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(Chest. 2001;119:781-787.)
© 2001 American College of Chest Physicians

Endobronchial Argon Plasma Coagulation for Treatment of Hemoptysis and Neoplastic Airway Obstruction*

Rodolfo C. Morice, MD, FCCP; Turhan Ece, MD; Ferah Ece, MD and Leendert Keus, RPFT

* From the Section of Interventional Pulmonary Medicine, Department of Pulmonary Medicine, The University of Texas M.D. Anderson Cancer Center, Houston, TX.

Correspondence to: Rodolfo C. Morice, MD, FCCP, Section of Interventional Pulmonary Medicine, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Box 76, Houston, TX 77030; e-mail: rmorice{at}mdanderson.org


   Abstract
TOP
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 References
 
Study objective: To evaluate the usefulness of endobronchial argon plasma coagulation (APC) for the treatment of hemoptysis and neoplastic airway obstruction.

Design: Retrospective study.

Setting: Bronchoscopy unit of a university hospital.

Patients: A total of 60 patients with bronchogenic carcinoma (n = 43), metastatic tumors affecting the bronchi (n = 14), or benign bronchial disease (n = 3). Indications for intervention were hemoptysis (n = 31), symptomatic airway obstruction (n = 14), and both obstruction and hemoptysis (n = 25). Hemoptysis was stratified as a volume of > 200 mL/d (n = 6), > 50 to 200 mL/d (n = 23), or <= 50 mL/d but persistence for > 1 week (n = 27). The mean (± SD) duration of hemoptysis was 16.5 ± 16.1 days before intervention. Obstruction sites were the trachea (n = 8), mainstem bronchi (n = 21), and lobar bronchi (n = 30). In 24 cases, the patient had obstructions at multiple sites. The mean size of the pretreatment obstruction was 76 ± 24.9%.

Interventions: APC, a noncontact form of electrocoagulation, was performed via flexible bronchoscopy. Sixty patients underwent 70 procedures. Conscious sedation without endotracheal intubation was used in all patients except four, who were mechanically ventilated because of underlying respiratory failure.

Measurements and results: All patients with hemoptysis experienced a resolution of bleeding immediately after APC. Hemoptysis from treated sites did not recur during a mean follow-up duration of 97 ± 91.9 days. Patients with endoluminal airway lesions had an overall decrease in mean obstruction size to 18.4 ± 22.1%. All patients with obstructive lesions, except one who died of sepsis, experienced symptom improvement. In these patients, symptom control was maintained during a median follow-up period of 53 days (range, 18 to 321 days). There were no complications related to the procedure.

Conclusions: APC is effective for the treatment of endoluminal hemoptysis and airway obstruction. The procedure can be performed in an outpatient setting or at the bedside in the ICUs. APC provides a simpler, lower-risk alternative to other interventional endobronchial techniques.

Key Words: airway obstruction • argon plasma coagulation • bronchial neoplasms • bronchoscopy • electrocoagulation • endobronchial therapy • hemoptysis


   Introduction
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 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 References
 
Neoplastic airway invasion is common among patients with lung cancer and metastatic malignancies.1 2 These patients may present with symptoms caused by tracheobronchial tumor extension, such as dyspnea, bleeding, intractable cough, and postobstructive pneumonia. In selected cases, bronchoscopic interventions can prevent imminent death, offer clinical stability that will allow additional cancer treatment, or palliate symptoms.3 Endobronchial therapies can also be curative in some patients with early-stage malignancies4 or benign airway disease.5

Technical developments in the past 20 years have generated multiple types of bronchoscopic treatments.6 7 8 9 A significant portion of these techniques, however, have been out of the reach of most clinical bronchoscopists. High equipment costs, scarcities of training resources, cumbersome instrumentation, and operational safety concerns have prevented a more general utilization of these technologic advances.

Argon plasma coagulation (APC) is a form of noncontact electrocoagulation. It offers the simplicity and low cost of an electrocoagulator with the noncontact approach of an Nd-YAG laser. The noncontact feature of APC allows rapid coagulation with minimal manipulation of and mechanical trauma to the target tissue. The term plasma is used to describe an electrically conducting medium produced when the atoms in a gas become ionized. It is sometimes referred to as the fourth state of matter, distinct from the solid, liquid, and gaseous states. APC utilizes electrically conductive argon plasma as a medium to deliver high-frequency current via a flexible probe. The argon plasma flow transfers electricity between the probe and the target tissue (Fig 1 ). The basic APC system is composed of an argon gas source, a computer-controlled high-frequency electrosurgical generator, and the endoscopic probe (Fig 2 ). Tracheobronchial access is obtained by passing the probe through the working channel of the bronchoscope.



