The incidence of lung cancer in the United States exceeds 200,000 new cases/y, with over 150,000 deaths attributable to this malignancy per year.1 Given the potential benefit of the diagnosis and treatment of lung cancer at an early stage, evaluation of the solitary pulmonary nodules represents an important and major part of the general pulmonologist’s practice. There are new data on the utility of low-dose helical computed tomography (CT) in reducing mortality in lung cancer by screening, and it is likely that the need for diagnosis of the solitary pulmonary nodule will increase.2 Current guidelines recommend further diagnostic evaluation for a solitary pulmonary nodule >8 mm in diameter in high-risk patients.3
The sensitivity of fiberoptic bronchoscopy in the diagnosis of endobronchial pulmonary abnormalities is very good, approaching 90%.4 However, in small and peripheral lung lesions, the sensitivity of fiberoptic bronchoscopy is much worse, approximately 14%.5 In peripheral solitary pulmonary nodules, other potential diagnostic modalities include CT-guided biopsy and surgical biopsy, although both of these procedures have associated risks.6–9
Electromagnetic navigation bronchoscopy (ENB) is a relatively new technology that is intended to direct bronchoscopic biopsy tools to peripheral lung lesions. The components of this system include an electromagnetic location board, a disposable locatable guide that contains a location sensor at its distal tip and allows 360-degree steerability through the bronchial tree, an extended working channel (EWC) that becomes a channel for endobronchial tools, and software for navigation and planning that produces a 3-dimensional reconstruction of the bronchial airways from CT scans.
To date, only a handful of studies have been performed to evaluate the utility of ENB.10–19 We sought to further characterize the accuracy rates and rates of complications by a retrospective review of all ENB procedures performed at our facility since its acquisition in 2008.
PATIENTS AND METHODS
A retrospective cohort review of all ENB procedures performed at this institution was performed. Data were collected on patients who underwent ENB from November 11, 2008 until July 1, 2011 at the University of Kansas Medical Center (Kansas City, KS). The study was approved by the local Institutional Review Board (HSC #12471).
All patients chosen to undergo ENB were at the discretion of the 3 attending physicians performing the procedure at this institution. In all of the selected patients, the reason for performing ENB included a solitary pulmonary nodule, pulmonary infiltrate, or hilar lymphadenopathy that was not considered to be accessible by conventional bronchoscopy. The proceduralist performed all of the preprocedure software planning with the associated labeling of targets and virtual reference points to guide the placement of the EWC. The patients who underwent ENB were older than 18 years of age and gave informed consent before the procedure was initiated.
The primary endpoint measured was diagnostic yield. If the ENB-directed biopsy yielded a plausible histologic diagnosis, then the ENB was considered successful. If the ENB-directed biopsy result was nondiagnostic or negative for malignancy, then an additional procedure was carried out. Such additional procedures were a CT-guided transthoracic needle aspiration, surgical biopsy, or serial CT scans. If the additional procedure confirmed the diagnosis from ENB, such as a surgical lung biopsy showing no malignancy or serial CT scans showing no growth, then the ENB was considered a success. If the ENB-directed biopsy was nondiagnostic and the additional procedures revealed an alternative diagnosis, then ENB was considered a failure.
Other data collected were the rate of complications, standard uptake value on positron emission tomography scan if performed, lesion size and location, presence or absence of a bronchus sign, distance of the lesion from the pleura and hilum, spirometry, smoking status, malignancy history, and history of immunosuppresion. Lesion location was further defined as being central, intermediate, or peripheral, as has been previously described.5 The area surrounding the hilum on CT scan was divided into 3 elliptical regions: abnormalities in the inner third were considered central, abnormalities in the middle third were considered intermediate, and abnormalities in the outer third were considered peripheral. If the abnormality overlapped into >1 elliptical region, it was assigned to the region in which the majority of its area was contained.
All patients undergoing ENB had a preprocedure CT examination of the thorax. The navigation software used required a slice thickness of 1.25 mm and slice intervals of 1 mm (with an overlap of 0.25 mm). The CT scan dicom images were imported into the software (superDimension) during the initial planning phase by the proceduralist. Virtual reference points were selected by identifying at least 5 anatomic landmarks (typically the carina of the individual lobes), in addition to the target lesion itself.
The same ENB system (superDimension; superDimension Inc., Plymouth, MN) was used for each procedure. All patients underwent endotracheal intubation with general anesthesia before procedural initiation. Bronchoscopy was performed using an adult therapeutic bronchoscope (Model numbers BF-1T180 and BF-P180; Olympus, Tokyo, Japan), with a 2.8- or a 3.2-mm working channel. Endobronchial mapping was then performed using the previously identified virtual reference points and linking them to actual positions within the endobronchial tree. The software (I-Logic version 6.2.29; superDimension Inc.) then determined the variance, which is defined as the apparent difference in the location of the steerable probe in the actual patient from the anticipated location in the virtual patient. A variance of <7 mm was required before proceeding with the procedure.
