Accepted Manuscript. Radiotracer localization: Finding a nodule in the haystack. Jules Lin, MD

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Accepted Manuscript Radiotracer localization: Finding a nodule in the haystack Jules Lin, MD PII: S0022-5223(18)32260-8 DOI: 10.1016/j.jtcvs.2018.08.018 Reference: YMTC 13340 To appear in: The Journal of Thoracic and Cardiovascular Surgery Received Date: 10 August 2018 Accepted Date: 14 August 2018 Please cite this article as: Lin J, Radiotracer localization: Finding a nodule in the haystack, The Journal of Thoracic and Cardiovascular Surgery (2018), doi: 10.1016/j.jtcvs.2018.08.018. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 Radiotracer localization: Finding a nodule in the haystack Jules Lin, MD 1 1 University of Michigan Medical Center, Department of Surgery, Section of Thoracic Surgery, Ann Arbor, Michigan Conflicts of interest: There are no potential conflicts of interest. Word count: 497 Central Message: Radiotracer localization can be a useful tool in identifying small, part-solid, or deeper nodules which are becoming increasingly common with the growth of lung cancer screening. Please address correspondence to: Jules Lin, MD Associate Professor, Section of Thoracic Surgery 1500 E. Medical Center Drive, 2120TC/5344 Ann Arbor, MI 48109-5344 22 23 (734)-763-0470 E-mail: juleslin@umich.edu

1 2 In this issue, Starnes and colleagues describe a retrospective series of 77 patients who underwent radiotracer localization of pulmonary nodules. 1 Several previous papers have been 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 published on this topic including one with 211 patients and one randomized study. 2 4 Radiotracer localization can be useful in identifying small, part-solid, or deeper nodules which can be challenging to identify thoracoscopically like the proverbial needle in a haystack and are becoming increasingly common with the growth of lung cancer screening. The indications for localization (size, depth, solid component) were not clearly defined, and patients were selected when a thoracic surgeon felt the nodule would be difficult to identify thoracoscopically. Other studies selected nodules with subsolid morphology, < 1 cm in size, or deeper than 1 cm from the pleura. 2,3 Nodules in the current study were only a median 5 mm in depth compared to studies by Galetta et al. (12 mm) and Gonfiotti et al. (2.5 cm). There were also a variety of nodules in the current study with 56% groundglass/subsolid and 44% solid while Galetta et al. only included 17.1% solid nodules. Was localization necessary for these nodules and could some have been approached with needle biopsy? Unfortunately, data was not available on whether these nodules were palpable. Gonfiotti et al. randomized patients to wire versus radiotracer localization and found that nodules were palpable in 28% and 24% of patients. The pneumothorax rate was higher in the current study (47%) with 9% of patients requiring a chest tube. Ambrogi et al., Galetta et al, and Gonfiotti et al. found a pneumothorax rate of 10.4%, 29.4%, and 4% requiring a chest tube in 0%, 0%, and 0.8%. One potential explanation is that a 19G coaxial needle was used in the current study while Galetta, et al. used a 25G needle and Ambrogi et al. and Gonfiotti et al. used a 22G needle. 2 4 While the authors 22 flushed the needle to improve radiotracer deposition, it was unclear why they used 1% lidocaine

23 24 and not saline. Other authors have injected nonionic contrast to visualize the relationship to the nodule and better guide localization. 25 26 27 28 29 30 31 32 33 34 35 36 It is unclear if radiotracer localization decreased the need for thoracotomy or anatomical resection for tissue diagnosis with no comparison to a control group although the success rate of 95% was similar to previous studies (96-99%). 2 4 In all four failures, nodules were < 6 mm in depth with radiotracer coming out of the hole in the pleura. Ambrogi et al. described 2 cases where radiotracer escaped into the pleural space which was irrigated with saline to reduce background activity allowing the nodule to be identified. 3 Placement of radiotracer, dye, wires, coils, or radiopaque markers each have their advantages and disadvantages, but the best approach may depend on local expertise. Radiotracer localization is feasible with a high rate of success. The technology is available in most hospitals due to widespread use of sentinel lymph node biopsies and may be a useful tool for finding a nodule in the haystack.

37 38 REFERENCES 1. Starnes SL, Wolujewicz M, Guitron J, Williams V, Scheler J, Ristagno R. Radiotracer 39 40 41 42 43 44 45 46 47 48 49 50 localization of nonpalpable pulmonary nodules: A single-center experience. J Thorac Cardiovasc Surg. April 2018. doi:10.1016/j.jtcvs.2018.03.152 2. Galetta D, Bellomi M, Grana C, Spaggiari L. Radio-Guided Localization and Resection of Small or Ill-Defined Pulmonary Lesions. Ann Thorac Surg. 2015;100(4):1175-1180. doi:10.1016/j.athoracsur.2015.04.092 3. Ambrogi MC, Melfi F, Zirafa C, et al. Radio-guided thoracoscopic surgery (RGTS) of small pulmonary nodules. Surg Endosc. 2012;26(4):914-919. doi:10.1007/s00464-011-1967-8 4. Gonfiotti A, Davini F, Vaggelli L, et al. Thoracoscopic localization techniques for patients with solitary pulmonary nodule: hookwire versus radio-guided surgery. Eur J Cardio-Thorac Surg Off J Eur Assoc Cardio-Thorac Surg. 2007;32(6):843-847. doi:10.1016/j.ejcts.2007.09.002