ARIF R HANAFI “Dharmais” Hospital National Cancer Center Indonesia

KONKER PDPI XVI Workshop Intervention Solo, 12 September 2019

Introduction

The late 18th century where rigid illuminating tubes were used to examine the tracheobronchial tree.

Fiberoptic bronchoscope by Ikeda et al., has revolutionized the practice of pulmonary medicine.

In cancer, advances in real-time imaging and catheter-based techniques,

Diagnosis and staging

Therapeutic intervention for airway restoration in central airway obstruction

Treatment of early detected central airway cancers.

Peripheral lung nodules that are beyond the visibility of the bronchoscope, (CT) guided, navigational methods, and endobronchial ultrasonography (EBUS) facilitate accurate targeting.

Chest Surg Clin N Am 1996;6:381–395. J Med 1968;17:1–16. Clin Chest Med 1999;20:1–17.

Schieppati

Schieppati E. La puncion mediastinal a traves del espolon traqueal. Rev As Med Argent 1949;63:497.

Things to Consider

Personel

Scope of practice

Equipment

Space/unit

Practice environment

Financial

Personel

A bronchoscopist alone is not enough

Nursing, ancillary help(minimal 2 nurses)

Anesthesiolog

Relationships with other services such as pathology & thoracic surgery

Requirements differ.

The type and the nature of lesion

The localisation of the lesion

The condition of distal airways

Available equipment must be preferred!

The experience of the physician

The cost of the technics

Which technical for which patient?

Flexible Bronchoscope Nomenclature

BF-Q180 BF-P180 BF-1T180 BF-3C 160

Insertion tube OD 5.1 mm 4.9 mm 6.0 mm 3.8 mm

Channel ID 2.0 mm 2.0 mm 3.0 mm 1.2 mm

Up/Down U:180

D:130

U:180

D:130

U:180

D:130

U:180

D:130

Working Length 600 mm 600 mm 600 mm 600 mm

Field of view 120 deg 120 deg 120 deg 120 deg

Forcep, needle, brush & electrocauter

Rigid bronchoscopy

Bronchoscopy space / unit

Diagnosis

Bronchial washing, brushing, and endobronchial and transbronchial biopsy have variable yields depending on tumor location and accessibility.

Endobronchial – forceps biopsy (74%) brushing (59%) washing (48%) combined (88%)

Peripheral – transbronchial brush + fluoroscopy (52%) biopsy (46%) washing (43%)

Bronchial washing, fluoroscopic-guided transbronchial biopsy, and brush are combined (69%)

C TBNA for endobronchial, submucosal, peripheral pulmonary lesion or peribronchial lymph node has been demonstrated to enhance diagnostic yield and is cost effective.

Chest 2003;123:115S–128S. Clin Chest Med 1999;20:39 –51. Am J Respir Crit Care Med 2000;161:601– 607.

Bronkoskopi

diagnostik

Bronkoskopi

Laringoskopi

ProofPunksi

PunksiPleura

WSDpigtail

Pleurodhesis

ReposisiWSD

TTNATTBCore

BiopsiFNAB

Jumlah 272 54 28 28 1013 492 249 518 83 83 61

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200

400

600

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1000

1200

Ju

mla

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Jenis Tindakan/tahun (2881)

Diagnostic Procedures in Dharmais NCCI 2016 - 2017

SMF Paru RS Kanker “Dharmais”, 2017

0

100

200

300

400

500

600

700

Bilasan Sikatan Biopsi TTNA TTB Corebiopsi

FNAB PunksiPleura

Positif 144 239 196 70 52 54 638

Negatif 128 33 76 13 31 7 375

[CELLREF]

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[CELLREF] [CELLREF] 89%

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Sensitivity Diagnostic Procedures in Dharmais NCCI 2016 - 2017

SMF Paru RS Kanker “Dharmais”, 2017

Guided Bronchoscopy in SPN

CT / flouroscopic guided Bronchoscopy (TBLB)

Ultrathin bronchoscopy

Peripheral radial EBUS / guide sheath

Electromagnetic Navigation Bronchoscopy (EMN)

super dimension, veran medical

Virtual brochoscopy navigation (VBN)

lung point, BF navigation

Bronchoscpy TransParenchymal Nodule Access (BTPNA)

Diagnosis

SPN is dependent on size, proximity to the bronchial tree, bronchus sign.

TBLB – > 2.5 cm is 62%, < 2.5 cm is 40%.

MDCT – 3D virtual bronchoscopy – precise biopsy using electromagnetic steering probe or ultrathin

ENB requires uploading chest CT data and selection of anatomic landmarks with virtual bronchoscopy before the procedure.

