Mahajan, Amit K. MD; Patel, Shruti MD; Hogarth, Douglas Kyle MD, FACCP; Wightman, Rachel BSc
Purpose : The purpose of this study was to investigate the diagnostic yield and safety of electromagnetic navigation bronchoscopy (ENB) on peripheral lung lesions deemed otherwise unreachable using conventional bronchoscopy in high-risk patients.
Methods : This was a retrospective chart review involving adults (age, 18 y and older) who underwent ENB for pulmonary lesions located at the fourth order of bronchi or beyond, including subpleural lesions, at the University of Chicago Medical Center. Forty-eight patients underwent ENB by 3 different trained operators from January 2006 to September 2008. There was a short period of inactivity when the device was withdrawn from the market. ENB was reserved for use only in lesions at the fourth order of bronchi or beyond, including subpleural lesions, in patients who are considered high risk for other invasive procedures. Pathologic, cytologic, and microbiologic studies were carried out on recovered samples. Postprocedural chest radiographs were obtained on all patients to detect the presence of procedure-associated complications.
Results : ENB led to the diagnosis of 37 of 48 (77%) lesions not amenable to conventional bronchoscopic biopsy in high-risk patients. Of the 37 successful procedures, malignancy was identified in 18 patients (49%). Nonsmall cell lung cancer (NSCLC) was diagnosed 16 times, whereas both small cell lung cancer and carcinoid tumor were diagnosed once. In addition, 4 lesions (11%) were found to be infectious, 1 lesion (3%) was found to be granulomatous (noncaseating), and 1 lesion (3%) was diagnosed as organizing pneumonia. Of the 37 successful diagnoses, 13 lesions (35%) were determined to be nonpathologic, benign lesions. Eleven procedures (22%) were unsuccessful in yielding the correct pathologic diagnosis. Nine of the 11 unsuccessful ENB cases (82%) were found to be malignant, 9 of which were identified as NSCLC. Other than NSCLC, 1 neuroendocrine tumor (9%) and 1 metastatic transitional cell carcinoma of the kidney (9%) were identified by alternative, invasive testing methods. The 2 other lesions unsuccessfully diagnosed by ENB were not malignant. One was determined to be infection (histoplasmosis) and the other was diagnosed as an organizing pneumonia. The most common complication noted by all modalities was pneumothorax. ENB carried a pneumothorax rate of 5 of 49 (10%), 2 of which required chest tube insertion for treatment. In the ENB success group, 4 cases (11%) were complicated by pneumothoraces. In the ENB failure group, 1 case (9%) was complicated by a pneumothorax.
Conclusions : ENB is an effective and low-risk modality for diagnosing pulmonary lesions that are difficult to reach in patients deemed to be at high risk for invasive procedures. Although no clear criteria for the use of ENB currently exist, our study shows that diagnostic sampling can be obtained in 77% of lesions at the fourth order of bronchi or beyond, including subpleural lesions.
Clinical Implications : ENB is an effective, minimally invasive method for the diagnosis of pulmonary nodules previously deemed unreachable by conventional bronchoscopy in high-risk patients and harbors a low complication rate.
The bronchoscope is a minimally invasive instrument that can be used to biopsy lung lesions.1,2 Central pulmonary lesions pertaining to malignancy are often biopsied using the flexible bronchoscope. Although the flexible bronchoscope is effective in sampling proximal lung lesions, diagnostic yield from sampling peripheral lung lesions is disappointingly low.3–6 Peripheral lesions in the outer third of the chest that are <2 cm in diameter have a diagnostic yield of only 14% using the conventional flexible bronchoscope.7 Distal airway or pleural-based lung lesions cannot be visualized by the flexible bronchoscope and thus have historically been sampled using computed tomography (CT)-guided needle biopsy. The disadvantage of CT-guided biopsy is the inability to obtain adequate tissue samples for histologic analysis. In addition, transthoracic fine-needle aspiration and video-assisted thoracoscopy (VATS) can be associated with serious complications, especially in patients with poor pulmonary function due to chronic obstructive pulmonary disease.8
Electromagnetic navigation bronchoscopy (ENB) is an image-guided localization procedure that allows the operator to steer a bronchoscope to peripheral lung lesions.4,8 The superDimension inReach system consists of steerable navigation catheters used in concert with navigation software to create virtual 3-dimensional reconstructions of bronchial anatomy. Operators use localization software to maneuver small airways in real time using a virtual bronchoscopic map outlined before the procedure. The objective of this study was to evaluate the diagnostic yield of peripheral pulmonary nodules using ENB in high-risk patients and the rate of complications associated with the procedure.
This was a retrospective chart review involving adults (age, 18 y and older) who underwent ENB for pulmonary lesions located at the fourth order of bronchi or beyond, including subpleural lesions, at the University of Chicago Medical Center. Forty-eight patients underwent elective ENB between January 2006 and September 2008. The Institutional Review Board at the University of Chicago Medical Center approved this study.
