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Innovations in Interventional Pulmonology

By Venk Lakshminarayanan, MD, Ph.D.

Traditional bronchoscopy is a procedure allowing direct visualization of the tracheobronchial trees of the airway. Historically, the main types of bronchoscopy are rigid and flexible. Flexible bronchoscopy allows for visualization of the lumen, mucosa of the trachea, proximal airways and segmental airways to the third generation of segmental bronchi.

This device allowed for focused obtainment of specimens as part of the evaluation for infectious, malignant or alternative etiologies. Additionally, it is used to diagnose or treat abnormalities within or adjacent to these airways.

Extrinsic compression of the airway from a mass can be assessed as well as direct sampling of peribronchial masses with transbronchial needle aspiration (TBNA). With the advent and initiation of fluoroscopic guidance, there was increased sensitivity in the ability to biopsy peripheral lung lesions which were not directly visualized in an airway.

Bronchoscopy has evolved greatly over the past decade with advances in endoscopic and pathological technologies. Traditional use of fiberoptic bronchoscopy limited tissue sampling to larger (> 2 cm) and more central lesions. With the development of electromagnetic navigation bronchoscopy (ENB) and radial probe ultrasound guidance, we can now access and obtain diagnostic tissue from the peripheral lung nodules with greater sensitivity and at smaller sizes.

Figure 1 - Interventional Pulmonology

Figure 1: Right lower paratracheal lymph node 4R in a patient with a right upper lobe lung mass right mediastinal lymph adenopathy. The white arrow indicates the lymph node. The blue arrow notes the lower border of the azygous vein. Samples taken by L-EBUS were consistent with non-small cell lung cancer. This was consistent with the previously biopsied right upper lobe mass.

These procedures enable the experienced interventionalist to access most mediastinal lymph nodes to provide a complete staging procedure. ENB, which combines bronchoscopy with electromagnetic navigation, allows the interventional bronchoscopist to sample significantly smaller and more peripheral lesions. The use of a linear probe EBUS (L-EBUS) allows for sampling of enlarged mediastinal, hilar lymph nodes or masses, potentially eliminating the need for mediastinoscopy. Endobronchial ultrasound-guided TBNA is a less-invasive alternative in staging of lung cancer in addition to diagnosis.

The presence of lymph node metastasis remains one of the most adverse factors for prognosis in non-small cell lung cancer (NSCLC). The presence of mediastinal lymph node involvement may indicate the presence of stage IIIA or IIIB, thereby suggesting either inoperability or the need for adjuvant chemotherapy and/or radiotherapy.1

Sampling Lymph Nodes and Peripheral Modules

There are three techniques involved in interventional pulmonology in the diagnosis, staging and treatment of potential lung cancers: endobronchial ultrasound (EBUS), electromagnetic navigational bronchoscopy (EMB) and photodynamic therapy (PDT).

Endobronchial ultrasound (EBUS) is a bronchoscopic technique that uses ultrasound to visualize structures adjacent to the wall of the bronchus. It allows for rapid pathologic staging of mediastinal and hilar lymph nodes,1 as well as for pathologic evaluation of nodal disease, which may be seen during radiographic staging.

EBUS is different than endoscopic ultrasound (EUS). While both visualize and guide sampling of lymph nodes, EBUS is performed during bronchoscopy for mediastinal lymphadenopathy. There are two types of EBUS: radial probe EBUS (RP-EBUS) and linear probe EBUS (L-EBUS). The RP-EBUS provides 360-degree circumferential images of the airway wall and surrounding structures.

Figure 2

Figure 2: Electromagnetic Navigational Bronchoscopy (ENB). Image 2A demonstrates the 3-D reconstructing virtual image of the mass following CT scan. Images 2B, 2C and 2D demonstrate the left lower lobe mass by CT imaging. Figure 2E demonstrates the ENB-generated directed pathway to the nodule.

A major advantage of RP-EBUS is its ability to visualize the layers of the airway wall in detail. In contrast, the L-EBUS provides a view that is parallel to the shaft of the bronchoscope with view 30 degrees forward of oblique. Color flow and Doppler features permit identification of vascular, ductal, and cystic structures. The major advantage of L-EBUS is its ability to guide real-time sampling. Coupled with rapid onsite evaluation (ROSE) by a cytopathologist allows for expedited pathologic staging of lymph node. Figure 1 demonstrates a right lower paratracheal lymph node (4R station) seen with an L-EBUS probe, in a patient with a peripheral lung mass with associated adenopathy.

