Ann Thorac Surg 2008;85:S772-S777. doi:10.1016/j.athoracsur.2007.10.105
© 2008 The Society of Thoracic Surgeons
Supplement: The Minimally Invasive Thoracic Surgery Summit
Identification of Small Lung Nodules: Technique of Radiotracer-Guided Thoracoscopic Biopsy
Eric L. Grogan, MD, MPH*,
David R. Jones, MD,
Benjamin D. Kozower, MD,
Winsor D. Simmons, RN,
Thomas M. Daniel, MD
Department of Surgery, Division of Thoracic and Cardiovascular Surgery, University of Virginia School of Medicine, Charlottesville, Virginia
* Address correspondence to Dr Grogan, Thoracic and Cardiovascular Surgery Outcomes, Heart & Vascular Center, PO Box 800679, University of Virginia Health System, Charlottesville, VA 22908-0679 (Email: elg9q{at}virginia.edu).
Presented at the Minimally Invasive Thoracic Surgery Summit, New York, NY, June 8–9, 2007.
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Abstract
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Background: This study describes a thoracoscopic technique to reliably locate and excise lung nodules that were not thought to be thoracoscopically visible or instrumentally palpable.
Methods: Initial laboratory studies succeeded in selecting a technetium 99m gamma-emitting solution, technetium 99m macro-aggregated albumin, that remained localized in lung parenchyma after percutaneous placement. Subsequently, 84 patients with solitary small nodules underwent computed tomography (CT)–guided percutaneous placement of this technetium solution in or near the nodule. Thoracoscopic localization with a radioprobe and excisional biopsy followed.
Results: In 3 patients, the previous lesion was not present on the CT scan done on the day of surgery. The 81 remaining patients underwent radiotracer placement and operation. No tracer activity was present in the lung in 4 patients, and open thoracotomy was necessary to locate the lesion. The lesion was successfully localized and excised in 77 patients (95.1%), and 71 underwent thoracoscopic excisional biopsy. Four underwent intentional thoracotomy for deep small nodules in which the tracer was used to guide the open biopsy. Two required conversion from thoracoscopy to thoracotomy because the anatomic location of the lesion prevented a thoracoscopic staple excision. Fifty percent of the lesions were benign, 39% were primary lung cancers, and additional 11% were either solitary metastatic lesions or lymphoma. No patients died, and morbidity rate was 16% (arrhythmias or pneumothoraces).
Conclusions: Radiotracer-guided thoracoscopic biopsy was 95% reliable for subsequent surgical successful localization and excision of small nodules. This technique can be expanded to localize deep lesions for open thoracotomy and be used to prevent thoracotomy in 50% of patients with benign disease.
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Introduction
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Thoracic surgeons are being asked to evaluate and manage an increasing number of patients with small lung nodules. Reasons for this include (1) finding nodules on computed tomography (CT) scans used for staging extrathoracic malignancies, (2) finding an incidental lung nodule using new technologies such as the 64-slice CT and the electron beam CT to evaluate coronary calcification, and (3) the increasing use of screening CT scans for patients at high risk for lung cancer in clinical trials and medical practice [1, 2].
Many of the small nodules found with increasing use of improved CT technologies are located in areas of the lung abutting the mediastinum, diaphragm, and apex. These nodules may also lie more than 1 cm deep to the pleura and are frequently not localizable with the routine thoracoscopic techniques. In the past, when dealing with larger nodules, thoracic surgeons have believed that they could always obtain a tissue diagnosis thoracoscopically by visualization, instrumental palpation, or digital palpation, followed by excision. Small nodules in these difficult locations can be challenging to locate without a thoracotomy, however, thereby subjecting patients who ultimately are shown to have a benign diagnosis to unnecessary morbidity. Surgeons may also be more reluctant to be aggressive in obtaining an excisional biopsy if they believe a thoracotomy would be necessary.
