Therapeutic bronchoscopy for central airway diseases

Mechanical debulking

Abnormal tissue of both malignant and benign origin can be removed directly with forceps or by pushing the distal bevelled edge of the rigid bronchoscope against the base of the lesion and coring it out under direct visualisation, often using a suction tube or grasping forceps. In order to avoid excessive bleeding following the coring out of the lesion, it is advisable to first coagulate/devascularise the lesion using thermal ablation techniques. After resection, the barrel of the rigid bronchoscope is advanced distally so that haemostasis is effectuated by the radial compression that is exerted on the airway wall by the rigid tube (figure 2). This technique is the quickest way to resect and remove tumours and to control bleeding coming from its base. Nevertheless, it can be difficult in long tumours because portions of resected tumour and blood get into the lumen and vision is blurred. At that point it is crucial not to lose the axis of the airway in which the resection is performed otherwise perforation can occur. In cases in which an attempt to resect has provoked massive bleeding and the procedure has been halted it is possible to reschedule the resection after embolisation [6]. A micro-debrider is an auxiliary instrument with a long disposable rotating blade coupled with suctioning. Debulking with this technique is quick, but control of bleeding may require adjunctive bronchoscopic thermal haemostatic/ablative modalities [7]. Whenever there is important bleeding after mechanical debulking which cannot be effectively controlled by standard measures (compression with the shaft or thermal coagulation), the insertion of a Fogarty balloon (4 or 6 Fr) may block the airway and preserve ventilation in the contralateral lung [7].

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FIGURE 2

Mechanical debulking with the tip of the rigid bronchoscope.

Thermal ablation

Laser stands for “light amplification of stimulated emission of radiation”. This light can be delivered through optical fibres suitable for bronchoscopic applications. Laser wavelength and power density (Watts·mm⁻²) are the main characteristics that define the suitability of each laser for endoscopic treatment. Depending on the laser wavelength, effects can penetrate up to 10 mm and have a bigger or smaller ratio of absorption and scattering in soft tissue (figure 3). The absorption and scattering of the laser beam also depends on tissue composition (e.g. water, blood, fat) and its colour. Dark tissues absorb nearly all the light, whereas clear colours let the light penetrate further. Lasers with high absorption and scattering coefficients, like the Nd:YAP (Nd-doped yttrium-aluminium-perovskite) with a 1340 nm wavelength, are potent coagulators but have poor cutting precision. However, CO₂ LASER with a 10 600 nm wavelength has a poor coagulation effect but far superior cutting precision. Power density mainly depends on the watts delivered and the distance between the tip of the laser fibre and the target. Distance is highly determining of power density; as distance increases, the power density diminishes as well as the effect on tissue. Laser can be used in noncontact mode within air-cooled catheters or in contact mode, with nude fibres. Noncontact mode allows the surgeon to work easily without the need for the constantly cleaning of the tip of debris and blood. Current laser equipment is smaller, more portable and more affordable than ever.

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FIGURE 3

Laser yttrium aluminium perovskite photocoagulation on a tracheal tumour.

The photocoagulation effect is easily seen as the tumour surface turns white, which is known as the blanching effect. This is achieved at low power settings and/or by placing the tip of the laser probe 1 cm away from the target. If the power density increases by raising the power and/or advancing the tip of the laser probe, the tissue is carbonised and vaporised, and the operator observes a blackening and charring of the tumour.

The laser fibre can also be used through the flexible bronchoscope while the flexible scope is passing through the rigid scope thus combining all available modalities [8–10]. Protective eyewear is mandatory when the laser beam is activated, though the risk of harm to medical personnel is minimal since observation is performed via video camera. Reducing inspiratory oxygen fraction <40% when activating LASER, electrocautery or APC (discussed below) is advised to prevent endobronchial fire. If jet ventilation is used, it is preferable to discontinue the jet while activating the thermal modality.