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  		Figure 1.. Schematic representation of a section of the APC probe and electrically conductive gas (argon plasma) interacting with the target tissue. The electrode within the APC probe ionizes the argon gas, allowing noncontact flow of electrical current between the probe and the tissue. The argon plasma beam acts not only in a straight line, along the axis of the probe, but also laterally, as shown in this diagram. On arrival to the tissue, the application of energy causes uniform zones of desiccation (A), coagulation (B), and devitalization (C) in the areas receiving treatment.

 


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  		Figure 2.. Photographic depiction of the APC equipment (ERBE USA Inc). The upper component is an electrosurgical unit (ERBOTOM ICC 200) that generates the high-frequency voltage required to power the APC unit located immediately below (APC 300). The electrosurgical unit can be used independently of the APC, allowing the option of using standard electrocautery snares and probes in combination with APC.

 
The usefulness of APC has been documented in numerous studies of hemostasis and ablation of lesions in GI endoscopy.10 11 Publications in the field of otolaryngology have reported the effectiveness of APC for the treatment of epistaxis12 and upper airway papillomatosis.13 We studied the effectiveness of APC in therapeutic bronchoscopy for patients with hemoptysis and/or symptomatic endoluminal airway obstruction. We also studied the feasibility of using this technique through the flexible bronchoscope in the bronchoscopy suite or as a bedside procedure in ICUs.


   Materials and Methods
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 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 References
 
For this study, endobronchial therapy with APC was indicated for patients with hemoptysis or symptomatic endoluminal airway obstruction. Patients with hemoptysis were eligible for this study if they met all of the following criteria: (1) bleeding originated within the tracheobronchial tree; (2) the site of bleeding was identifiable during flexible bronchoscopy; and (3) there was an absence of coagulopathy or other medically correctable causes of hemoptysis. Patients with obstructing airway neoplasms were included in this study if they met all of the following criteria: (1) symptoms were related primarily to airway obstruction and not to systemic disease; (2) the tumor was located within the lumen of the airway; (3) the margins between tumor and normal airway were identifiable; (4) tumor length was <= 3.5 cm; and (5) there was functional lung distal to the obstruction or relief of postobstructive pneumonia was feasible.

All endobronchial APC procedures were performed with a flexible bronchoscope. Except in those patients who required mechanical ventilation because of respiratory failure owing to their underlying disease, all procedures were performed transnasally or transorally in the bronchoscopy suite. Local anesthesia and conscious sedation with IV midazolam and fentanyl were administered before and during the procedure. Oxygen was supplemented via nasal prongs. Pulse oximetry saturation, BP, and pulse were monitored during bronchoscopy. Patients who were receiving mechanical ventilation in the ICUs underwent endobronchial APC procedures at bedside through an oral-tracheal tube. These patients were already receiving continuous sedation with IV propofol and/or midazolam as part of critical-care sedation protocols for patients receiving mechanical ventilation.

Endobronchial APC was performed with an argon plasma coagulator unit (APC 300 and ERBOTOM ICC 200; ERBE USA Inc; Marietta, GA) via a flexible bronchoscope (model BF-1T10; Olympus America Inc; Melville, NY). Energy at 30 to 40 W and argon flow at 1.6 L/min were applied through a 2.3-mm diameter, 220-cm length APC monopolar probe. The probe was inserted through the working channel of the bronchoscope. The target tissue was endoscopically visualized and then coagulated, and the devitalized tissue was mechanically removed with grasping forceps. Patients who had incomplete lesion debulking after one treatment or who developed evidence of endobronchial mucus plugging underwent a second bronchoscopic procedure for removal of devitalized tissue after 48 to 72 h. Additional endobronchial APC treatments were performed on patients who met study entry criteria if they developed recurrent or new airway disease. Patients who had residual or additional disease not amenable to further APC interventions were considered for other forms of local or systemic therapy. Patients who had APC treatments for benign lesions were followed up with surveillance bronchoscopy 3 months after therapy and as clinically indicated.