The failure of routine thoracoscopy to predictably localize and excise such small nodules has led to many innovative techniques to achieve this goal. These include wire hook and coil markers [3], radiopaque markers using intraoperative fluoroscopy [4, 5], ultrasound guidance [6], and most recently, navigational bronchoscopy [7]. At the University of Virginia School of Medicine, we modified a technique first described by Chella and colleagues [8] that used CT-guided percutaneous placement of a technetium (Tc) radiotracer in or near the small lung nodule to guide subsequent thoracoscopic biopsy. We used Tc 99m macro-aggregated albumin (MAA) that stayed localized in lung parenchyma for up to 18 hours. We designed a long narrow radioprobe (RMD Instruments, LLC, 44 Hunt St, Watertown, MA) with an angled 30° tip to help with the thoracoscopic localization and excision of the nodule. This report describes the results, lessons learned, and expanded applications of the radiotracer guided thoracoscopic nodule excision in 84 patients.
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Materials and Methods
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Laboratory Tests for Radiotracer Stability in Lung Tissue
Three Tc 99m radiotracer solutions were tested in a Sprague-Dawley rat model to determine their relative stability over time after percutaneous placement in the animal’s lung. Two readily available solutions were chosen. One was Tc 99m MAA, which is routinely used in hospitals as the intravenous injectate for lung perfusion scans. The particle size of Tc 99m MAA is approximately 10 to 50 µm. This was larger than the Tc 99m human serum albumin particle (approximately 10 nm) used by Chella and colleagues [8]. We hoped that it would therefore stay in place longer and allow more time and flexibility in getting to the operating room than Chella’s group experienced. The second solution was Tc 99m sulfur colloid, which is routinely used in melanoma and breast cancer surgery to determine sentinel lymph nodes and has a particle size of approximately 100 to 200 nm [9p1762]. The third substance was unbound pertechnetate as a control. A dual-modality 5-mm animal scanner consisting of a digital radiograph integrated with a gamma camera allowed the two images to be superimposed. The technique and the results of this study have been described in previous publications [9–11]. On the basis of these studies, Tc 99m MAA solution was selected owing to its ability to remain confined to a small area of the lung up to 4 hours after percutaneous placement.
Patients
Between November 2002 and August 2006, 84 patients (Fig 1) were selected in the clinic for CT-guided radiotracer placement in the vicinity of their small lung nodule, followed by attempted thoracoscopic localization and excisional biopsy. All patients had been referred to our thoracic surgical service for the evaluation and management of a solitary lung nodule. Patient selection for this procedure by the thoracic surgeons was by the size of the nodule, its ground-glass or solid characteristics, its depth from the pleural surface, and the region of the lung that it lay in. The role of clinical judgment in this decision was difficult to quantify. For example, small and larger ground-glass lesions might not be expected to be apparent, thoracoscopically, as a mass when embedded in an atelectatic lung. Similarly, a small subpleural lesion located in the lateral lung adjacent to the chest wall might be easily palpable digitally or with an endoscopic instrument. This same lesion located in the lung adjacent to the mediastinum would not be palpable and was selected for tracer localization. This procedure has a built-in mechanism to guard against unnecessary operations for those patients whose small nodules disappeared between their office visit and their scheduled procedure in that a repeat CT was always obtained immediately before the operation as part of the localization process. Studies were approved by the University of Virginia Institutional Review Board for Health Sciences Research #12429, and individual consent was waived.
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Fig 1. Flow diagram of clinical results from 84 patients selected for radiotracer-guided biopsy. (CT = computed tomography.)
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Technique
On the morning of the operation, under conscious sedation, all patients underwent a limited CT scan without contrast to confirm the nodule’s location. If the nodule was not present, the tracer placement and subsequent procedure were cancelled. The operating surgeon and CT radiologist mutually decided on the best approach angle for the radiotracer placement with the goal being to place the tracer just deep to the lesion so the subsequent radiotracer-guided wedge biopsy would incorporate the proximal lesion in the wedge of lung tissue removed.