Another area of interventional pulmonology that has rapidly developed recently is electromagnetic navigation bronchoscopy (ENB). ENB allows for more accurate targeting of peripheral lung lesions for biopsy over traditional bronchoscopy with fluoroscopy.The combined modalities of ENB and RP-EBUS can increase the sensitivity of diagnostic yields, especially with peripheral lung nodules, which is of great advantage for nodules as small as 10 mm.

Figure 2 demonstrates a left lower lobe lung nodule biopsied under ENB. Coupled with L-EBUS, this two-staged procedure allowed for diagnostic sampling of the peripheral lung mass and mediastinal lymph nodes. This allowed pathologic staging of this lung mass, and the mediastinal adenopathy results in an expedited diagnostic pathway with increased sensitivity in lung cancer staging. The goal of these combined modalities is to provide a greater patient experience and reduce time to initiate treatment.

Figure 3

Figure 3A: the initial obstructing right main-stem mass consistent with known metastatic adenocarcinoma.

Surgical resection of some early-stage tumors may be contraindicated because of concerns regarding reduced postoperative pulmonary function, ventilation or poor preoperative functional status. Up to 10 percent of patients successfully resected with lung cancer subsequently develop a second primary lung neoplasm.2

Using varying doses of low-intensity laser irradiation, cell growth functions can be stimulated or inhibited.4 One such treatment strategy used on cancer cells PDT, in which cancer cells are treated with a photosensitizer (PS) in combination with laser irradiation. Individually, they are non-toxic. However, with light-activation, reactive oxygen species are generated inducing cancer cell death.4 Cell-specific photosensitizers are in development for future cancer treatment.

Figure 4

Figure 3B: the mass following Photfrin© and first laser light treatment. The mass appears mucoid and less vascular.

After a photosensitizer is administered and the tumor is visualized, the light fiber is introduced through the working channel of the bronchoscope, and the rigid cylindrical tip of the light fiber is embedded into the lesion. This not only protects healthy mucosa from light exposure, but also delivers more energy to the tumor itself.

When the laser light is applied to the target area at the appropriate wavelength, the photosensitizer is activated, causing ROS generation that results in cancer cell death.5 A repeat bronchoscopy is planned 48 hours after the laser light exposure, when the inflammatory response is decreasing and tumor necrosis is achieved. At that time, all debris should be removed bronchoscopically.6

Figure 5

Figure 3C: the mass following the second light exposure and completion of debridement. Note that the right mainstem is patent and there is minimal scarring noted in the airway.

If a second operation may not be feasible for a patient, PDT can provide a therapeutic alternative that spares functional lung tissue required in lung cancer patients.3 Indications for PDT include treatment of micro-invasive endobronchial NSCLC in patients for whom surgery and radiotherapy are not indicated.3 Additionally, PDT can also be used to palliate symptoms in patients with completely or partially obstructing endobronchial masses due to non-small cell lung cancers.3

Figures 3A, 3B and 3C demonstrate a patient with a large right main-stem lesion recurrent NSCLC. In Figure 3A, the obstructing mass is noted in the right main-stem bronchus. Following the initial laser light therapy, the obstructing tumor was noted to have a more mucoid appearance allowing for initiating of debridement (Figure 3B). Serial light exposure and mechanical debridement allowed for local debridement of the complete obstructing mass (Figure 3C).

Interventional pulmonology is a rapidly burgeoning field providing novel and innovating, less-invasive ways of diagnosing and treating a variety of lung diseases. These are just a few of the novel diagnostic and therapeutic procedures available within the field of interventional pulmonology.


References

1. Spira A, Ettinger DS. Multidisciplinary management of lung cancer. N Engl J Med 2004; 350: 379–392

2. Chiaki E, Akira M, Akira S., et al. Results of Long-term Follow-up of Photodynamic Therapy for Roentgenographically Occult Bronchogenic Squamous Cell Carcinoma. Chest 2009; 136(2):369–375)

3. Moghissi K and K Dixon. Update on the current indications, practice and results of photodynamic therapy (PDT) in early central lung cancer (ECLC). Photodiagnosis Photodyn Ther. 2008 Mar;5(1):10-8

4. Crous, A., and H. Abrahamse: Lung cancer stem cells and low-intensity laser irradiation: a potential future therapy? Stem Cell Res Ther. 2013; 4(5):129.

5. El-Hussein A, Harith H, Abrahamse H. Assessment of DNA damage after photodynamic therapy using a metallophthalocyanine photosensitizer. International Journal of Photoenergy. 2012; 2012:1–10).

6. Edell ES, Cortese DA: Photodynamic therapy. Its use in the management of bronchogenic carcinoma. Clin Chest Med. 1995; 16(3):455).

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