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Localization Techniques for Small Lung Nodules

  • Daniel G. Cuadrado
    Affiliations
    Department of Cardiac Surgery, Tennessee Valley Healthcare System, Nashville Campus, Vanderbilt University Medical Center, South Nashville, TN
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  • Eric L. Grogan
    Correspondence
    Address reprint requests to Eric L. Grogan, MD, MPH, FACS, Department of Thoracic Surgery, Tennessee Valley Healthcare System, Nashville Campus, Vanderbilt University Medical Center, 609 Oxford House, 1313 21st Ave, South Nashville, TN 37232.
    Affiliations
    Department of Thoracic Surgery, Tennessee Valley Healthcare System, Nashville Campus, Vanderbilt University Medical Center, South Nashville, TN.
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      Introduction

      During the time of plain chest radiographs, it was felt that all noncalcified pulmonary nodules in smokers older than 50 years should be managed as potentially malignant lesions unless they demonstrated radiographic stability over a 2-year period.
      • Tan B.B.
      • Flaherty K.R.
      • Kazerooni E.A.
      • et al.
      American College of Chest Physicians. The solitary pulmonary nodule..
      A better understanding of the natural history of small (<7 mm) nodules has been garnered with the advent and expanded use of screening computerized tomography (CT).
      • Swensen S.
      • Jett J.
      • Hartman T.
      • et al.
      CT screening for lung cancer: Five-year prospective experience.
      Current evidence suggests that less than 1% of nodules smaller than 7 mm exhibit malignant behavior when followed over 2 years.
      • Swensen S.
      • Jett J.
      • Hartman T.
      • et al.
      CT screening for lung cancer: Five-year prospective experience.
      • Benjamin M.S.
      • Drucker E.A.
      • McLoud T.
      • et al.
      Small pulmonary nodules: Detection at chest CT and outcome.
      The recently published American College of Chest Physicians recommendations suggest that a surgical biopsy should be obtained for highly suspicious nodules ≥8 mm with a greater than 65% chance of malignancy.
      • Gould M.K.
      • Donington J.
      • Lynch W.R.
      • et al.
      Evaluation of individuals with pulmonary nodules: When is it lung cancer? Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines.
      Small pulmonary nodules will continue to present a challenge to thoracic surgeons when a tissue diagnosis is required.
      • Suzuki K.
      • Nagai K.
      • Yoshida J.
      • et al.
      Video-assisted thoracoscopic surgery for small indeterminate pulmonary nodules: Indications for preoperative marking.
      As lung cancer screening programs continue to evolve, more patients will present to surgeons with small nodules to establish a diagnosis. Greater than 50% of smokers older than 50 years will have a pulmonary nodule identified by screening CT scan,
      • Swensen S.J.
      CT screening for lung cancer.
      but 85% of these nodules will be too small to investigate with positron emission tomography or to biopsy either percutaneously or endoluminally with conventional bronchoscopy.
      • Nomori H.
      • Watanabe K.
      • Ohtsuka T.
      • et al.
      Evaluation of F-18 fluorodexoyglucose (FDG) PET scanning for pulmonary nodules less than 3 cm in diameter, with special reference to the CT images.
      • Ng Y.L.
      • Patsios D.
      • Roberts H.
      • et al.
      CT-guided percutaneous fine-needle aspiration biopsy of pulmonary nodules measuring 10 mm or less.
      • Schreiber G.
      • McCrory D.C.
      Performance characteristics of different modalities for diagnosis of suspected lung cancer: Summary of published evidence.
      Yet, with that in mind, early intervention with resection of malignant lesions presents these patients with the best opportunity for cure.
      Therefore, it is incumbent on thoracic surgeons to have a solid understanding of the techniques available for the minimally invasive localization of small pulmonary nodules to both diagnose and treat these patients. Often this requires a multidisciplinary approach and the coordination of various hospital resources. Although most procedures may be performed using video-assisted thoracic surgical (VATS) technique, thoracotomy remains the gold standard should all other localization methods fail.
      VATS is performed in the operating room, under general anesthesia with a double-lumen tube. Based on the patient and surgeon preference, a thoracic epidural may be placed before entering the operating theater for postoperative analgesia. The patient is positioned in the lateral decubitus position with the table flexed to maximize intrathoracic exposure. The standard precautions are taken regarding positioning to prevent impingement of the peripheral nerves. As a routine, the preoperative images should be displayed in view of the operating surgeon.
