67: Ablative Endoscopic Therapy for Endobronchial Lesions

Endobronchial lesions are caused by a variety of benign and malignant disease processes. When such lesions obstruct the central airways, trachea, or mainstem bronchi, they quickly turn life threatening. The incidence of central airway obstruction (CAO) has increased largely because of the prevalence of lung cancer. It causes significant morbidity and, without treatment, may lead to suffocation and death. This chapter reviews the gamut of available endobronchial techniques for managing acute CAO, including endobronchial resection with electrocautery, argon plasma coagulation, laser therapy, photodynamic therapy, cryotherapy, external beam radiation and brachytherapy, and airway stents. The most comprehensive use of these techniques should be offered at centers experienced in the management of complex airway disorders with the full array of endoscopic and surgical options at their disposal.

CAO causes significant morbidity and mortality in patients with malignancies that affect the upper airways. Although the precise incidence and prevalence of CAO are unknown, current lung cancer rates suggest that an increasing number of patients experience complications of proximal endobronchial disease.¹ It has been estimated that approximately 20% to 30% of patients with lung cancer develop complications associated with airway obstruction (i.e., atelectasis, pneumonia, or dyspnea)² and that up to 40% of lung cancer deaths are caused by locoregional disease.³ With increased use of temporary artificial airways, such as endotracheal intubation, in a growing elderly population, the incidence of CAO from malignant, nonmalignant, or iatrogenic complications is also predicted to rise.

The most frequent cause of malignant CAO is by direct invasion of an adjacent tumor, chiefly bronchogenic carcinoma, secondarily esophageal and thyroid carcinoma. Primary tumors of the central airway are relatively uncommon. Most primary tracheal tumors are squamous cell carcinoma or adenoid cystic carcinoma. Distal to the carina, the carcinoid tumors account for the majority of primary airway tumors.⁴ Distant tumors, such as renal cell, breast, and thyroid, also may metastasize to the airway. Although the epidemiologic data are limited, the most commonly encountered nonmalignant causes of CAO are stenosis from the proliferation of granulation tissue resulting from prior endotracheal or tracheostomy tubes, airway foreign bodies, and tracheo- or bronchomalacia.⁵

The clinical presentation of patients with CAO secondary to endobronchial lesions depends not only on the underlying disease but also on the location and rate of progression of the airway obstruction, the patient's underlying health status, and other associated symptoms, such as postobstructive sequelae. Mild airway obstructions may have only slight effect on airflow; hence, the patient may be asymptomatic. However, the inflammation associated with even mild respiratory tract infections can cause mucosal swelling and mucous production, which may further occlude the lumen. For this reason, patients sometimes are misdiagnosed with exacerbations of chronic obstructive pulmonary disease or asthma, especially when symptoms such as wheezing and dyspnea improve with therapy aimed at treating the superimposed infection.

Typically, the trachea must be significantly narrowed (<8 mm) before exertional dyspnea is noted. The lumen diameter must be less than 5 mm before symptoms occur at rest.⁶ As a consequence of the dramatic loss of lumen diameter necessary for the development of symptoms, there is no forewarning, and up to 54% of patients with tracheal stenosis present in respiratory distress.

When evaluating patients with suspected CAO, in addition to spirometric tests including forced expiratory volume in 1 second (FEV₁), functional vital capacity (FVC), and FEV₁/FVC ratio, it is crucial to examine the shape of the flow-volume loop. The characteristic blunting of the flow-volume loop that signals the presence of a CAO typically is seen before spirometry yields abnormal results but may not be recognized until the airway is already narrowed to approximately 8 to 10 mm.⁷

Although often obtained as the initial radiologic test, conventional chest radiographs are rarely diagnostic. Recent advances in airway imaging with CT scanning now permit multiplanar and three-dimensional reconstruction with internal (virtual bronchoscopy) and external rendering.^8,9 Excellent image quality can be achieved with low-dose techniques.¹⁰ These new imaging protocols are better able to characterize whether the lesion is intraluminal, extrinsic to the airway, or has features of both. Moreover, with the newer techniques, one can detect whether the airway distal to the obstruction is patent. Measurements of length, diameter, and relationship to other structures such as blood vessels are also more accurate.

