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CT-guided Needle Biopsy of Small Pulmonary Nodules: Value of Respiratory Gating¹

¹ From the Department of Radiology, Vancouver General Hospital and University of British Columbia, Canada (N.T.); and the Department of Radiology, Osaka University Medical School, 2-2 Yamadaoka, Suita, 565-0871, Japan (N.T., N.M., M.M., T.J., T.K., O.H., S.H., S.Y., H.N.). Received November 3, 1999; revision requested December 10; final revision received March 31, 2000; accepted April 4. Address correspondence to N.T. (e-mail: tomiyama@radiol.med.osaka-u.ac.jp).

	ABSTRACT

TOP ABSTRACT INTRODUCTION Materials and Methods Results Discussion REFERENCES

 
A respiratory gating technique was developed to allow computed tomography–guided needle biopsy of small pulmonary nodules. Twenty-three pulmonary nodules less than 15 mm in diameter underwent biopsy with the use of this technique. There were 14 true-positive, eight true-negative, and one false-negative result (diagnostic accuracy, 96%). The diagnostic accuracy for small nodules without this technique in a historical control was 69% (P < .05).

Index terms: Biopsies, technology, 60.126 • Computed tomography (CT), guidance, 60.12111, 60.12118 • Interventional procedures, technology • Lung, biopsy, 60.126 • Lung, nodule, 60.314, 60.321 • Lung neoplasms, 60.314, 60.321

	INTRODUCTION

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Recent technical advances in computed tomography (CT), such as helical and high-speed scanning, have led to increased rates of detecting small pulmonary nodular lesions (1,2). The distinction of malignant from benign lesions is useful for preoperative diagnosis and treatment planning (3). Although this distinction can often be made with CT-guided needle biopsy, biopsy of small pulmonary lesions may be difficult because of respiratory motion (4). Li et al (5) reported the diagnostic accuracy and sensitivity of CT-guided needle aspiration biopsy of large nodules (>15 mm) as 96% (67 of 70 lesions) and 94%, respectively. The diagnostic accuracy and sensitivity for the biopsy of small nodules (15 mm) were 74% (20 of 27 lesions) and 72%, respectively, a significant difference (P < .05).

The purpose of the current study was to assess the accuracy of CT-guided needle biopsy with the use of a respiratory gating device.

	Materials and Methods

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We prospectively evaluated 23 consecutive CT-guided needle biopsies in 22 patients (in one patient, two separate lesions were sampled), who had pulmonary nodules less than 15 mm in long-axis diameter that were suspicious for cancer and who were advised by physicians to undergo biopsy. From August 1997 to September 1998, all patients underwent biopsy of the nodules with the use of a respiratory gating device. We arbitrarily chose 15 mm as the upper limit for small nodules because larger lesions are usually less technically challenging.

The patients included 11 women and 11 men, with a mean age of 56.2 years (age range, 33–74 years). The nodules were 7.0–15.0 mm in maximum diameter (mean diameter, 12.0 mm ± 2.37 [SD]), and the needle path was 28–100 mm (mean length, 54.2 mm ± 20.6) long. Of the 22 patients referred for diagnostic biopsy, 17 had pulmonary nodules and a known previous or concurrent malignancy (breast malignancy in two patients, hepatic malignancy in three, cervical malignancy in two, gastric malignancy in two, metastatic cerebellar malignancy in one, colonic malignancy in one, laryngeal malignancy in one, renal malignancy in one, and pulmonary malignancy in four). Nodules were in the upper lobe (n = 9), middle lobe and lingula (n = 1), or lower lobe (n = 13). Our study did not include apical nodules, since the movement of such nodules with respiration was expected to be minimal. The institutional review boards approved the study, and informed consent was obtained from all patients.

All patients had initially undergone conventional diagnostic CT (HiSpeed Advantage; GE Medical Systems, Milwaukee, Wis) of the thorax, with 7- or 10-mm-collimated and additional thin-section imaging focused on the nodule, with 1-3-mm collimation that was reconstructed by using a high-spatial-frequency algorithm.

All biopsies were performed by using a ProSpeed scanner (GE Yokogawa Medical Systems, Tokyo, Japan). The patient was placed on the CT table in a supine or prone position, depending on the most likely route for biopsy.