Electrocautery is a contact mode ablation technique based on electric current flow. Electrons generate heat for tissue coagulation due to the higher resistance of the target tissue. Different types of unipolar electrodes are available (including blunt probe, knife, forceps and wire snare loops) but achieving the essential contact of the probe with the mucosa (thus suctioning secretion, blood or debris) at the site of treatment is of utmost importance for this technique to be effective. Tissue effect depends on the wattage setting, the surface area of contact (a smaller probe will increase current density) and the time during which energy is applied [11–14]. A new catheter that allows for coagulation and cut modes with a depth of penetrations <2 mm and with an integrated suction function has also been introduced recently with promising results [15]. One of the limitations of monopolar electric current modalities is the interaction they might have with pacemakers, which have to be inactivated before the initiation of the procedure.

APC is a noncontact technique that utilises ionised argon gas (plasma) to conduct monopolar electrical current to the nearest tissue. Its depth of penetration is <3 mm, making APC very safe but useful mainly for coagulation/haemostasis or for treating superficial and flat lesions [16, 17]. APC is suitable for treating bronchial segments at an acute angle (i.e. apical and posterior segments of the upper lobes) because the argon gas flows around bends and corners. This approach offers an advantage over laser bundles, which always leave the probe in a straight path. Although argon is generally safe and is not combustible in itself, endoscopic fire can be ignited in its presence together with high oxygen concentrations. Gas embolisation is a rare, albeit the most severe (sometimes fatal) complication that may be encountered when using APC [12, 18].

Electrocautery/APC purchase and maintenance costs are low; applicators are re-usable and cheap and can be used through the flexible bronchoscope as well, while the technique is simple and easy. In comparison, LASERs come with a much higher cost of implementation and maintenance, have a steeper learning curve and are more dangerous. Although lasers may in general be more powerful and rapidly effective, when building a new interventional pulmonology unit, electrocautery/APC as far as the thermal ablation technique goes, offers more logistical advantages over laser [12, 13].

Photodynamic therapy is a unique biopharmaceutical modality where an injectable photosensitising drug delivered prior to the procedure is selectively retained in tumour cells and is subsequently activated by specific wavelength light. This creates reactive oxygen species resulting in local cytotoxicity and an enhanced anti-tumour response allowing for destruction of tumour sites. The tumour undergoes necrosis after exposure to light and debris accumulates at the site over the next 48 h. A second bronchoscopy is required 2–3 days after each light administration for the debridement and the re-establishment of airway patency. Photodynamic therapy is approved for use as a definitive treatment in early stage superficial lung cancer and palliation in advanced stages of the disease. However, due to its prolonged photosensitisation, it is not practical to use in regions with ample sunlight. Given its high cost and complicated logistics, as well as the delayed effect of its action, it does not present any special advantage over the other thermal techniques described above. Its use, however, is suggested as part of a multimodality approach scheme [19–21].

Cryotherapy

Freezing of the bronchoscopic cryoprobe is achieved with the Joules–Thomson effect: the expansion of a previously compressed gas generates an immediate drop in temperature. The most common gases for medical use are nitrous oxide or carbon dioxide, which are decompressed at the tip of the cryoprobe, generating a freezing effect of −70 to −90°C. The endoscopic application of extreme cold can be used for three purposes. 1) Cryo-recanalisation is a contact mode based on the adherence of the tumour to the end of the frozen cryoprobe and its immediate retraction along with large fragmented tissue. Large pieces of tumour can be removed instantly with this technique, though thermocoagulation may be required afterwards to control bleeding [22–24]. 2) Cryotherapy can also be applied as a delayed effect technique based on the cellular damage produced by repeated cycles of freezing and thawing. It produces delayed necrosis followed by sloughing, which may be expectorated or removed bronchoscopically. 3) Cryo-spray, a noncontact mode, has also been introduced recently. A specialised flexible catheter delivers liquid nitrogen uniformly. This noncontact mode technique achieves 5 mm depth of tissue destruction in <10 s. Despite these advantages and the relative simplicity of the procedure, there is also a risk of severe barotrauma if the gas is not vented. When liquid nitrogen is released into the warm airway, there occurs an almost instantaneous conversion to gas with a resulting volume expansion of the order of 1:645. The main risk is therefore barotrauma including pneumothorax, pneumomediastinum and nitrogen gas embolism, which, though rare, can prove fatal [25].