Bronchoscopy (either rigid or flexible; see Chapter 54) is a necessary component of the preinterventional workup. Bronchoscopy provides the means for obtaining a tissue diagnosis, and nothing replaces direct visualization to assess the nature and extent of the obstruction. Other information useful for treatment planning, such as the relative amount of intraluminal and extraluminal diseases, is also obtained. Endobronchial ultrasound can be useful for the diagnostic workup of tracheal invasion and can aid in planning therapeutic interventions.¹¹

When the obstruction is severe, bronchoscopy may be difficult and potentially dangerous to perform because the instrument further diminishes the diameter of the remaining lumen and does not accommodate ventilatory support. In addition, conscious sedation may depress ventilation and relax the respiratory muscles, causing a relatively stable airway to become unstable. Access to a team skilled in advanced airway management is essential when undertaking flexible bronchoscopy.

Many of the ablative endoscopic techniques presented below are used together clinically. An algorithm is provided for endoscopic management and decision making in CAO (Fig. 67-1).

Bronchoplasty—Dilation of the Airways

In urgent cases, the airways may be dilated using the barrel of the rigid bronchoscope. In more controlled situations, sequential dilation with balloons is preferred. Sequential balloon dilation produces less mucosal trauma and limits the subsequent formation of granulation tissue. The technique has been used successfully for patients with airway stenosis after lung transplantation and surgical resection of the airway, patients with postintubation tracheal stenosis, and patients with malignant airway obstruction. It also has been shown to be safe, effective, and well tolerated in awake patients undergoing flexible bronchoscopy with conscious sedation.

Balloon bronchoplasty is particularly effective in preparing stenotic airways for stent placement, for expanding stents after insertion, and for placement of brachytherapy catheters that otherwise would be impeded by high-grade stenoses. Dilation alone is immediately effective for intrinsic and extrinsic compression, but the results are not sustained. The mucosal trauma itself may lead to granulation and, in fact, accelerate restenosis. For this reason, dilation is commonly followed by laser or stenting procedures.

The microdebrider, a tool borrowed from otorhinolaryngology, can be used to perform mechanical tumor excision in the trachea and mainstem bronchi. The microdebrider has a spinning blade that is contained in a rigid suction catheter and provides the ability to cut with suction to remove blood and tumor or granulation tissue.¹²

Electrocautery

The “active ingredient” of electrocautery is heat, which is generated by passing current from the probe to the tissue. The electric current leaves the body through a grounding plate. The amount and type of current, the characteristics of the tissue, and the contact area between the probe and the tissue all determine the amount of heat generated. The clinical result can vary from simple desiccation to tissue vaporization.

Since most commercially available bronchoscopes are not electrically grounded, the bronchoscopist may “become” the grounding electrode if the unipolar probe tip touches the scope while the current is on.¹³ Newer bipolar probes have been developed to eliminate this risk as the current completes the arc through the probe.

Electrocautery with a snare device is well suited for removing pedunculated lesions. By cauterizing the stalk of the lesion, most of the tissue can be removed without destruction and therefore is available for pathologic review. This method has been used with curative intent for patients with early-stage and intraluminal squamous cell lung cancer, as well as in advanced malignancies, combined with other modalities.¹⁴ The side effects of electrocautery include bleeding, airway perforation, endobronchial fire, and damage to the bronchoscope.

Argon Plasma Coagulation

Argon plasma coagulation is a form of noncontact electrocoagulation that can be used as an alternative to contact electrocautery and noncontact laser therapy. The plasma is formed when a 5000- to 6000-V spark created at the tip of the probe by a tungsten electrode ionizes argon gas released at the probe tip. The plasma seeks the nearest grounded tissue, producing coagulative necrosis. Argon plasma coagulation can be used to treat lesions lateral to the probe or to reach around corners to access pathology that otherwise would be inaccessible by laser therapy. Used endoscopically, a coagulation depth of 2 to 3 mm can be achieved.¹⁵ The technique produces excellent hemostasis and is associated with minimal risk of airway perforation. As the tissue coagulates and becomes desiccated, the resistance increases, suppressing further current conduction and limiting penetration.¹⁶ Argon plasma coagulation is not as useful on large, bulky tumors because, unlike laser therapy, tumor vaporization does not occur, and other modalities typically are required to achieve satisfactory tumor debulking.