      Once the thoracic cavity has been entered and adequate pulmonary isolation is ensured, the nodule may be identified by visualization and confirmed by direct palpation. The remainder of the chest is explored and pulmonary parenchyma examined. Resection of the nodule is typically performed using endoscopic linear staplers, and the specimen is removed in an endoscopic specimen bag to prevent port-site contamination. The specimen is then sent for frozen section analysis by pathology. In the case of a benign diagnosis, a portion of the specimen is sent for microbiology, and a chest tube is placed before re-expanding the lung and closing the wounds. Malignant or indeterminate diagnosis mandate proceeding to an anatomical resection, and it is for this reason that all patients should be screened for candidacy for such resection. It is reasonable and safe to proceed via VATS with these anatomical resections.
      For those cases that the surgeon suspects a nodule may be difficult to identify intraoperatively, preoperative localization strategies may be employed. These can be broadly differentiated into bronchoscopic, radiographic, and intraoperative. Conventional bronchoscopy is practical for endobronchial and central lesions. However, for lesions less than 2 cm, the diagnostic yield for central and peripheral lesions is 31% and 14%, respectively.
      • Baaklini W.A.
      • Reinoso M.A.
      • Gorin A.B.
      • et al.
      Diagnostic yield of fiberoptic bronchoscopy in evaluating solitary pulmonary nodules.
      Navigational bronchoscopy marries radiographic images with real-time bronchscopic technology to reach lesions in proximity to the airways.
      • Schwarz Y.
      • Greif J.
      • Becker H.
      • et al.
      Real-time electromagnetic navigational bronchoscopy to peripheral lung lesions using overlaid CT images: The first human study.
      Utilizing this modality, obtaining a diagnosis is possible in upward of 80% of procedures for peripheral lesions.
      • Gildea T.R.
      • Mazzone P.J.
      • Karnak D.
      • et al.
      Electromagnetic navigational diagnostic bronchoscopy. A prospective study.
      An endobronchial fiducial or methylene blue or both can be placed as a preoperative guide to resection.
      • Linden P.A.
      Use of navigational bronchoscopy for biopsy and endobronchial fiducial placement.
      • Chen W.
      • Chen L.
      • Yang S.
      • et al.
      A novel technique for localization of small pulmonary nodules.
      In the interventional radiology suite, a localization wire may be placed to serve as a visual guide to resection.
      • Mack M.J.
      • Gordon M.J.
      • Postma T.W.
      • et al.
      Percutaneous localization of pulmonary nodules for thoracoscopic lung resection.
      Utilizing CT guidance, methylene blue can be injected percutaneously to aid in the identification of the nodule.
      • Lenglinger F.X.
      • Schwarz C.D.
      • Artmann W.
      Localization of pulmonary nodules before thoracoscopic surgery: Value of percutaneous staining with methylene blue.
      Furthermore, CT-guided injection of a radiotracer can be performed preoperatively followed by intraoperative localization with a gamma probe.
      • Grogan E.L.
      • Jones D.R.
      • Kozower B.D.
      • et al.
      Identification of small lung nodules: Technique of radiotracer guided thoracoscopic biopsy.
      Intraoperative localization typically relies on visual identification and digital palpation. Intraoperative ultrasound can be performed as an adjunct to aid in the localization of small nodules.
      • Santambrogio R.
      • Montorsi M.
      • Bianchi P.
      • et al.
      Intraoperative ultrasound during thoracoscopic procedures for solitary pulmonary nodules.
      For those cases in which the nodule cannot be clearly delineated by other means, conversion to thoracotomy remains the standard procedure. The following is a discussion of these various techniques (Figure 1, Figure 2, Figure 3, Figure 4, Figure 5, Figure 6, Figure 7, Figure 8, Figure 9, Figure 10, Figure 11, Figure 12, Figure 12, Figure 13, Figure 14, Figure 15, Figure 16).
      Figure thumbnail gr1
      Figure 1The stereotypical radiographic nodule detected during an incidental CT scan in a smoker. The spiculated appearance and smoking history mandate further diagnostic testing.
      Figure thumbnail gr2
      Figure 2In the previously mentioned patient, navigational bronchoscopy is used to reach the peripheral nodule. Using the radiographic images as well as the bronchoscopic software, the proceduralist may localize and biopsy the suspected lesion.
      Figure thumbnail gr3
      Figure 3Navigational bronchopscopy allows for injection of a visual marker (in this case methylene blue) that can be identified intraoperatively and used for localization of the nodule. (Color version of figure is available online at www.optechtcs.com.)
      Figure thumbnail gr4
      Figure 4CT scan of the chest depicting a peripheral spiculated growing nodule in a 64-year-old smoker with decreased functional capacity and a DLCO 45% of predicted. The patient׳s smoking history and appearance of the nodule mandate further diagnostic evaluation. DLCO = carbon monoxide diffusing capacity.