Once mapping was completed, the bronchoscope was wedged into the navigated bronchial subsegment and the sensor probe with the EWC was advanced to the target lesion using the virtual images. Once the EWC was in the proper location, specimens were obtained through the EWC using biopsy forceps, brushing, transbronchial needle aspiration, and/or washing, all carried out at the discretion of the performing physician. Fluoroscopy was used in all cases to ensure that the instruments did not dislodge the EWC and to confirm placement of biopsy tools relative to the lesion and the pleural surface. Rapid on-site cytopathologic evaluation (ROSE) was also used to ensure that adequate specimens were collected. All patients underwent a postprocedure chest radiograph to exclude an iatrogenic pneumothorax.
Statistical analysis was performed using a statistical software program (GraphPad Prism 5; GraphPad Software Inc., La Jolla, CA). Proportions were compared using the Fisher exact test or a 1-sided χ2 test where appropriate. A P-value of <0.05 was used to indicate statistical significance.
A total of 55 patients underwent ENB between November 4, 2008 and June 28, 2011. The patient characteristics are shown in Table 1. The median lesion size was 2.75 cm (range, 1.1 to 7.8 cm). Thirty-seven of the 55 patients underwent positron emission tomography scanning within 1 month of the procedure being performed, with an average standard uptake value of 9.06 (range, 1.94 to 26.32). The majority of the pulmonary lesions were located in the upper lobes, with 13/55 in the right upper lobe and 21/55 in the left upper lobe. The rest of the lesions were distributed among the right middle lobe, right lower lobe, left lower lobe, and right hilar area (5/55, 10/55, 4/55, and 2/55). Lesions were further characterized by their location as being central, intermediate, or peripheral. Fifteen lesions were defined as being central (27.3%), 26 lesions were intermediate (47.3%), and 14 lesions were peripheral (25.4%).
Of the 55 ENB procedures performed, 41 were considered diagnostic: 25 revealed a carcinoma, 13 showed no evidence of malignancy that was confirmed by another diagnostic test, and 3 revealed infection (Table 2). This led to a diagnostic yield of 74.5%. Of the nondiagnostic studies, 11 were found to be malignant after additional studies, 1 was found to be a foreign body, 1 was found to represent a noncaseating granuloma, and 1 patient had hospice care for her known head and neck carcinoma and had no further testing performed (Table 3). Of the 36 malignancies eventually diagnosed in this cohort of patients, 25 were detected with ENB, yielding a sensitivity of 69.4% for malignancy. The positive predictive value with ENB for malignancy was 100%, whereas the negative predictive value for malignancy was 63.3%. However, when ENB failed to reveal a diagnosis, the negative predictive value for malignancy was 54.2%, that is, when alternative benign diagnoses such as infection were excluded from the analysis.
Of the 36 patients with an eventual diagnosis of a malignancy, 11 were diagnosed after a nondiagnostic ENB: 6 through CT-guided transthoracic needle aspiration, 3 through surgical lung resection, 1 through endobronchial ultrasound, and 1 through mediastinoscopy. Of those 11 patients, 5 underwent surgical resection with a curative intent. Of the 25 patients whose malignancy was diagnosed by ENB, only 5 subsequently underwent surgical resection with a curative intent.
Of the 31 patients with a positive bronchus sign, 25 had diagnostic ENB (80.6%). Of the 24 patients with negative bronchus sign, 16 had diagnostic ENB (66.7%), yielding a P-value of 0.35. Table 4 shows the diagnostic yield by specific location of the lesion. No significant difference was seen in the yield from any specific lobe of the lungs (P=0.22). We did observe a nonsignificant increased yield in lesions <3 cm in diameter compared with lesions >3 cm in diameter (P=0.22). Table 5 further examines the different subgroups. We did find a nonstatistically significant increase in yield in lesions that were central and intermediate over peripheral lesions (P=0.15). No further statistical significance was observed between the different subgroups.
We found that the success rates with ENB did correlate with experience with the procedure, although there was no statistical significance. At our institution, 3 physicians performed ENB, and the proceduralist with the most experience also had the highest success rate (26/32 or 81.3%). The other 2 proceduralists had lower success rates (12/17 or 70.6% and 3/6 or 50%), P-value of 0.24. Similarly, we found that in each subsequent year of having ENB, we experienced a trend toward higher success rates. In 2009, we had a diagnostic yield of 63.6% (14/22 cases were successful), which increased to 72.2% in 2010 (13/18 cases were successful) and to 90% in 2011 (9/10 cases were successful), with a P-value of 0.31.