Patients’ demographic characteristics, underlying diagnoses, severity and duration of hemoptysis and/or dyspnea, and clinical or roentgenographic manifestations of obstruction or infection were recorded. The location of the airway lesions, the degree of obstruction, the immediate response to therapy, and any complications were documented at the completion of the endobronchial therapy session. The percentage of airway obstruction was estimated by visual comparison between the area of stenosis and the healthy proximal airway. Improvement of dyspnea after APC therapy was classified as excellent if, based on patients’ estimations, the dyspnea resolved or was at least reversed to the level of the dyspnea present before the onset of the airway obstruction. Improvement was classified as moderate if the dyspnea improved without complete resolution and the improvement was less than it existed before the onset of airway obstruction. After bronchoscopic interventions, patients’ outcomes were monitored at 24 h and thereafter as clinically indicated (median, 22 days; range, 5 to 67 days).


   Results
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 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 References
 
From November 1998 to April 2000, 60 patients underwent 70 endobronchial APC treatments. Patients’ demographic characteristics, diagnoses, and locations of endoluminal airway lesions are shown in Table 1 .


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  		Table 1.. Characteristics of Patients, Diagnoses, and Location of Airway Lesions*

 
Conscious sedation without endotracheal intubation was used in all patients except four, who were receiving mechanical ventilation in the ICUs because of respiratory failure caused by their underlying disease. The first author performed all the bronchoscopic interventions. Fifty-seven treatments (81%) were conducted on ambulatory patients. These patients were discharged home on the day of the procedure after remaining in stable condition during a period of observation in the bronchoscopy recovery area. In the remaining 13 cases, the patients were hospitalized because of their primary clinical conditions. No patient was hospitalized because of the bronchoscopic intervention.

Indications for APC therapy were hemoptysis (31 patients), symptomatic endoluminal airway obstruction (14 patients), and both obstruction and hemoptysis (25 patients) (Table 2 ). The onset of hemoptysis occurred at a mean (± SD) of 16.5 ± 16.1 days before endobronchial intervention. Bleeding was severe (> 200 mL/d) in 6 patients, moderate (> 50 to 200 mL/d) in 23 patients, and mild (<= 50 mL/d) but persistent for > 1 week in 27 patients (mean onset, 19.3 ± 14.1 days). Endoluminal airway bleeding was completely controlled in all patients immediately after APC. No recurrence of hemoptysis from a treated site was noted during a mean follow-up period of 97 ± 91.9 days. Three patients were treated with APC for a second episode of hemoptysis that originated from a new endobronchial site at 53, 87, and 101 days after the initial treatment. One patient required arterial embolization after APC for management of bleeding that originated from a peripheral lung mass beyond the reach of the bronchoscope. Except for two patients who had benign conditions, all patients with hemoptysis had malignant diseases. Bleeding from benign lesions occurred in areas of dilated vascular proliferation and bronchiectasis associated with prior external-beam irradiation.


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  		Table 2.. Indications for APC Therapy and Patients’ Manifestations of Endoluminal Airways Disease*

 
In the group of patients who had symptomatic obstruction, the endoluminal airway lesions were located in the trachea in 8 cases, in the mainstem bronchi in 21 cases, and in the lobar bronchi in 30 cases. In 24 of these cases, the patient had an obstruction at more than one site. Except for one patient who had a symptomatic bronchial web-like stenosis, all patients with bronchial obstruction had malignant disease. Patients with endoluminal masses had a pretreatment reduction of the healthy airway lumen that averaged 76 ± 24.9%. Immediately after APC and mechanical debulking, the obstruction decreased an average of 26 ± 30.5%. Seven patients required an additional bronchoscopic procedure for the removal of devitalized tissue 48 to 72 h after the initial APC treatment. This second intervention further decreased the overall posttreatment bronchial obstruction to a mean value of 18.4 ± 22.1% (Fig 3 ). There were no complications directly related to endobronchial therapy.



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  		Figure 3.. Diagram indicating the degree of endoluminal obstruction before treatment (left, A) and after treatment (right, B). Values are presented as the mean percent reduction of the healthy airway lumen. The numbers correspond to 1 SD of the mean values.