Patient is placed on an electromagnetic board and a sensor probe within a guide sheath (GS) inserted through the working channel of bronchoscope is used to align preselected reference points.

The probe is steered toward the target, and tissue sampling is performed with forceps, needle, or curette guided by sheath after withdrawal of the sensor probe.

Chest 2000;117:1049 –1054. Chest 2003;123:115–128. Eur Respir J 2004;23:776 –782. Chest 2006;130:559–566. Am J Respir Crit Care Med 2006;174:982–989.

ENB (Electomagnetic Navigation Bronchoscopy)

Not real time because the uploaded CT data

Diagnostic accuracy of 69 to 74%

Pneumothorax rate of 3%.

Median size of nodules biopsy is > 2 cm.

Localization of small nodules < 2 cm in the lower lobes and close to the pleura challenging.

The cost of ENB system is US $150,000 and another US $1000 for each disposable catheter.

Modification using the ultrathin bronchoscope.

EBUS radial probe is useful for sampling peripheral lesions.

Superiority of EBUS-guided TBLB (75%) over fluoroscopic-guided TBLB (31%) for SPN < 3 cm.

Eur Respir J 2007;29:1187–1192. Eur J Nucl Med Mol Imaging 2002;29:351–360. Chest 2004;126:959 –965.

Electromagnetic Navigation (EMN) inReach system (SuperDimension, Covidien)

EMN: Procedural steps

VBN (Virtual Bronchoscopy Navigation) Result (VBN+EBUS GS vs EBUS GS)

Nodules < 3 cm, Diagnostic yield 80.4% vs 67%, Shorter time in VBN group 24 min vs 26.2 min

Kurimoto et al. Diagnostic yield is higher when the radial probe is located within the lesion than when it is adjacent, efficacy of EBUS-GS method gives good yield.

SPN peripheral and close to the pleura – combined VBN and EBUS.

When the target was close, the sensor was removed and the EBUS probe was inserted.

Forceps biopsies were performed after EBUS confirmation that the catheter was close to the target

Combined VBN-EBUS (88%), VBN (59%) or EBUS (69%) alone, Iatrogenic pneumothorax was 6%,

VBN allows EBUS probe to the lesion, and real-time visualization and confirmation of target.

Asano et al,Thorax 2011; 66: 1072

Chest 2004;126:959 –965. Chest 2006;129:147–150.

Virtual Bronchoscopy Navigation (VBN) Procedural Steps

Technology Comparison EMN vs VBN

VBN: How Does it Work?

Planning Module:

Pre-procedure planning module/workstation used to download the CT, examine the lung in 3D, identify and select target locations, take airway measurements, then review virtual bronchoscopic pathway to target(s)

Procedure Module:

Intra-operative module/workstation used to synchronize images from the virtual bronch animation in the planning module, with the live video from the broncho scope during the procedure, providing real-time, directional path-overlay to targets

Bronchoscopic TransParenchymal Nodule Access : Archimides System

Staging with C TBNA

Under used - 12 % of pulmonologist routinely use TBNA in evaluation of malignant disease

Operator / assisant dependent - sensitivity ranges from 37 – 89 % - variable yield of 20 to 74%.

The puncture site for lymph nodes is first determined by flipping over CT images for better correlation with the endoscopic view.

Fear of puncture of vascular structures, damage to the bronchoscope, technical difficulties with needle, and inadequate specimen for diagnosis, TBNA is not routinely practiced.

Strategies to improve the yield of TBNA include minimum passes per lymph node station, ROSE, PET CT, EBUS guided and EMN / VBN.

Chest 1991;100:1668 Am Rev Respir Dis 1993;147:1251 Chest 1998;114:4

Eleven lymph node stations in Wang’s map: (A) endoscopic view, (B) correlated CT view and (C) relevant puncture site.

J Thorac Dis 2013;5(5):678-682. doi: 10.3978/j.issn.2072-1439.2013.09.11

www.radiologyassistant.nl

Sem Respir Crit Care Med 1997.p573

• Introduce needle into the scope channel with the scope tip straight and at midtrachea

• Advance and lock needle

• Retract catheter so that only tip of

the needle is visible

• Drive to puncture site and puncture bronchial wall perpendicullary

• Confirm penetration of entire length of needle

C TBNA RS Kanker Dharmais 2017

Tsuboi classification

Tsuboi classification of pulmonary nodule based on anatomical relationship with the adjacent bronchus

C-TBNA increases the diagnostic yield of flexible bronchoscopy while dealing with type III and IV lesions

J Thorac Dis 2015;7(S4):S256-S265

Staging with EBUS TBNA

Another major advance in mediastinal staging is the incorporation of curvilinear US to the tip of the bronchoscope that produces sectorial imaging of the lymph nodes.