A 20-guage coaxial needle was positioned in the chest wall along the intended track of the radiotracer placement needle and positioned just proximal to the pleural cavity. A 22-gauge spinal needle was then advanced through this needle into or just deep to the lung nodule under CT fluoroscopy (Fig 2). Care was taken to choose an angle of position to avoid injecting the radiotracer near the pleural surface of a major fissure. Once properly positioned, 0.1 mL of Tc 99m MAA (approximately 0.3 mCi) was injected. An immediate postprocedure nuclear medicine scintigram was obtained to confirm the intraparenchymal location of the radiotracer. The patient then recovered from conscious sedation, reported to the surgical admission suite, and was subsequently taken to the operating room.
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Fig 2. Computed tomography (CT)–guided percutaneous placement of technetium 99m macro-aggregated albumin radiotracer near a lung nodule. (A) The arrow on this CT scan points to an 8-mm nodule. (B) The radiologist uses CT fluoroscopy to place the radiotracer near the nodule. (C) The appearance of nodule on prone CT scan, with the long arrow showing track of the needle containing the tracer solution.
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General anesthesia with single-lung ventilation was induced. The patient was placed in the lateral decubitus position and adequately prepared and draped. As we gained experience, we learned to first locate the area of maximum signal on the external chest wall by using the sterile gamma radioprobe. This helped to plan the subsequent thoracoscopic port sites. Three incisions were then made: one for a 10-mm 30° thoracoscope, one for a 5-mm endoscopic grasper, and a 10-mm site for alternating use of the gamma probe and an endostapler (Fig 3). In patients whose lung did not deflate well, carbon dioxide insufflation was used.
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Fig 3. Radiotracer-guided intraoperative localization. The anesthetized patient is in the lateral decubitus position. The arrow points to the port site used for alternating insertion of the endostapler and the radioprobe.
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After localization with the radioprobe, the area of the lung parenchyma with the maximum radioactive signal was grasped and elevated with 5-mm endoscopic grasper. The angled radioprobe was rotated to confirm the lesion’s location from multiple angles using maximal signal intensity as a guide. This helped to determine the depth of the lesion in relation to the grasper. During the stapling process, the radioprobe was reintroduced as often as necessary to be certain that the lung tissue that was excised contained the maximum radio signal. The lesion was wedged out with the endostapler, and the specimen removed in an endobag.
Once the lesion was removed, the radioprobe was used to confirm the absence of strong signal in the remaining lung and also to determine the site of maximum activity in the specimen. This area on the specimen was marked with a suture for immediate frozen-section pathologic examination. Patients found to have primary lung cancers underwent immediate open thoracotomy or video-assisted thoracotomy with lobectomy or segmentectomy, followed by complete nodal staging.
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Results
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Results of Radiotracer-Guided Procedure
The clinical criteria described in "Methods" were used to select 84 patients referred for the evaluation of small solitary lung nodules for radiotracer-guided thoracoscopic excisional biopsy (Fig 1). In 3 patients, the nodule was no longer present in the CT that was done before the radiotracer placement on the surgery. The remaining 81 patients underwent CT-guided placement of Tc 99m MAA in or just deep to their nodule. In 4 patients the tracer activity was discovered at operation to lie either in the pleural space or in the chest wall, and they underwent open thoracotomy and biopsy. This experience early in our series led to the adoption of routine post-CT placement scintigrams to confirm parenchymal placement of the radiotracer. When the tracer was present in the lung, as it was in 77 patients, we experienced 100% success in localizing and excising the small nodule.
Thoracoscopic excisional biopsies were done in 71 patients (92%), and 4 (5%) underwent intentional thoracotomy for deep nodules that the surgeon believed were not removable by the thoracoscopic stapling technique. These lesions were not palpable at open thoracotomy and required radioprobe guidance for localization and successful excisional biopsy. Two patients (3%) required conversion to open thoracotomy and biopsy after thoracoscopic assessment of the nodule’s actual location by the operating surgeon judged the nodule was too deep for thoracoscopic wedge excision. All patients found to have primary lung cancers underwent an immediate lobectomy and nodal staging or, if severe emphysema was present, underwent a segmentectomy with nodal staging.
The average length of stay for patients found to have benign lesions, metastatic lesions, or primary pulmonary lymphoma, all of whom had wedge biopsies, was 2.2 days. The average length of stay for patients undergoing lobectomy or segmentectomy was 5 days.