 
Symptoms improved immediately after tumor destruction in all patients except for one, a patient who was receiving mechanical ventilation who died within 48 h owing to neutropenic sepsis and underlying pneumonia. Improvement of dyspnea immediately after endobronchial tumor debulking was excellent in 37 cases (53%) and moderate in 32 cases (46%) (Fig 4 ). Two patients underwent a second APC intervention for mechanical debulking of recurrent endoluminal obstruction 149 and 210 days after the initial treatment. Twenty-one patients also received high-dose-rate endobronchial brachytherapy after APC for a boosting effect or ablation of the residual tumor. Relief of dyspnea related to obstruction was maintained for a median follow-up period of 53 days (range, 18 to 321 days).



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  		Figure 4.. An example of tumor debulking using APC for the treatment of an airway obstruction in a patient with non-small cell carcinoma. Top left, A: a pretreatment endoscopic examination shows an 80% occlusion of the distal trachea by an endoluminal mass. This tumor originated in the right upper lobe and extended through the right mainstem bronchus into the trachea. Top right, B: a pretreatment flow-volume loop tracing that is indicative of a severe, fixed central airway obstruction. Bottom left, C: a complete reopening of the trachea and right mainstem bronchus immediately after APC and tumor removal. Bottom right, D: normalization of the flow-volume loop tracing 48 h after bronchoscopic intervention.

 

   Discussion
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
References
 
APC has been used for > 10 years in open surgery,14 laparoscopy,15 and GI endoscopy.16 This is the first study (to our knowledge) that reports on the feasibility and effectiveness of APC for hemostasis and debulking of endoluminal tracheobronchial lesions through the flexible bronchoscope. The excellent safety profile, readiness of use, and relatively low cost make APC most suitable for therapeutic applications through the flexible bronchoscope in the outpatient setting. This study also attests to the operational simplicity and portability of equipment that allows expansion of the range of therapeutic interventions to bedside use in the ICUs. The noncontact approach offers advantages over other forms of electrocoagulation. Avoiding tissue contact and probe adhesion to friable tissues decreases the risk of bleeding. It also allows the bronchoscopist to treat a larger area very quickly.

Proper patient selection for therapy with endobronchial APC is crucial. For patients with hemoptysis, the bleeding source must be endobronchial and within the reach of the bronchoscope for APC to be effective. Patients with severe bleeding and respiratory compromise should be stabilized before any intervention. Endobronchial therapy in these patients is aimed at preventing recurrence once the acute episode of massive hemoptysis has decreased or subsided. The selection of rigid vs flexible bronchoscopy to assess or treat massive hemoptysis most likely reflects the user’s experience and the clinical circumstances. The rigid bronchoscope allows better suctioning and airway control, while the flexible bronchoscope permits easier access and visualization of distal airways.17 Flexible bronchoscopy was used in all patients enrolled in this study.

The ablation of obstructive airway lesions should be done with the purpose of regaining significant lung function or relieving postobstructive pneumonia. In the absence of postobstructive pneumonia, no benefit from endobronchial therapy will be gained if the lung distal to the obstruction is nonfunctional, for example in patients with extensive parenchymal tumor invasion or postradiation fibrosis. Patients selected for endobronchial APC should have primarily respiratory rather than systemic symptoms of widespread malignancy. Airway lesions that are most suitable for treatment with APC are those measuring <= 3.5 cm in length. To obtain the best results, these tumors should protrude within the lumen and not extend beyond the cartilage of the airway. Ideally, the bronchoscopist would be able to identify the anatomic boundaries of the tumor and appreciate that the airway not involved by tumor is well-preserved. Patients who present with diffuse, concentric malignant infiltration and with significant distortion of anatomic landmarks are best treated with endobronchial brachytherapy.18 Furthermore, obstructions caused by lesions that extrinsically compress the airway are best palliated with external- beam radiation therapy or endoluminal stents.19

Some patients may require a combination of endobronchial therapies. APC can be used to control bleeding before brachytherapy or to reestablish the adequate opening of an occluded airway for subsequent passage of a catheter for brachytherapy. The electroconductive properties of APC make this technique best suited for the removal of a tumor that may have grown over stents without damage to the stent. The latter use has been reported for APC applications in GI endoscopy.20 Our study also documented the usefulness of APC therapy for hemostasis of bleeding associated with benign vascular proliferation in central bronchiectasis and for the ablation of an endoluminal web.