      Figure thumbnail gr5
      Figure 5In this same patient, preoperative marking of the lesion is performed using a percutaneous, CT-guided, injection of a radiographic tracer. We use technetium-99m macroaggregated albumin (99mTcMAA) that stays localized in lung parenchyma for up to 18 hours. Once properly positioned, 0.1 mL of 99mTcMAA (approximately 0.3 mCi) is injected. This image depicts needle localization by the interventional radiologist on the morning of surgery. Accurate positioning of the needle is confirmed by CT scan.
      Figure thumbnail gr6
      Figure 6This CT scan depicts the needle localized to the nodule of interest with the patient in the prone position. As a technical matter to assist in the complete resection of the nodule, it is better for the interventional radiologist to be slightly deep to the lesion to ensure that the entire nodule is removed with removal of the localization agent.
      Figure thumbnail gr7
      Figure 7With the needle localization confirmed by CT scan, the radiographic tracer is injected into the lesion.
      Figure thumbnail gr8
      Figure 8Following injection of the tracer, a nuclear scan or SPECT/CT is performed to confirm that the tracer is localized to the lesion and to ensure that no pleural spillage has occurred. SPECT = single-photon emission CT. (Color version of figure is available online at www.optechtcs.com.)
      Figure thumbnail gr9
      Figure 9Following confirmation of a successful injection, the patient is taken to the operating room. After fiberoptic bronchoscopy, a double-lumen tube is placed, the patient is positioned, and the ipsilateral lung isolated. No additional radiation precautions are necessary for the operating room staff.
      Figure thumbnail gr10
      Figure 10The thoracic cavity is entered in the standard VATS fashion, and exploration of the thoracic cavity is performed. We use a standard 3-port approach with plans for axillary thoracotomy, should conversion to open be required. If spillage of the radiotracer occurred, this is simply irrigated and suctioned.
      Figure thumbnail gr11
      Figure 11Once the chest has been entered, digital palpation of the nodule is attempted. In this case, the nodule was not palpable. Without additional localization techniques, this would mandate conversion to thoracotomy.
      Figure thumbnail gr12a
      Figure 12(A) A gamma probe is inserted through one of the port sites. We use a long narrow radioprobe (RMD Instruments, LLC, Watertown, MA) with an angled 30° tip to help with the thoracoscopic localization and excision of the nodule. Examination of the lung is performed with the probe. The probe emits an audible signal as well as a quantitative number. This is used to localize the area of maximal tracer signal. Again, emphasizing the importance of a successful injection with minimal extrapulmonary spillage.
      Figure thumbnail gr12b
      Figure 12Continued (B) Wire localization is a different approach that may be used. As with radiotracer injection, the wire is placed preoperatively by an interventional radiologist using CT guidance. On visual inspection, the wire can be easily identified. One area of potential concern is wire migration out of the parenchyma with isolation of the lung. This image depicts the wire in correct position in the nodule in question. To minimize this problem, a pneumothorax is often induced before deployment of the wire under CT guidance.
      Figure thumbnail gr13
      Figure 13Once the nodule has been localized by using the various techniques, it is removed via wedge resection with endoscopic staplers. A generous margin around either the radiographic tracer signal or localization wire is obtained. The specimen is then removed from the thoracic cavity using an endocatch bag to avoid port-site contamination.
      Figure thumbnail gr14
      Figure 14When using the radiotracer technique, following specimen removal, the gamma probe is reintroduced into the thoracic cavity. The staple line and residual lung are examined to ensure that all traces of signal have been removed. Residual tracer signal along the staple line would mandate further resection to ensure complete removal of the nodule if the resected specimen does not contain the lesion on palpation or frozen section.
      Figure thumbnail gr15
      Figure 15Once complete resection and eradication of residual signal within the chest has been confirmed, the specimen is examined on the back table.
      Figure thumbnail gr16
      Figure 16Digital palpation and gamma probe localization confirm the position of the nodule. The specimen is opened, and a portion of the nodule is removed for culture. The remainder of the nodule is sent for pathologic frozen section examination. The patient in this case was found to have NSCLC. Given his decreased DLCO, a lingula-sparing VATS left upper lobectomy was performed. DLCO = carbon monoxide diffusing capacity; NSCLC = non–small cell lung cancer.

      Summary

      The US Preventative Task Force has recommended screening for patients who are current or former smokers with >30 pack years, aged 55-74 years, and no prior history of lung cancer.
      • Humphrey L.L.
      • Deffebach M.
      • Pappas M.
      • et al.
      Screening for lung cancer with low-dose computed tomography: A systematic review to update the U.S. preventive services task force recommendation.