Of the 77 patients (42 men, 35 women) going on to operation after successful lung tracer placement, 83% had a history of current or former smoking. The average age was 61.7 years (range, 33 to 80 years).
Morbidity and Mortality
Minor complications occurred in 16% (12 of 77) of the patients who underwent tracer injection and excisional biopsy. Placement of a pigtail catheter in the radiology suite was required in 8 patients to treat pneumothoraces that developed during CT-guided tracer placement. All patients were taken to the operating room and had successful localization procedures. Intraoperative or postoperative atrial arrhythmias developed in 3 patients, and 1 patient had a prolonged air leak (>6 days) after undergoing a lobectomy for a primary lung cancer. There were no deaths in our series.
Characteristics of Nodules
The mean size of all the 77 nodules that were localized and excised using the radiotracer-guided technique was 9.8 mm (range, 3 to 25 mm). The average distance from the outer edge of the nodule to the nearest pleural surface (apical, diaphragmatic, mediastinal and chest wall) was 11.7 mm (range, 0 mm [subpleural] to 50 mm).
Thirty of the 77 nodules (39%) were primary lung cancers (Fig 4), consisting of 18 adenocarcinomas, nine squamous cell carcinomas, two large cell carcinomas, and one small cell carcinoma. Of these 30 nodules, 28 were stage IA and one 9-mm squamous cancer was stage IIA secondary to an intralobar nodal metastasis. One 6-mm squamous cancer was found to have a 4-mm focus of the same cell type present in the lobe removed at operation, making the pathologic stage IIIB. Eight of the 77 nodules (10%) were solitary metastases from a current or previous known extrathoracic malignancy. One patient had a primary pulmonary lymphoma. Thus, 39 patients (50.7%) had malignant lesions, and the remaining 38 patients (49.3%) had benign lesions.
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Fig 4. Pathologic results were benign in 50% of study patients (green); lung cancer in 39% (blue); metastatic cancer in 10% (light gray); and lymphoma in 1% (dark gray).
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Additional Applications and Pitfalls of Technique
As stated in "Methods," we obtained scintigraphy immediately after tracer placement. We began this after spillage of the radiotracer into the pleural space occurred in 4 patients. Because of this, lesion was not localized and thoracotomy was required. If posttracer placement scintigraphy demonstrated that the tracer had been inadvertently placed in the chest wall or the free pleural space, a second CT-guided radiotracer injection was performed. When pleural spillage was present, saline irrigation of the pleural space at the time of surgery cleared the thorax of the pleural radiotracer and successful radiotracer-guided excision was performed using the described technique.
One patient had a successful video-assisted thorascopic surgical (VATS) excision the morning after CT-guided radiotracer placement because of an emergency that postponed the planned afternoon case. Experience also taught us that when scheduling difficulties prevented us from being able to perform the operative procedure in the afternoon, we increased the dose to 0.3 to 0.4 mL of Tc 99m MAA (approximately 0.9 to 1.2 mCi). This allowed us to have radiology place the radiotracer late in the afternoon, and then we performed the operation as the first case the next morning. If no pneumothorax occurred requiring a pigtail catheter placement, the patient was allowed to return home and report for surgery the following morning. If a pigtail was necessary, the patient was admitted to the hospital overnight.
As our experience increased with the VATS radiotracer technique, we expanded this to deep lesions for localization for intentional thoracotomy. Four patients had small indeterminate lesions that were deep within the lobe, and VATS excision was felt to be impossible. These lesions were either small or had a ground-glass appearance, and manual palpation during thoracotomy would have been challenging, potentially requiring a lobectomy for a possible benign lesion. Radiotracer was placed in these patients and they underwent planned thoracotomy with radiotracer-guided localization and wedge excision.
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Comment
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The evaluation and management of small lung nodules is becoming of increasing importance in the practice of clinical medicine. We have described a novel technique with minimal morbidity that aids in the excision and diagnosis of these small nodules. This technique is a useful tool for thoracic surgeons as their efforts increase to improve the low cure rate of lung cancer by making earlier diagnoses. This technique is also useful as an adjunct in the treatment of extrathoracic malignancies where accurate staging determines the therapy that will be most effective.
