Ulmately, we want to minimize unnecessary proce-

dures/resecon for non-malignant lesions and capture malignant lesions in me. Hence, when in doubt, consider genec classiers might be a

beer approach than “cut it out.”

Ali I. Musani MD

Editor-in-Chief: Dr. Kazuhiro Yasufuku

Research

Primary Business Address:

Kazuhiro Yasufuku, Editor-in-Chief

WABIP Newsleer

c/o Judy McConnell

200 Elizabeth St, 9N-957

Toronto, ON M5G 2C4 Canada

E-mail: newsleer@wabip.com

P A G E 17

Associate editor:

Dr. Ali Musani

Associate editor:

Dr. Sepmiu Murgu

References:

1. Silvestri GA et al; AEGIS Study Team. N Engl J Med. 2015 Jul 16;373

(3):243-51. doi: 10.1056/NEJMoa1504601. Epub 2015 May 17.

2. Lee HJ et al. Chest. 2021 Jan;159(1): 401-12. doi: 10.1016/

j.chest.2020.07.067. Epub 2020 Aug 3.

P A G E

WABIP ACADEMY- WEBCASTS

The WABIP has started a new educaon project recently: THE WABIP ACADEMY. The WABIP Academy will pro-

vide free online webcasts with new and hot topics that will interest pulmonologists and intervenonalists.

Current webcast topic: Tissue acquision for biomarker directed therapy of NSCLC

You can reach these webcasts by using this link: hp://www.wabipacademy.com/webcast/

www.bronchology.com Home of the Journal of Bronchology

www.bronchoscopy.org Internaonal educaonal website for

bronchoscopy training with u-tube and

facebook interfaces, numerous teachiing

videos, and step by step tesng and assess

ment tools

www.aabronchology.org American Associaon for Bronchology and I

ntervenonal Pulmonology (AABIP)

www.eabip.org European Associaon for Bronchology and

Intervenonal Pulmonology

W A B I P N E W S L E T T E R

Links

www.chestnet.org Intervenonal Chest/Diagnosc Procedures (IC/DP)

NetWork

www.thoracic.org American Thoracic Society

www.ctsnet.org The leading online resource of educaonal and

scienc research informaon for cardiothoracic

surgeons.

www.jrs.or.jp The Japanese Respirology Society

sites.google.com/site/asendoscopiarespiratoria/

Asociación Sudamericana de Endoscopía Respiratoria

P A G E 18