There were no postprocedure pneumothoraxes in patients undergoing ENB. In addition, there were no cases of excessive bleeding. There were 2 cases of postprocedural hypoxemic respiratory failure, one of which required admission to the hospital for 3 days, the other of which required reintubation and mechanical ventilation in the intensive care unit. Both patients were eventually discharged home from the hospital and had no further repercussions from the procedure.
In this study, we demonstrated that ENB can be performed safely and with a high success rate to diagnose pulmonary lesions that would not be amenable to conventional bronchoscopy. Our approach to ENB does differ from that which has been previously published.
At our institution, all patients undergoing ENB have general anesthesia with endotracheal intubation. Previous studies of ENB provide no consensus regarding whether general anesthesia or conscious sedation is the preferred means of procedural sedation. It has been our experience that given the longer procedural time for ENB, compared with conventional bronchoscopy, patients tolerate ENB better with general anesthesia. In addition, general anesthesia inhibits the cough reflex and may enable easier navigation to the target lesion. No publications compare the routine use of general anesthesia versus conscious sedation in standard fiberoptic bronchoscopy.
We used mobile C-arm fluoroscopy in all ENB. As with anesthesia, previously published studies disagree regarding the use of fluoroscopy with ENB. One study did conclude that ENB could be safely performed without the need for fluoroscopy.14 This study demonstrated a diagnostic yield of 67% and no increase in the rate of pneumothorax. We have observed that the use of fluoroscopy is helpful in excluding the peripheral placement of biopsy forceps and confirming the proper positioning of the EWC, which may become dislodged during the manipulation of biopsy tools. Furthermore, given that the fluoroscopy time per case at our institution is <120 seconds in duration (data not shown), this represents a relatively small amount of radiation exposure, far less than the radiation received with a routine CT of the chest.20 In addition, we had no cases of postprocedural pneumothorax in our cohort of patients. Table 6 shows the differences in the procedural details of the previous studies of ENB and their associated diagnostic yield.
All ENB procedures were performed with the availability of ROSE. ROSE has been shown to improve the yield of transbronchial aspirates and leads to fewer biopsies.21,22 It is also cost-effective as it allows for saving of additional and unnecessary disposable diagnostic tools, which exceeds the cost of having on-site cytology available.23 ROSE is helpful in providing further confirmation that the EWC has been positioned in the correct location and that the tissue being sampled is diagnostic.
With regard to our diagnostic yield, we found ENB to be highly specific for the diagnosis of malignancy, although the negative predictive value of 54.2% for malignancy was noted when a plausible diagnosis was not obtained through ENB (ie, malignancy or infection). Therefore, we recommend that a negative ENB study should not be used to exclude malignancy and instead suggest that any negative ENB study be followed with another diagnostic test.
Our study failed to confirm previous studies that showed the utility of the bronchus sign in improving the diagnostic yield with ENB.18 We found that the presence of a positive bronchus sign was associated with a 13.9% absolute increase in the diagnostic yield with ENB, although our small sample size gave us a power of 0.23 to detect significance for these group sizes. Also, our inability to show statistical significance may be due to our higher success rate of ENB in patients without a bronchus sign (16 of 24 patients with diagnostic studies), compared with the previous study’s lower success rate in patients without a bronchus sign (4 of 13 patients with diagnostic studies). We suspect that the use of fluoroscopy in ENB, which was not used in the previous study, may improve the yield when the bronchus sign is absent.
In addition, we found that there was a trend toward an improved yield in lesions located in a central or an intermediate location compared with lesions located in the outer third of the lungs. We found a nonsignificant trend toward an improved diagnostic yield in lesions <3 cm in diameter. Because of the low yields of larger peripheral lesions that we observed in this study, it is important to consider transthoracic needle aspiration as a potential modality to obtain a diagnosis, when appropriate.
We found no correlation between lesion size and procedural experience, with regard to the diagnostic yield. There was a nonsignificant trend toward an improved diagnostic yield with increased user experience, which has not been demonstrated previously. However, we have observed anecdotally that the number of endobronchial turns with the EWC needed to navigate toward the target lesion may have more impact on the diagnostic yield than lesion size or location. These data were not systematically recorded and provide an avenue for further study.
Our study has several strengths, including the large number of patients with a variety of clinical conditions, excellent patient follow-up, and inclusion of data from all patients undergoing ENB. In addition, no support was requested or received from the company that produces ENB, and this study was performed without their knowledge. Our limitations include the retrospective nature of our study and the nonuniform protocol for following biopsy-negative lesions. In addition, procedural time and navigation error were not recorded.
In summary, we have shown that ENB can be performed with a diagnostic yield of 74.5% and a low complication rate. This diagnostic yield is among the highest that has been reported and may be related to our use of fluoroscopy, general anesthesia, and ROSE during ENB.
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Keywords:© 2012 Lippincott Williams & Wilkins, Inc.
electromagnetic navigation bronchoscopy; peripheral lung lesion; pulmonary nodule; transbronchial lung biopsy