Laser Therapy

Light amplification by stimulated emission of radiation (laser) technology was first described in the 1960s. With introduction of the neodymium:yttrium-aluminum-garnet (Nd:YAG) laser in 1975, laser tumor debulking became a mainstay of clinical practice. Before that time, CO₂ and argon lasers were the only available options, and for technical reasons, neither could be adapted for use with the bronchoscope. The Nd:YAG laser has a wavelength of 1064 nm and produces an invisible beam that lies in the infrared region and can be used with the flexible bronchoscope.¹⁷ Since there is less absorption by hemoglobin with the Nd:YAG laser, tissue penetration up to 10 mm can be achieved. Less precise than a CO₂ laser, the Nd:YAG laser treats a greater volume of tissue. The laser typically is used at a power of approximately 20 to 40 W. Pulse duration is 0.1 to 1.2 seconds. The laser is always aimed tangentially to the airway. A conservative approach is advised because the depth of penetration is not immediately apparent to the endoscopist, and frequent reanalysis of the lesion and reapplication of the laser are recommended.

The types of lesions most suitable for treatment with laser therapy are central, intrinsic, and short (<4 cm) lesions with a visible distal endobronchial lumen. Lesions that meet these criteria can be obliterated successfully, reestablishing patency of the bronchial lumen in more than 90% of cases.¹⁸

In experienced hands, the safety record of laser therapy is excellent. Significant complications develop in fewer than 5% of patients. A summary of nearly 7000 laser treatments revealed an overall complication rate of 0.99%.¹⁸ After laser therapy, however, additional treatment with radiation therapy, photodynamic therapy, or stenting is required to prevent local disease recurrence and renewed CAO.

Photodynamic Therapy

Photodynamic therapy is the process of activating a drug with nonthermal laser light to cause a phototoxic reaction that leads to cell death. Porfimer sodium (Photofrin) is the commonly used drug, and it is injected intravenously at a dose of 2 mg/kg. Although the drug is cleared from most organs within 72 hours, it has a preference for malignant cells, as well as the skin, liver, and spleen.¹⁸ The tumor-to-normal-tissue ratio is maximal at 24 to 48 hours. After approximately 48 hours, the application of light will preferentially treat malignant cells and thus limit toxicity to normal tissues. However, the compound is retained in the skin for up to 6 weeks, and patients are required to minimize light exposure to avoid burn injury to exposed areas of skin. Using a wavelength of 630 nm, a penetration depth of 5 to 10 mm can be achieved. The most common light source is the potassium-titanyl-phosphate pump dye laser, which can be carried via a quartz fiber and used with a flexible bronchoscope. The light is applied through a cylindrical diffuser that emits light laterally in all directions (360 degrees) or using a microlens that emits the light in a straight line. The probe tips are available in several lengths and can be inserted directly into the tumor or placed adjacent to the tumor.

The amount of energy delivered is proportional to the duration of light treatment. Approximately 200 J/cm² treated (400 mW/cm of length of diffuser for 500 seconds) is a common dose for the initial treatment session. The treatment takes approximately 8 minutes and therefore can be accomplished easily with outpatient flexible bronchoscopy under conscious sedation and local anesthesia. Cell death is achieved via a type II photooxidation reaction. Since the cytotoxic effect is delayed, follow-up bronchoscopies are necessary to remove secretions and cellular debris from the airways.

Photodynamic therapy is an attractive option for treating patients with lung cancer who are unfit for surgery. It can be curative for early-stage lung cancer of the airways, and if used for carcinoma in situ, the complete remission rate may be as high as 83%.¹⁹

The use of endobronchial ultrasound to help determine the extent of disease before injecting the patient with the photosensitizer also may be beneficial for a more precise delivery of laser light. The major downside to this technique, aside from inducing prolonged photosensitivity in patients with limited life expectancy, is the very high cost of the procedure, the need for multiple endoscopies in a palliative setting, and its ineffectiveness for nonmalignant applications.

Cryotherapy

Cryotherapy or cryosurgery effect tissue or tumor destruction through repeated exposure of the target tissue to freeze-thaw cycles using extremely cold temperature (below -40°C) delivered via nitrous oxide (N₂O) gas. The efficacy of this method depends on the rapidity of the freeze cycle, the lowest temperature attained, the number of freeze-thaw cycles, and the water content of the tissue. Maximal cellular damage is achieved with rapid cooling and slow thawing.

N₂O is stored at room temperature under high pressure. When N₂O is released at the tip of the cryoprobe, the temperature falls to -89°C within several seconds. Although liquid nitrogen also has been used, it peaks early, with maximal negative temperatures reached after 1 to 2 minutes, limiting the cellular injury as compared with N₂O.²⁰

Cryotherapy also can be used to remove blood clots and foreign objects with high water content such as grapes. Freezing the object to the probe tip permits the foreign body to be removed along with the cryoprobe and bronchoscope unit from the airways. Cryotherapy is a relatively safe technique. Since freezing and recrystallization depend on cellular water content, and cartilage and fibrous tissue are relatively cryoresistant, the incidence of airway perforation is markedly reduced. Bleeding also tends to be less common because of the hemostatic effects of cryotherapy. In addition, cryotherapy is not associated with the risk of airway fires, electrical accidents, or radiation exposure. The major disadvantage of cryotherapy is that its maximal effects are delayed, and it therefore should not be used to treat patients with acute, severe airway obstruction.