      As these guidelines begin to permeate to primary care physicians, we can expect a larger number of patients to be referred for diagnostic evaluation with pulmonary nodules. Thoracic surgeons can therefore expect to see increased numbers of patients with small pulmonary nodules requiring biopsy. It is therefore incumbent on the surgeons who treat these patients to have a sound knowledge of the various techniques available for preoperative localization to minimize the unnecessary open thoracotomy. A multidisciplinary approach is required to ensure that the best treatment is matched to the patient. Although these localization techniques improve a successful VATS approach, conversion to thoracotomy for digital palpations may be necessary in rare circumstances to obtain a diagnosis.

      References

        • Tan B.B.
        • Flaherty K.R.
        • Kazerooni E.A.
        • et al.
        American College of Chest Physicians. The solitary pulmonary nodule..
        Chest. 2003; 123: 89S-96S
        • Swensen S.
        • Jett J.
        • Hartman T.
        • et al.
        CT screening for lung cancer: Five-year prospective experience.
        Radiology. 2005; 235: 259-265
        • Benjamin M.S.
        • Drucker E.A.
        • McLoud T.
        • et al.
        Small pulmonary nodules: Detection at chest CT and outcome.
        Radiology. 2003; 226: 489-493
        • Gould M.K.
        • Donington J.
        • Lynch W.R.
        • et al.
        Evaluation of individuals with pulmonary nodules: When is it lung cancer? Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines.
        Chest. 2013; 143 (e93S–120S)
        • Suzuki K.
        • Nagai K.
        • Yoshida J.
        • et al.
        Video-assisted thoracoscopic surgery for small indeterminate pulmonary nodules: Indications for preoperative marking.
        Chest. 1999; 115: 563-568
        • Swensen S.J.
        CT screening for lung cancer.
        Am J Roentgenol. 2002; 179: 833-836
        • Nomori H.
        • Watanabe K.
        • Ohtsuka T.
        • et al.
        Evaluation of F-18 fluorodexoyglucose (FDG) PET scanning for pulmonary nodules less than 3 cm in diameter, with special reference to the CT images.
        Lung Cancer. 2004; 45: 19-27
        • Ng Y.L.
        • Patsios D.
        • Roberts H.
        • et al.
        CT-guided percutaneous fine-needle aspiration biopsy of pulmonary nodules measuring 10 mm or less.
        Clin Radiol. 2008; 63: 272-277
        • Schreiber G.
        • McCrory D.C.
        Performance characteristics of different modalities for diagnosis of suspected lung cancer: Summary of published evidence.
        Chest. 2003; 123: 115S-128S
        • Baaklini W.A.
        • Reinoso M.A.
        • Gorin A.B.
        • et al.
        Diagnostic yield of fiberoptic bronchoscopy in evaluating solitary pulmonary nodules.
        Chest. 2000; 117: 1049-1054
        • Schwarz Y.
        • Greif J.
        • Becker H.
        • et al.
        Real-time electromagnetic navigational bronchoscopy to peripheral lung lesions using overlaid CT images: The first human study.
        Chest. 2006; 129: 988-994
        • Gildea T.R.
        • Mazzone P.J.
        • Karnak D.
        • et al.
        Electromagnetic navigational diagnostic bronchoscopy. A prospective study.
        Am J Respir Crit Care Med. 2006; 179: 982-989
        • Linden P.A.
        Use of navigational bronchoscopy for biopsy and endobronchial fiducial placement.
        Innovations. 2011; 6: 271-275
        • Chen W.
        • Chen L.
        • Yang S.
        • et al.
        A novel technique for localization of small pulmonary nodules.
        Chest. 2007; 131: 1526-1531
        • Mack M.J.
        • Gordon M.J.
        • Postma T.W.
        • et al.
        Percutaneous localization of pulmonary nodules for thoracoscopic lung resection.
        Ann Thorac Surg. 1992; 53: 1123-1124
        • Lenglinger F.X.
        • Schwarz C.D.
        • Artmann W.
        Localization of pulmonary nodules before thoracoscopic surgery: Value of percutaneous staining with methylene blue.
        Am J Roentgenol. 1994; 163: 297-300
        • Grogan E.L.
        • Jones D.R.
        • Kozower B.D.
        • et al.
        Identification of small lung nodules: Technique of radiotracer guided thoracoscopic biopsy.
        Ann Thorac Surg. 2008; 85: S772-S777
        • Santambrogio R.
        • Montorsi M.
        • Bianchi P.
        • et al.
        Intraoperative ultrasound during thoracoscopic procedures for solitary pulmonary nodules.
        Ann Thorac Surg. 1999; 68: 218-222
        • Humphrey L.L.
        • Deffebach M.
        • Pappas M.
        • et al.
        Screening for lung cancer with low-dose computed tomography: A systematic review to update the U.S. preventive services task force recommendation.
        Ann Intern Med. 2013; 159: 411-420