ENB was performed on an outpatient basis. Conscious sedation was administered using midazolam, fentanyl, and diphenhydramine. Conventional bronchoscopy was performed for initial airway inspection, followed by ENB using the inReach system (superDimension, Minneapolis, MN). The ENB procedure comprised 3 distinct phases: planning, registration, and navigation. In the planning phase, a previously acquired chest CT scan was uploaded into planning software to create 3-dimensional axial, coronal, and sagittal reconstructions of the patient's airway anatomy. During the registration phase, locatable guide catheters were used with conventional bronchoscopes to mark airway anatomy that correlated with the same positions marked on the previously acquired CT images. During the navigation phase, the patient lay on an electromagnetic field in the bronchoscopy suite. Virtual reconstructed images were adjusted in real time as the locatable guide moved an extended working channel toward the lesion. This was accomplished using technology similar to a global positioning system, but on a smaller, individual scale. The locatable guide was then steered to the peripheral lesion. Standard bronchoscopic sampling instruments were passed through the extended working channel to obtain pathologic specimens.
Specimens were collected during the procedure using transbronchial biopsy, bronchial lavage, or bronchial brushing. The biopsy specimens were obtained under fluoroscopic guidance once navigation was complete, as per company/device protocol. Recovered specimens were analyzed by means of histopathology, cytology, and microbiology immediately after collection. A successful yield using ENB was defined as recovery of tissue or fluid allowing for the diagnosis of malignancy (histologic or cytologic) or infection (bacterial/fungal/acid fast bacilli).
In addition, successful yield by ENB was also acknowledged when ENB biopsy specimens showed no sign of malignancy or infection but did show reactive tissue; further, concurrent follow-up testing (CT-guided needle biopsy, VATS, regression of lesions on follow-up chest CT) convinced the primary physician that the lesion was not malignant or infectious in nature. Failure of ENB was defined by failure of specimens to show malignancy (histologic or cytologic) or infection (bacterial/fungal/acid fast bacilli), but follow-up testing (CT-guided needle biopsy, VATS, progression of lesions on follow-up chest CT) provided objective evidence of malignancy or infection.
Postprocedural chest radiographs were obtained on all patients to identify pneumothoraces incurred secondary to ENB. The presence of pneumothorax or pneumomediastinum was assessed by trained radiologists and confirmed by attending pulmonary and critical care. Postprocedural bronchospasm requiring medical management (continuous albuterol nebulization), hypoxia (oxygen saturation below 90%), and admission to the general medicine service because of complications from the procedure were also recorded.
ENB was performed 49 times on 48 patients between January 2006 and September 2008. Information regarding diagnostic yield, lesion size, lesion location, and complication rates were gathered and analyzed.
Over the course of 21 months, 49 ENB procedures were performed on 48 patients. A diagnosis on radiologic abnormality is yet to be reached in 1 patient who underwent EMN and follow-up radiographic studies.
Of the 48 procedures performed, 37 (77%) yielded tissue samples leading to the correct diagnosis of radiologic abnormality. Eleven ENB procedures yielded tissue samples that failed to diagnose radiologic abnormality, as confirmed by more invasive procedures (CT-guided needle biopsy and VATS) after ENB. Of the 37 successful procedures, malignancy was identified in 18 patients (49%). Nonsmall cell lung cancer (NSCLC) was diagnosed 16 times, whereas small cell lung cancer and carcinoid tumor were diagnosed once. In addition, 4 lesions (11%) were found to be infectious, 1 lesion (3%) was found to be granulomatous (noncaseating), and 1 lesion (3%) was diagnosed as organizing pneumonia. Of the 37 successful diagnoses, 13 lesions (35%) were determined to be nonpathologic, benign lesions. These were confirmed to be nonpathologic by follow-up invasive studies or reduction in size on repeat CT scans.
Of the 48 ENB procedures performed, 11 (22%) were unsuccessful in yielding the correct pathologic diagnosis. Nine of the 11 unsuccessful ENB cases (82%) were found to be malignant, 9 of which were identified as NSCLC. Other than NSCLC, 1 neuroendocrine tumor (9%) and 1 metastatic transitional cell carcinoma of the kidney (9%) were identified by alternative, invasive testing methods. The 2 other lesions unsuccessfully diagnosed by ENB were not malignant; one was determined to be an infection (histoplasmosis) and the other was diagnosed as an organizing pneumonia. The modalities used to diagnose the 11 unsuccessful EMN cases were wedge resection in 4 cases (36%), CT-guided lung biopsy in 5 cases (45%), and CT-guided biopsy of an associated paraspinal mass in 1 case (9%). One patient who underwent ENB unsuccessfully had the procedure repeated and was diagnosed with NSCLC.