Cryotherapy can be delivered using both the rigid and flexible bronchoscopes. Rigid, semirigid, and flexible probes are available commercially. The size of the probe tip is proportional to the tissue injury. When using the flexible bronchoscope, it is crucial to have the probe protrude several millimeters from the distal tip of the scope so as not to freeze the video chip. Approximately three 60-second freeze-thaw cycles are performed in each area. Generally, however, cryotherapy is considerably less effective than other methods of tissue destruction and therefore is losing importance.

External Beam Radiation and Brachytherapy

External beam radiation to the chest is an established therapy for lung cancer and cancer-related complications. It is minimally effective, however, for cancer-induced airway obstruction. As many as 50% of patients receiving external radiation for local control will develop disease progression within the radiated field.²¹ The factor limiting most external beam radiation treatments in the chest is the unwanted exposure of normal tissue (i.e., normal lung parenchyma, heart, spine, and esophagus). Brachytherapy allows radiation to be delivered endobronchially, thus limiting exposure to normal tissues. The term brachytherapy, meaning “short,” signifies both the distance of the radiation source from the tissue being treated and the duration of therapy. Brachytherapy typically is performed with the radiation source remaining within the airway. The most commonly used source of radiation is iridium-192 (¹⁹²Ir), which is delivered via a catheter.

Most endoscopists recommend the afterloading technique. A blind-tipped catheter is placed at the desired position, and thereafter, the radiation source is loaded. A major advantage to this method is the ability to use higher-intensity isotopes without exposing the staff to radiation.

There is no consensus regarding dose rate and cumulative dose in distinguishing low-dose radiation, intermediate-dose radiation, and high-dose radiation brachytherapy. Low-dose radiation therapy has been arbitrarily defined as 75 to 200 cGy/h. The radiation source is placed adjacent to the lesion for 20 to 60 hours. A cumulative dose of 3000 cGy at a radius of 10 mm in the trachea and 5 mm in the bronchi is commonly applied. Low-dose radiation brachytherapy requires hospitalization, and the typical treatment is one session. Intermediate-dose radiation uses fractions of 200 to 1200 cGy/h, with each session lasting 1 to 4 hours and cumulative total doses similar to low-dose radiation. High-dose radiation delivers more than 1000 to 1200 cGy/h.

With brachytherapy, the delivery catheter can be placed in the upper lobe bronchi and segmental bronchi, areas that are typically inaccessible to laser therapy. Endobronchial radiotherapy also has been used successfully in patients with peribronchial disease, and patients often require less retreatment for disease recurrence. Disadvantages to brachytherapy include intolerance of the catheter; excessive radiation-induced bronchitis; cough; fistula formation between the esophagus, pleura, or great vessels; hemorrhage; and infection. The incidence of hemoptysis appears to be associated with the location of the tumor or site of treatment. Treatment of tumors in the right and left upper lobes carries the highest risk for hemoptysis because of the proximity to the great vessels.

Airway Stents

Techniques and products used for tracheobronchial stent placement are presented in Chapter 49. The first dedicated, completely endoluminal airway stent was introduced by Jean-François Dumon in 1990. Since that time, there have been numerous different designs, each of which exhibits various advantages and disadvantages, which were described previously. The importance of airway stents to this discussion is twofold: the necessity of their use after various endoblative therapies to achieve complete tumor debulking, thus limiting local disease recurrence, and the selection of an appropriate stent for benign versus malignant processes.

There are currently two main types of stents: metal and silicone. Although metal stents are placed easily, they can be extremely difficult to extract. Metal stents are available in covered (typically with Silastic or polyurethane) and uncovered varieties. For malignant airway obstruction, the only appropriate metal stents are covered models, which prevent tumor ingrowth. Silicone stents, on the other hand, require rigid bronchoscopy for placement, but they are removed more easily and are significantly less expensive. The rate of stent migration, however, tends to be higher with silicone stents than with metal stents.