Coupled with color flow Doppler, EBUS allows safe real-time aspiration of mediastinal lymph nodes by avoiding surrounding vascular structures, and accuracy between 89% and 97%.

EBUS coupled with US transesophageal sampling of enlarged lymph nodes in the mediastinum 94%.

Both techniques provide access to hilar, pulmonary ligament, para-esophageal, and adrenal lymph nodes that would otherwise be inaccessible with the mediastinoscope.

Am J Respir Crit Care Med 2005;171:1164 –1167. Thorax 2003;58:1083–1086. Eur Respir J 2005;25:416–421.

EBUS TBNA & radial GS

CENTRAL AIRWAY OBSTRUCTION DUE TO MALIGNANCY

Malignant central airway obstruction is a significant cause of morbidity and mortality.

30% of lung cancer will present with airway obstruction and 35% of this group will die of complications such as hemoptysis, post obstuctive pneumonia, and asphyxia.

Airway recanalization by bronchoscopic methods and stent placement provide rapid relief of symptoms and allow time for chemoradiotherapy for palliation, improved QoL, and survival.

Selection of a therapeutic strategy depends on

the type of lesion,

acuity of presentation,

the patient’s general health status, and

physician’s expertise.

J Thorac Oncol. 2010;5: 1290–1300

Intraluminal

Extrinsic

Mixed

CENTRAL AIRWAY OBSTRUCTION DUE TO MALIGNANCY

J Thorac Oncol. 2010;5: 1290–1300

Techniques for Immediate Airway Recannalization Laser Therapy

Neodymium-Yttrium-Aluminum- Garnet (Nd-YAG) wave length is poorly absorbed by quartz material & transmitted through a flexible fiber.

The flexibility of the fiber enables distal airway lesions to be treated with either the rigid or flexible bronchoscope & allows for coagulation at low power and vaporization at high power.

Can be used to restore airway patency emergently or electively, and effectively debulk tumors by a combination of coring out techniques, deep tissue coagulation, and vaporization.

Very effective not only for symptom palliation such as cough, dyspnea, and hemoptysis but also in achieving endoscopic, radiographic, spirometric, and QoL improvements.

Timely recognition and prompt intervention avoid mechanical ventilation Chest 1988;94:15–21.

Thorax 1985;40:341–345. Chest 1988;93:65– 69. Chest 1997;112:202–206.

Factors that Influence Outcome of Nd-YAG

Factors Favorable Unfavorable

Location Trachea main bronchi Lobar, segmental bronchi

Type of lession Endobronchial Extrinsic

Appearance Polypoid, exopitic, pedunculated Submucosal

Extent of involvement Localized (one wall) Extensive (1> wall)

Length of lession <4 cm > 4cm

Distal lumen visible Not vissible

Duration of collapse <4-6wk > 4-6 wk

Clinical status

Hemodynamics Stable Unstable

Oxygen requirement <40% FiO2 >40% FiO2

Coagulation profile Normal Abnormal

Pulmonary vascular Intact Compromised

J Thorac Oncol. 2010;5: 1290–1300

Techniques for Immediate Airway Recannalization Endobronchial Electrosurgery and Argon Plasma coagulation

EBES

As effective as the laser for ablation and control of hemoptysis, but cheaper and portable.

Can be performed through rigid or flexible bronchoscope

Contraindicated for patients with cardiac pacemaker.

Contact technique that is effective for tumor debulking

“Cut,” “coagulate,” or “blend” by varying the amperage and voltage

Not only suitable for incision but also effective hemostasis with minimal tissue injury.

APC

Electrosurgical allow electrical to be applied in a noncontact mode through ionized argon gas,

Homogenous conduction of electrons, and also around corners useful for hemorrhagic tumors,

Difficult to access upper lobe tumors and granulation around stents. Eur Respir J 2006;27:1258 –1271. Lung Cancer 2001;33:75– 80. Chest 2001;119:781–787. Respirology 2006;11:643– 647.

Techniques for Delayed Airway Recannalization Brachytherapy

Temporary placement of encapsulated radioactive sources near or within an endobronchial or parabronchial malignancy to deliver local irradiation. implanted directly into the tumor

Improvements in the after loading technique with iridium-192 enable bronchoscopic administration of high dose-rate brachytherapy on an outpatient basis with minimal hazard to healthcare personnel.

Advantage is it allows high-dose irradiation of the tumor with rapid fall-off outside area.