The respiratory gating device was composed of a commercially available respiratory monitor (Autospirometer System 7; Minato Medical Science, Osaka, Japan), an original trigger device, an original amplifier, an original switching unit, and an electric light bulb. After an initial training episode, the patients breathed through a mouthpiece that was connected to the respiratory monitor and experienced no difficulty in doing so. The respiratory curve was displayed in real time (Fig 1). The patients’ functional residual capacity level was recognized during quiet breathing; after that, the operator entered a value of any given desired respired volume greater than the functional residual capacity and activated the trigger device. When the patients’ inspired air volume from functional residual capacity reached the value, a trigger pulse occurred. An original switching unit controlled an electric light bulb, in accordance with the trigger pulse. Subsequently, the patients were instructed to hold their breath when the light bulb illuminated, and a CT scan for the localization of small nodules was obtained. To confirm the location of the nodule, preliminary scans were obtained at a given inspiratory volume. If nodules were initially localized immediately deep to a rib, additional images for localization were obtained at other inspiratory volumes to reposition the nodules away from the rib (Fig 2). The most suitable inspiratory volume, that is, the volume at which the maximum diameter of the lesion was in the intercostal space and there was no major vessel on the biopsy route, was kept constant during subsequent biopsy procedures.

View larger version (15K): [in this window] [in a new window] [Download PPT slide]   Figure 1. Schematic representation of respiratory curve obtained by using a respiratory monitor shows how patients held their breath when the light illuminated (a), and when their inspired air volume from functional residual capacity (b) reached the value that was entered beforehand (c).

View larger version (151K): [in this window] [in a new window] [Download PPT slide]   Figure 2a. A 14-mm-diameter nodule in the superior segment of the left lower lobe of the lung in a 56-year-old man is shown. (a,b) CT scans obtained with the patient in the prone position during CT-guided needle biopsy of the nodule with use of a respiratory gating device. (a) CT scan obtained at the level of inspiration of 1,000 mL above functional residual capacity initially shows the nodule as deep to a rib. (b) CT scan obtained at the level of inspiration of 700 mL above functional residual capacity now shows the nodule as deep to an intercostal space (arrow). Core-needle biopsy revealed metastatic renal cell cancer.

View larger version (152K): [in this window] [in a new window] [Download PPT slide]   Figure 2b. A 14-mm-diameter nodule in the superior segment of the left lower lobe of the lung in a 56-year-old man is shown. (a,b) CT scans obtained with the patient in the prone position during CT-guided needle biopsy of the nodule with use of a respiratory gating device. (a) CT scan obtained at the level of inspiration of 1,000 mL above functional residual capacity initially shows the nodule as deep to a rib. (b) CT scan obtained at the level of inspiration of 700 mL above functional residual capacity now shows the nodule as deep to an intercostal space (arrow). Core-needle biopsy revealed metastatic renal cell cancer.

These data were compared with retrospectively collected data on 13 consecutive CT-guided biopsies of pulmonary nodules smaller than 15 mm without the use of a respiratory gating device that were performed from July 1995 to July 1997. The group of patients who underwent this procedure included nine women and four men, with a mean age of 59.2 years (age range, 46.0–69.0 years). The nodules were 8.0–15.0 mm in maximum diameter (mean diameter, 12.2 mm ± 2.3), and the needle path was 30.0–130.0 mm (mean length, 56.5 mm ± 26.5) long. Nodules were in the upper lobe (n = 6), middle lobe and lingula (n = 1), or lower lobe (n = 6).

In both series, CT-guided biopsies were performed by a resident or fellow (N.M.) under the direction of a staff radiologist, and sampling was performed when a needle tip was demonstrated within the nodule on CT images. The number of passes and complications was recorded. A coaxial technique was used in four CT-guided needle biopsies in which the respiratory gating device was used and in three in which the device was not used. Cytologic examination was performed in all CT-guided needle biopsies. Core-needle (Super-Core; Manan Medical Products, Northbrook, Ill) biopsy was performed in all CT-guided needle biopsies in which the respiratory gating device was used and in seven in which the device was not used. No patient with a negative biopsy result underwent repeat biopsy.

A positive transthoracic needle biopsy result was considered true-positive if there was surgical confirmation, if biopsy of another site revealed cancer or malignancy with the same cytologic and histologic characteristics, or if the patient had a subsequent clinical course consistent with cancer. A negative result was considered true-negative if there was surgical confirmation, if the lesion subsequently disappeared or decreased in size, or if it remained stable for 15 months or more, as seen on follow-up CT scans or chest radiographs.