During the study, 48 lobes were sampled (Table 1). Within the ENB success group, a total of 37 lobes were sampled. The right upper lobe (RUL) harbored the most targeted lesions and was therefore sampled 14 times (38%). The lobe with the fewest targeted lesions and thus least commonly sampled was the lingual (3%). Within the ENB failure group, a total of 11 lobes were sampled. The RUL harbored the most targeted lesions in the failure group and was unsuccessfully sampled 4 times (36%). The lingual was not targeted (0%) for any of the unsuccessful attempts.
Forty-seven nodules were targeted in this study, but the anterior-posterior (AP) diameter was available for only 46 of these nodules and 1 patient had ENB performed twice on the same nodule. The average AP diameter for all 46 lesions was 2.0 cm, with a standard deviation of ±1.3 cm. Overall, 18 nodules (39%) were >2 cm in AP diameter as observed through preprocedural CT scans, 17 lesions (37%) were between 1 to 2 cm in AP diameter, and 10 lesions (22%) were <1 cm in AP diameter. In the success group, the average AP diameter of 35 lesions was 2.3 cm, with a standard deviation of ±1.4 cm as measured by preprocedural CT scans (Table 2). There was 1 case in which the original CT could not be obtained to determine the size of a nodule. No lesions in the success group were measured as <0.5 cm. In the ENB failure group there were a total of 11 lesions with an average size of 1.2 cm with a standard deviation of ±0.6 cm as measured by preprocedural CT scans (Table 2).
Major complication rates for the ENB and subsequent diagnostic methods were tracked. The most common complication noted was pneumothorax. ENB carried an overall pneumothorax rate of 5 of 49 (10%), 2 of which required chest tube insertion for treatment. In the ENB success group, 4 cases (11%) were complicated by pneumothoraces. In the ENB failure group, 1 case (9%) was complicated by a pneumothorax.
Of the 5 cases that were eventually diagnosed by CT-guided needle biopsy of the lung, 3 procedures (60%) were complicated by pneumothorax (2 requiring chest tubes). All 5 patients who underwent wedge resections were treated with chest tubes, a routine intervention in this procedure. One of the 5 patients (20%) who underwent wedge resection suffered from hypoxia after surgery.
The clinical decision as to which modality should be used in diagnosing peripheral lung lesions must balance the accessibility and complication risk associated with the procedure. Our study shows that ENB is an effective modality for sampling peripheral lung lesions with a high diagnostic yield. In addition, our yield may have been higher considering that CT-to-body divergence may affect outcomes when <4 mm. Peripheral malignancies, notably bronchogenic carcinomas, are common targets for ENB. As these malignancies are often among tobacco smokers, patients often suffer from comorbidities, such as chronic obstructive pulmonary disease and coronary artery disease, which make them poor candidates for invasive diagnostic procedures. Institutions that do not perform ENB require more invasive surgical procedures to sample peripheral lung lesions. These modalities harbor significant risk for procedure-related complications in patients because of the frequency of emphysematous changes in lung parenchyma.9,10 Our study shows that ENB is a safe method to reliably diagnose peripheral lung lesions in patients whose comorbid conditions preclude safe surgical intervention.
The lobe most often associated with ENB success and failure was the RUL. This is likely a result of the difficulty in maneuvering a bronchoscope to the RUL. Attempting to advance the bronchoscope around the acute angles of the RUL is a daunting task when electromagnetic navigation is not used. Although the premise behind the use of ENB is to access peripheral lesions, the size of the lesion is also important. Not surprising, in our study, lesions associated with the highest success rates were lesions with an AP diameter of ≥2 cm, whereas the highest failure rate was with lesions ≤1 cm.
Although our study did show a 10% risk of pneumothorax associated with ENB, transthoracic fine-needle biopsy of pulmonary lesions can be associated with a risk of pneumothorax anywhere from 5% to 64%.11–16
Furthermore, as our institution reserves ENB for those patients deemed to be high-risk surgical candidates, a low complication rate of 10% is considered clinically significant.
ENB has proven to be a beneficial approach for the diagnosis of peripheral lung lesions. ENB provides an avenue for sampling suspicious peripheral lung lesions and offers physicians an alternative to invasive surgical procedures in patients with multiple comorbidities. In addition, recent studies have shown an even greater success of ENB using peripheral-sheath radial ultrasound probes.17 As refinements of bronchoscopic techniques continue to improve and radiographic imaging modalities come online (confocal microscopy, optical coherence tomography), successful biopsy of peripheral lesions should continue to improve. Furthermore, as gene array analysis of tumors continues to improve prognosis and therapy, the need for tissue biopsy, as opposed to fine-needle aspirates, will necessitate more bronchoscopic procedures such as ENB.
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