Curative for early central airway cancers, small endobronchial and peripherally located tumors

Contraindicated in tumors that invade major arteries or structures within the mediastinum, and complications include radiation bronchitis 10% and hemoptysis 7%.

Radiother Oncol 1995;35:193–197. Int J Radiat Oncol Biol Phys 1998;42:21–27. Chest 1997;112:946 –953.

Techniques for Delayed Airway Recannalization Cryotherapy Repetitive rapid cooling and slow thawing with a special probe that conducts liquid nitrogen N2O. Intracellular ice-crystal formation that causes cell death and tissue destruction.

Three cycles of freezing and thawing are performed and each freezing period lasts 20 seconds. Applied to treat malignant airway lesions and an ideal lesion for cryotherapy is a small, polypoidal

tumor that is accessible to the probe with distal visibility of bronchial segments

Performed with the rigid or flexible cryoprobe and the immunogenic effects of chemoradiation Delayed vascular thrombosis and necrosis, removed large endobronchial tumors obstructing

the central airways in which the cryoprobe tip is pushed into tumor, and freezing starts for 5 seconds.

Cryoprobe is abruptly removed together with tumor tissue frozen at the tip. Procedure is repeated until the tumor mass has been removed and the bronchus recannalized. Success in airway recanalization is more than 90% without complications. Tissue specimens obtained with the cryoprobe are larger and of superior compared with forceps.

Chest 1992;102:1436 –1440. J Thorac Cardiovasc Surg 2004;127:1427–1431. Respiration 2009;78:203–208.

Techniques for Delayed Airway Recannalization Photodynamic Therapy

Causes tissue necrosis through toxic oxygen radicals produced by the combined effect of a tumor-localizing photosensitizer dihematoporphyrin ether/ester

Photofrin is administered iv at 2 mg/kg and is retained preferentially by tumor,

Exposed to laser light 40 to 50 hours later, which initiates cell death by superoxide and hydroxyl radicals, and tissue necrosis by vascular thrombosis from thromboxane A2 release.

Indicated for non emergent palliation of obstructing tumors, treatment of early lung cancers.

Moghissi et al. showed that when treat 100 patients with airway obstruction, airway patency improved by 68% with corresponding increases in FVC and FEV1.

Complications are few such as dyspnea from airway obstruction because of tissue swelling, photosensitivity, and hemoptysis

Need for regular clean up bronchoscopy, avoidance of sunlight for 2 to 6 weeks depending on the photosensitizer and the relatively high cost make PDT less attractive.

J Thorac Cardiovasc Surg 1997;114:940 –

946. J Thorac Oncol 2006;1:489–493. Eur J Cardiothorac Surg 1999;15:1– 6.

The Joule – Thomson principle

The decrease in temperature that is observed during the expansion of gas from a highpressure to a low-pressure environment.

Nitrous oxide (N2O), which is stored at room temperature under high pressure,

N2O is released at the tip of the cryoprobe, the temperature falls to –890C within several seconds.

Maiwand MO, Homasson JP. Cryotherapy for tracheobronchial disorders. Clin Chest Med 1995;16:427–443.

CRYOSURGERY IN CENTRAL AIRWAY OBSTRUCTION (CAO)

Brachitherapy

Brachitherapy

EXTRINSIC AIRWAY COMPRESSION

Stents

Airway stent insertion is effective in maintaining airway patency from extrinsic compression

Available types include silicone tube, covered / uncovered metallic, and hybrid stents.

Silicone Tube Stents

These stents are advantageous because they can be customized to conform to the airways.

The silicone Y stent can be used if the distal trachea, bifurcation, and proximal bronchi are compressed or infiltrated by tumor.

Silicone stents can be easily repositioned and removed, and is less expensive.

Associated with a higher migration rate and require the rigid bronchoscope for insertion.

Chest 1990;97:328 –332. Chest 1993;104:1653–1659.

EXTRINSIC AIRWAY COMPRESSION Metallic Stents

Stents can be placed with the flexible bronchoscope

Greater airway cross-sectional diameters, conform better to tortuous airways allow for mucociliary clearance and ventilation across a lobar bronchial orifice

Disadvantages include obstructing granuloma, cracks from metal fatigue, and difficulty in removal or repositioning after epithelialization

Tumors can grow through the gaps of uncovered metallic stents, covered ones with silicone membrane of appropriate size and length should be used.

If the airway becomes occluded by tumor ingrowth or granulation tissue, laser should be avoided, because covered metallic stents are flammable, cryotherapy or APC used in conjunction with brachytherapy are safe and effective alternatives.