APC devitalizes tissue gradually by producing temperatures that coagulate and desiccate tissue. As the target surface becomes less electrically conductive, APC will automatically seek adjacent tissue with less electrical resistance. This results in a homogenous but limited depth of penetration (approximately 3 mm). Thus, APC offers uniform coagulation and good protection against airway perforation. When debulking tumors with the APC, the visible surface of the mass is sprayed with the argon beam. This decreases the risk of bleeding and causes a variable degree of tumor shrinkage by dehydration. The tumor is removed through sequential cauterization followed by peeling of tissue as it becomes crusted or coagulated. Tissue is removed with a grasping forceps or suction. The extraction of devitalized tissue in large pieces is desirable to shorten the duration of the procedure. Pieces that do not fit through the working channel of the bronchoscope are removed by simultaneously withdrawing the bronchoscope with the tissue attached to the biopsy forceps.

Although the APC is a noncontact method, the bronchoscopist must hold the tip of the probe close to the target tissue, usually within 3 to 5 mm. Because the current follows the path of least resistance, holding the tip of the probe in proximity to the side of the bronchial wall or the lesion will allow current to flow laterally rather than on a straight path. To prevent trauma to friable tissues, the tip of the probe should be extended past the end of the working channel of the bronchoscope only after the target tissue has been properly identified. During procedures performed with the patient under conscious sedation, the bronchoscopist also should anticipate unexpected movement of the target tissue because of the patient’s cough. Use of the APC with a therapeutic channel bronchoscope is recommended to facilitate the suction of secretions, blood, and smoke.

The Nd-YAG laser is another noncontact thermal device. It differs from APC in that it can generate higher temperatures capable of tissue vaporization and deeper penetration. In combination with rigid bronchoscopy under general anesthesia, the Nd-YAG laser has been the method used most often for the rapid removal of large tumors.21 Although it offers less penetration, the argon plasma beam has the advantage of not having to follow a straight path like the Nd-YAG laser. Because APC seeks electroconductive areas, it can more easily access targets located laterally, radially, or around anatomic corners. APC also does not generate a direct thermal reaction with airway devices that do not conduct electricity. Thus, the risks of igniting endotracheal tubes or other airway catheters are much lower with APC than with the Nd-YAG laser.22 Similarly, the known risk of Nd-YAG laser-induced retinal injury to the operator and technical personnel 23 does not exist during APC instrumentation.

Despite the safety features of APC, care must be taken to reduce risks inherent to any thermal device. The APC probe should extend 0.5 to 1.0 cm beyond the tip of the bronchoscope to avoid collateral thermal damage to the bronchoscope. Supplemental oxygen should be kept at the minimum safe level. In general, maintaining inspired concentration of supplemental oxygen at <= 40%, or intermittently reducing it to this level, is recommended during APC application. No fires or technical complications occurred during the interventions reported in this study. There have been isolated case reports of intestinal wall emphysema and pneumoperitoneum after APC in GI endoscopy.24 Systemic air embolisms have also been reported during bronchoscopic Nd-YAG laser interventions.25 In our patients, we did not observe gas exchange impairment, bronchopulmonary barotrauma, or clinical manifestations of gas embolism associated with the introduction of low-flow, inert argon gas into the airway.

Patient selection for endobronchial tumor ablation with APC requires the understanding that the mere presence of endobronchial disease does not in itself constitute an indication for endobronchial therapy. Standard surgical, medical, and radiation treatments remain the primary therapeutic modalities for patients with bronchopulmonary malignancies. Interventional bronchoscopy must be contemplated in the context of multidisciplinary management of these patients. Procedures such as APC that can be performed in an outpatient setting or at the bedside in the ICUs augment the therapeutic options available to the clinical bronchoscopist. These techniques help to transform the traditional role of the pulmonologist from diagnostic bronchoscopist to active participant in cancer therapy within multidisciplinary programs.


   Footnotes
 
Abbreviations: APC = argon plasma coagulation

Supported by the Mary L.E. McConnell Fund for Lung Research.

Received for publication June 14, 2000. Accepted for publication October 11, 2000.


   References
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 

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