Diagnostic accuracy was calculated by comparing cytologic or histologic diagnoses based on biopsy findings with final diagnoses based on surgical histologic findings or clinical course. Sensitivity and specificity were calculated for nodules that proved to be malignant at surgery or during the clinical course. Positive and negative predictive values were calculated for nodules with positive and negative results, respectively. The differences in size, needle path length, and location between nodules that underwent biopsy with or without use of the respiratory gating device were assessed by performing the Mann-Whitney test, and the differences in the accuracy, sensitivity, and specificity of biopsy were analyzed by performing the Fisher exact test. A P value of .05 was considered to indicate a significant difference.

	Results

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The mean nodule size, needle path length, and nodule location were similar in both series (in all, P > .05). The mean number of passes per biopsy procedure was two (range, one to three).

There were 15 patients with cancer and seven without, in accordance with the reference standard. One patient with two lesions had cancer and a benign abnormality. CT-guided needle biopsy performed with the use of the respiratory gating device was used to identify 14 patients with a result that was positive for cancer; there were 14 true-positive results, one false-negative result (sensitivity, 93% [14 of 15 lesions]), eight true-negative results, and no false-positive results (specificity, 100% [eight of eight lesions]). The diagnostic accuracy was 96% (22 of 23 lesions). The positive and negative predictive values were 100% (14 of 14 lesions) and 89% (eight of nine lesions), respectively.

The 15 cancers were metastatic renal cell cancer (n = 1), metastatic hepatocellular cancer (n = 1), non–small cell cancer (n = 12), or small cell cancer (n = 1). Of these, 13 were surgically proved. Because a preoperative diagnosis of cancer had already been established at CT-guided needle biopsy, only the false-negative finding required the acquisition of a frozen section during surgery. Two patients, with a diagnosis of small cell lung cancer or metastatic hepatocellular cancer at CT-guided needle biopsy, did not have surgical confirmation. In both patients, follow-up radiologic and clinical findings were consistent with cancer. CT-guided needle biopsy findings were benign in all eight true-negative lesions. In two (25%) patients, CT-guided needle biopsy revealed a specific result: hamartoma in one and fibrosis in one.

Postbiopsy pneumothorax occurred in five (22%) of the 23 CT-guided needle biopsies in which the respiratory gating device was used. Pneumothorax occurred after the final pass in three patients and after the first pass in two. The two patients who had pneumothorax after the first pass had no pulmonary symptoms and underwent insertion of a small drainage catheter during the examination because the nodules shifted from the original location. After drainage catheter insertion, repeat biopsy was performed.

There were 11 patients with cancer and two without, according to the reference standard. CT-guided needle biopsy without use of the device identified seven patients with results that were positive for cancer; there were seven true-positive results, four false-negative results (sensitivity, 64% [seven of 11 lesions]), two true-negative results, and no false-positive results (specificity, 100% [two of two lesions]). The diagnostic accuracy was 69% (nine of 13 lesions). The positive and negative predictive values were 100% (seven of seven lesions) and 33% (two of six lesions), respectively. All 11 cancers were non–small cell cancers; of these, 10 were surgically proved. One patient was subsequently found to have a metastasis, and radiologic and clinical findings were consistent with cancer. Diagnostic accuracy with use of the respiratory gating device was significantly higher than that without use of the device (P < .05). There was no significant difference in sensitivity and specificity between the two groups.

	Discussion

TOP ABSTRACT INTRODUCTION Materials and Methods Results Discussion REFERENCES

 
The use of CT has made it possible to perform biopsy in small pulmonary nodules that are not visible at fluoroscopy (6,7). However, the smaller the lesion, the lower the diagnostic accuracy of needle biopsy (4,5). This decreased diagnostic accuracy is at least in part due to difficulties that are related to respiratory motion. Recently, Connolly and colleagues (8) reported CT-guided needle biopsy of small lung nodules in children. All children were given a general anesthetic, with intubation and controlled respiration. Biopsy was performed at the level of end expiration by disconnecting the ventilator. According to those authors, much of the success of this method was due to the consistency of nodule positioning in the chosen section. When respiration is controlled and the patient is then rendered temporarily apneic, the lungs rest at end expiration. Because this is a relatively constant state close to residual volume or functional residual capacity and is most easily replicated, the investigators chose this as the phase in which to localize the optimum level for biopsy. In our study, it was necessary to change the respiratory level in several patients because the nodules were initially localized immediately deep to a rib.