A new self-expanding nitinol Y stent has been described for treatment of central tumors affecting the distal trachea, bifurcation, and proximal main bronchi. Chest 2003;124:1993–1999.

Chest 2005;127:2106 –2112.

Indication for Stent Placement

Airway obstruction from extrinsic bronchial compression or submucosal disease

Obstruction endobronchial tumor when patency is <50% after bronchoscopic laser therapy

Aggressive endobronchial tumor growth and recurrence despite repetitive laser treatments

Loss of cartilaginous support from tumor destruction

Sequential insertion of airway and esophageal stens for tracheesophageal fistulas

J Thorac Oncol. 2010;5: 1290–1300

Comparison of the Dumon stent and the Covered Ultraflex Stent Characteristics Dumon Stent Covered Ultraflex Stent

Mechanical considerations

High interneal to external diameter ratio - +++

Resistant to compression when deployed + ++

Radial force exerted uniformly across stent + ++

Absence of migration - ++

Flexible for use in tortuous airways - +++

Removable +++ -

Dynamic expansion - ++

Can be customized +++ -

Tissue stent interaction

Biologically inert ++ ++

Devoid of granulation tissue + -

Tumor ingrowth ++ +

Ease of use

Can be deployed with FB - +++

Deployed under local anesthesia with conscious sedation - ++

Radiopaque for position evaluation - +++

Can be easily repositioned ++ -

Cost inexpensive + - J Thorac Oncol. 2010;5: 1290–1300

J Thorac Oncol. 2010;5: 1290–1300

EARLY LUNG CANCER DETECTION AND INTERVENTION Autofluorescence Bronchoscopy

Bronchial surface is illuminated by light (absorbed, reflected, back scattered, induce fluorescence).

Reflectance imaging defines structural features of bronchial epithelium to discriminate normal from abnormal, whereas AF bronchoscopy depends on the concentration of fluorophores

The spectral differences between 500 and 700 nm for normal, preneoplastic, and neoplastic tissues serve as basis for the development of AF-reflectance imaging devices (D-light, SAFE 3000, AFI).

Superiority of AF white-light bronchoscopy for the detection of preinvasive & early lung cancer.

AF has a high false-positive rate when bronchitis or airway inflammation is encountered.

Thorax 2005;60:496 –503. J Natl Cancer Inst 2001;93:1385–1391. Lung Cancer 2006;52:21–27. Chest 1998;113:696 –702.

EARLY LUNG CANCER DETECTION AND INTERVENTION

Real-time AF-imaging using SAFE 3000 - sensitivity (0.85) for the detection of preinvasive lesions with specificity (0.94) for targeted biopsy.

Calculating the red to green ratio of the abnormal airway site, color fluorescence ratio of > 0.54 correlated with moderate to high grade dysplasia and could serve as an objective guide to biopsy.

Narrow band imaging (NBI) technology, blue light (390–440 nm) - superficial capillaries and green light (530–550 nm) - blood vessels beneath the mucosa

Correlation between bronchial vascular pattern and angiogenic squamous dysplasia recognized as early cancer and bronchoscopic imaging tool for the detection of preneoplasia. - Herth et al.,

NBI was found to be more specific than AF without compromising sensitivity in the detection of airway preneoplastic lesions. Lung Cancer 2007;58:44–49.

Clin Cancer Res 2009;15:4700–4705. Thorax 2003;58:989 –995. Chest 2007;131:1794 –1799.

RFA & BTVA

Use RFA transthoracally or bronchoscopically to ablate tumor core

Use BTVA vapor to take a margin

RFA & BTVA Vapor ablation of tumors followed by resection

Bronchoscopic segmentectomy

Posisible to target tumor with VBN

8 sec ablation – 10 min procedure

Uniform field of necrosis (margin) around tumor

A – 5 mm B – 5,7 mm C – 6,4 mm

Good ratio

Good ratio for an effective airway secretions removal

Lindholm C et al. Chest 1978, 74: 362-367

Φ5.9 Φ4.9 Φ4.0 Φ2.8

Airway resistance (Raw) during FOB

Difficult intubation in malignancy

CONCLUSION

These are indeed exciting times for pulmonologist interested in lung malignancy therapy.

Novel imaging tools, and techniques improve cancer detection at the early stages and when combined with precise staging allow institution of lung preservation strategies.

Although randomized clinical trials in diagnostic and therapeutic bronchoscopy are few, use of appropriate technologies depends on the skill of the bronchoscopists and availability of equipment.

In patients with advanced cancer for whom palliation is required, opportune use of interventional bronchoscopic techniques provide symptom relief, longer survival, and improved quality of life.

Thank you