Balloon dilatation

High-pressure balloon dilatation is a useful and easy-to-perform technique for opening stenotic airways. Balloons are made of low-compliance inflatable polymers that allow for a uniform and reproducible expansion to a specified diameter on inflation. They are filled with saline and hydraulic pressure of the balloon is monitored manometrically, achieving an excellent correlation between diameter and pressure. Wire guidance with or without fluoroscopy support is used to pass through a high-grade stenosis or across an irregular stenosis when bronchoscopic guidance is not feasible.

It is important to select an appropriate size for the balloon, in terms of both length and final diameter, as too short a length will result in the slipping of the balloon, while excessive length could potentially result in distal airway trauma. Excessively small diameters will not obtain significant changes and too large diameters can easily provoke complications. Mucosal and transmural tearing, bleeding, pneumomediastinum and pneumothorax have been reported [26, 27]. Special caution is needed when the stenosis is not fully circumferential and the healthy posterior wall is exposed to high pressure. To prevent many complications, a step-by-step increment of pressure in 30 s to 1-min periods is recommended to achieve smooth dilatation.

The dilation effect of the balloon is usually temporary and complementary techniques are therefore usually required after dilatation, such as debulking, resection, ablation, stent placement and mitomycin C application [28–30].

Stents

Silicone or self-expandable metallic stents (SEMS), either fully or partially covered, may achieve sustained dilatation on the stenotic portion of the airway and assure ventilation. Silicone stents have thicker walls than metallic stents (1 mm versus 0.25 mm), are less adaptable to airway anatomy and always require a rigid bronchoscope to be implanted and removed (figure 4). However, they can remain in place for years and are much easier to remove.

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FIGURE 4

a) Silicon and b) metal stents.

SEMS have a better performance in malignant airway stenosis with a complex or conical anatomy including fistulas and can be implanted with a flexible or rigid bronchoscope. Nevertheless, rigid bronchoscopy always guarantees a better airway control.

Since 2005, following a US Food and Drug Administration (FDA) recommendation, metallic stents have not been used for benign airway strictures due to the high rate of complications and even deaths reported. Nevertheless, a new generation of SEMS has been commercialised since this warning. These fully covered SEMS have been tested in small retrospective studies. One study with 16 patients did not register deaths associated with the stents and their removal was feasible in all the cases reported [31]. In a more recent study with 30 patients there were no associated deaths and successful removal was achieved in 90% of cases [32]. These studies show the feasibility and safety of these new stents, though a comparative study with the silicone stent as the gold standard is needed to draw robust conclusions. Complications are frequent with both types of stents. In a retrospective cohort study with follow-up bronchoscopies in 94 patients bearing 100 stents of various types, complications were detected in 69%. They were mainly obstruction by secretions (37%), obstruction by tumour/granulation tissue growth (27%) and migration (20%). A univariate analysis comparing fully covered SEMS and straight silicone stents did not reach statistical significance (OR 0.17 (95% CI) 0.03–1.00) [33].

The introduction of self-expanding metallic tracheobronchial bifurcated “Y-shaped” stents has resolved some of the limitations of the silicone Y stents, including asymmetrical main bronchi diameters, pure extrinsic compression and wide main carinas. The procedure is usually performed under fluoroscopy, which provides full visual control. On some occasions, these stents have been implanted with flexible bronchoscopy [34]. Nevertheless, their removal is only possible under rigid bronchoscopy.

Customised silicone stents are set to play an essential role in the near future as complex anatomy indications are resolved and many complications, such as migration and granulation, are considerably diminished. The first published use of an airway customised three-dimensional (3D)-printed silicone stent took place in France in 2017. This stent was used successfully on a patient with stenosis and partial dehiscence of the bronchial anastomosis in his lung allograft [35]. More recently, US FDA clearance to implant a 3D-silicon stent that had been customised for compassionate use was obtained for the first time in the USA. Two patients with complicated airway disease due to granulomatosis with polyangiitis were successfully stented [36]. Nevertheless, there remain regulatory and technological difficulties to overcome before customised silicone stents can be made commercially available. Randomised comparative studies will be needed before the inclusion of new generation stents in the guidelines.