Wong et al (9) reported active breathing control to reduce radiation therapy margins for organ motion due to breathing in patients with tumors within the thorax and upper part of the abdomen. The apparatus consisted of two pairs of flow monitors and scissor valves, one each to control the inspiration and expiration paths to and from the patient. The patient breathed through a mouthpiece that displayed the changing lung volume in real time. After the patient’s breathing pattern became stable, the operator initiated active breathing control at a preselected phase in the breathing cycle. Both valves were then closed to immobilize breathing motion. The main disadvantage of their system is that it is large and cumbersome to use. We modified a respiratory monitor that is readily available on the market and easy to set and operate.

Recently, Westcott and colleagues (10) reported the accuracy of transthoracic needle biopsy diagnosis in pulmonary nodules of 15 mm or less maximum diameter. The overall sensitivity was 93% (40 of 43 lesions); specificity, 100% (21 of 21 lesions); and accuracy, 95% (61 of 64 lesions). Their diagnostic accuracy was comparable with published results in larger lesions (5). They mentioned several reasons for this good result, which included operator experience, perseverance, and repeat performance of biopsy. When they initially obtained a negative biopsy result, they performed repeat biopsy in some patients on the same day and performed repeat biopsy in 10 patients (one patient underwent two repeat biopsies) on a subsequent day. They considered additional passes performed on the same day to be part of the same procedure; thus, it is difficult to compare their results with ours. The other reported sensitivity for the detection of cancer with transthoracic needle biopsy in nodules smaller than 20 mm in diameter is 68%–96% (4,5,11–15). Our result for CT-guided needle biopsy without use of the respiratory gating device is likely to be worse than those previously reported. This is probably because we adopted a strict nodular size criterion—a maximum of less than 15 mm.

CT fluoroscopy-guided biopsy also is performed in patients with small pulmonary nodules to overcome variations in patient breathing by using real-time capability (16,17). During early experience with CT fluoroscopy, biopsy of small (<15 mm) pulmonary nodules with CT fluoroscopy was successful in 82% of 20 cases (18). This result is similar to success rates published previously for conventional CT guidance. Although CT fluoroscopy is a useful targeting technique, it is, to our knowledge, available in only a small number of centers. Furthermore, radiation exposure to the operator may result even if needle holders are used to keep the operator’s hands out of the primary beam (19).

Our study had several limitations. Many factors, including biopsy technique used, comprehensiveness of sampling, number of passes, and availability of histologic evaluation, were not taken into consideration. Moreover, the improvement in diagnostic yield with our technique was based on comparison with historical data. Although, from a statistical point of view, the comparison ideally should have been made with the standard technique in the same group of patients, we did not believe that this could be ethically justified. The next best thing would have been to have a separate group of patients concurrently undergo CT without use of the gating device. If the time frame and personnel performing biopsy had been the same, there would have been less bias. There apparently was a big difference in sensitivity between the two groups, but it was not significant. However, the most important point in the evaluation of this scheme is the comparison of accuracy in each group. Therefore, the value of our present study is warranted, in our opinion.

In summary, we developed a respiratory gating technique that allows CT-guided needle biopsy of small pulmonary nodules. The technique is useful in patients who are unable to hold their breath at a given respiratory level.

	ACKNOWLEDGMENTS

 
We thank Nestor L. Müller, MD, PhD, for his assistance with manuscript editing, and Masayuki Sogabe of GE Yokogawa Medical Systems for his technical contribution.

	FOOTNOTES

 
Author contributions: Guarantors of integrity of entire study, N.T., N.M.; study concepts, N.T., T.J.; study design, N.T., N.M.; definition of intellectual content, T.J.; literature research, N.T., O.H.; clinical studies, N.T., N.M., T.K., M.M.; data acquisition, N.M., M.M.; data analysis, N.T., S.H.; statistical analysis, N.T., T.J.; manuscript preparation, N.T., T.J.; manuscript editing, N.T.; manuscript review, all authors.

	REFERENCES

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