The most commonly used metal stents are made from nitinol. Nitinol is a superelastic biomaterial that has the ability to undergo great deformations in size and shape. In addition, nitinol has “shape memory”; that is, at cold temperatures, the stent is easily deformable, and at higher temperatures (i.e., body temperature), it regains its original shape. The risk of airway perforation seems to be lower with nitinol stents because they do not change length once expanded and are flexible enough to change shape with a cough yet have excellent radial strength during constant compression by tumor or stenoses. Nonmetallic stents generally are made from molded silicone and are shaped to prevent migration or contain polyester wire mesh embedded in silicone. Dynamic stents contain metal struts embedded in silicone and are Y-shaped. Silicone stents are commonly placed with the aid of a specially designed stent introducer system in which the stents are preloaded into the introducer and inserted into the stricture with the aid of a stent pusher. The Dumon stent is currently the most widely used stent throughout the world, and some feel that it is the “gold standard” against which future stents will have to be compared.

It is not clear whether stenting may be beneficial for some or all cases of tracheobronchial malacia with symptoms of airway obstruction. The dynamic characteristics of tracheobronchial malacia are quite different from those of static causes of CAO, and therefore, the forces placed on the stents are also different. The shape of the airway in patients with tracheobronchial malacia is different from the normal trachea and also different from the typical cylindrical shape of most stents, thus altering the surface contact dynamics between the stent and airway.

It is crucial that the indications for stent placement are clear, that the appropriate stent is selected, that an endoscopist with significant experience inserts the stent, and that the patient is provided with appropriate education and follow-up. Especially in cases of benign CAO, a metal stent should be placed only when no other therapeutic options, including surgical correction, are available.

All patients with a history of airway obstruction should carry a card or bracelet identifying them as patients with complicated airways or indwelling airway stents. The presence of a complicated airway, however, does not preclude intubation, if needed. On completion of the procedure used to ablate a malignant obstruction, most patients can be extubated. For patients who experienced respiratory failure for some time prior to the intervention and have limited pulmonary reserve, a brief period of positive-pressure ventilation may be required.

Readers are referred to Chapter 54 for a description of rigid and flexible bronchoscopic techniques. Virtually any technique can be used effectively for endobronchial therapy, provided that the user is experienced.

Close follow-up of all patients is indicated to identify problems at an early stage. Potential complications include stent migration, airway occlusion by secretions, accumulation of necrotic tissue or granulation tissue, infection, and recurrence of the obstruction caused by progression of the underlying disease. Patients therefore must be educated about symptoms that should prompt further investigation.

CAO caused by endobronchial lesions may be extrinsic, intrinsic, or mixed; fixed or dynamic; and benign or malignant. Patients with CAO present with a number of symptoms ranging from mild shortness of breath to respiratory failure. In the decompensated patient, it is of vital important to restore oxygenation and ventilation immediately. Further interventions are based on the nature of the obstruction, quality-of-life issues, available techniques, and physician expertise. Almost any technique can achieve the desired results if performed by an experienced bronchoscopist.²³ The endoscopic management of CAO can provide successful palliation in over 90% of patients.²⁴ Often the best therapy includes a combination of several treatment approaches. Interventions should be chosen that leave open other options for further therapy. Although it is essential for all pulmonary and critical care physicians and surgeons to be educated about the diagnosis and initial management of CAO, the most comprehensive assessment and therapy generally are provided by centers with a multidisciplinary airway team that specializes in the management of patients with compromised airways.

Examples of clinical scenarios necessitating urgent bronchoscopic intervention are presented along with several therapeutic or palliative strategies for managing the underlying disease process. Infectious and neoplastic processes (benign or malignant) causing airway constriction (<5 mm luminal diameter) account for the majority of emergent CAOs (Figs. 67-2 and 67-3).

Endobronchial surgery with electrocautery is used for definitive resection of a benign hamartoma (Fig. 67-3B,C). Photodynamic therapy (Fig. 67-4) is delivered to a patient with a CAO secondary to non–small-cell lung cancer.

After relief of the emergent CAO, a patient with a post lung transplant stenosis in the right mainstem, bronchus is implanted with an expanding metal stent (Figs. 67-5 and 67-6).

Although there are multiple endobronchial techniques for managing tumors that involve the central airways, there are no prospective randomized studies that compare the various treatment strategies. Hence, the specific treatment used for each patient depends on the expertise of the treating physician and available equipment. It is important to consider the simple oncologic principles while treating patients. The first objective is to establish airway patency, the second to establish local control, and the third systemic control. For best long-term results, it is usually necessary to combine multiple modalities.