The results of our study add to the growing number of options for the evaluation and management of small lung nodules. We experienced a 95.1% success rate in making a diagnosis of small lung nodules not thought to be accessible by routine thoracoscopic or fine needle aspiration techniques. When the radiotracer was successfully placed in the lung parenchyma, as it was in 95.1% of the patients, we experienced a 100% success rate in localizing and removing the entire nodule for definitive pathologic study and margin assessment.
Compared with other techniques for small nodule localization for biopsy we see the following advantages with this technique:
- 1 all the components—Tc radiotracer, CT technology, gamma probes, and thoracoscopic equipment—are readily available at most hospitals;
- 2 the Tc 99m MAA marker has remained stable in the lung for up to 18 hours, permitting flexibility in scheduling operations;
- 3 there is no known hazard to the patient or the hospital personnel from the lose dose of radioactivity required by the technique;
- 4 the technique can mark nodules located in any region of the lung and the nodule location can be continually reassessed during the operation using the radioprobe to confirm an accurate excisional biopsy;
- 5 the localization technique does not interfere with immediate pathologic study, permitting frozen analysis of the specimen and assessment of the margins; and
- 6 minimal morbidity and mortality are associated with the procedure.
In addition, this technique can be successfully used for very small nodules (<5 mm) and larger nodules that are deep in the parenchyma that would be difficult to thoracoscopically excise. It is also useful for lesions with ground-glass appearance, which can be difficult to palpate even in open procedures.
There are two major disadvantages:
- 1 the technique requires an investment of time for communication to occur between the radiologist and the thoracic surgeon on the day of surgery to discuss the optimum approach angle of the tracer placement needle to achieve the desired target site for tracer delivery, and
- 2 the operation must be scheduled to coincide with the completion of the CT-guided injection and follow-up scintigram in the radiology suite.
The treatment algorithm for lung nodule management is now changing rapidly with the introduction of new technology and proteomic knowledge. The ability to predict individual tumor behavior according to gene arrays of tumor tissue is predicated on obtaining adequate tissue sampling. Treatment options other than surgical resection, such as radiofrequency ablation and stereotactic radiosurgery, are also being evaluated. The use of endoscopic bronchial ultrasound imaging to biopsy mediastinal and lobar lymph nodes and the use of the navigational bronchoscope to obtain a tissue diagnosis of small lung nodules without the need for routine hospitalization will undoubtedly change the algorithm for the management of small lung nodules.
The availability and reliability of the radiotracer-guided technique in diagnosing small lung nodules has had a significant influence on our treatment options when making clinical decisions and has given us an additional diagnostic tool. The technique can be used for more than one nodule, but for patients with multiple nodules and metastatic disease, we have preferred open thoracotomy to allow manual palpation of the lung. With these current techniques, our benign diagnosis rate is 49.3%. This has not decreased with our experience and will likely remain high until new imaging techniques that characterize nodules better are clinically available. Most patients and clinicians, however, are willing to accept the risks of thoracoscopy if 50% of the excised lesions are malignant.
In a rapidly changing, technology-driven environment, it is important that thoracic surgeons continue to develop, study, and implement new techniques used to diagnose and treat lung nodules. The thoracic surgeon is often the specialist who sees the patient first, knows the three-dimensional anatomy of the thorax, and can therefore make judgments about nodule accessibility for excisional biopsy using the most effective technique needed for diagnosis and treatment. In addition, thoracic surgeons are experienced in managing the complications such as tension pneumothorax, hemothorax, and massive hemoptysis, and they know the clinical behavior of lung cancer. Used by knowledgeable and thoughtful clinicians, proven diagnostic and therapeutic innovations will ultimately benefit the patient with a lung cancer or a metastatic lesion presenting as a small lung nodule.
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Acknowledgments
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This research was supported by the Commonwealth Fund for Cancer Research support to the University of Virginia Cancer Center.
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References
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Abstract
Introduction
