1. Novel Surgical Approach for Localization and Excisional Biopsy of Small or Ill-defined Pulmonary Lesions Thomas M. Daniel, M.D. Section of General Thoracic Surgery University of Virginia School of Medicine Charlottesville, Virginia

2. Frequency and Mortality of the Most Commonly Diagnosed Cancers 150200 100500 Lung Number (x10 3 ) Colon Breast Prostate Deaths New cases Cure Rate 50% 12% 75% 80% 171,000 158,900 94,700 47,500 176,300 43,700 179,300 37,000 1999 Cancer Facts and Figures, American Cancer Society

3. Characteristics of 95 nodules seen in 184 patients entered in UVA lung cancer screening program Calcified 5% < 3 mm 36% 3 to 6 mm 43% >6 and <10 mm 6% = to or >10 mm 10% 52% had nodules. 85% were less than 10mm!

4. Review of Intraoperative Localization Techniques for Excisional Biopsy of Small Lung Nodules Needle localization Ultrasound localization Fluoroscopic localization using solid and liquid radio-opaque substances Radiotracer localization

5. Needle Localization Experiments attempt to mimic breast biopsy experience UVA animal laboratory experiment using four different hook needle designs Goal: Test ability of hooks to stay in place near small lung lesions to guide thoracoscopic biopsy

6. 4 hook needle designs Depth gauge

7. Results of Needle Localization Experiments ALL needles failed to remain in place with minimal standardized resistance Summary: - needle localization in lung tissue is ineffective

8. Solid Marker Localization Experiments Neurosurgical coil with ultrasound localization under saline – UVA ex vivo sample coil

9. Solid Marker Localization Experiments CT fluoroscopy guided injection of cyanoacrylate via 22 gauge needle- Yoshida-Japanese JTCVS 1999; 47: 210-3 Summary- Hardness of both localization materials with coil and cyanoacrylate made subsequent frozen pathologic evaluation difficult. Both techniques exposed OR team and patient to fluoroscopy.

10. Liquid Radio-Opaque Nodule Localization Techniques Okumura-ATS 2001;71:439-42 CT-guided bronchoscopic barium sulfate marker placed in or near nodule Subsequent fluoroscopy-assisted thoracoscopic excisional biopsy ( FATS-BM ) 20 patients- all nodules successfully biopsied. Average distance from outer margin of lesion to nearest pleural margin was 6.5mm ( 0-18 mm)

11. Lung noduleCT fluoroscopyBarium placed near nodule

12. E= thoracoscopic stapling device F= endograsper with nodule Fluoroscopic view

13. Liquid Radio-Opaque Techniques- continued Nomori-ATS 2002;74:170-3 Percutaneously placed Lipiodol using CT guidance- 21 gauge needle- aspirate first! Simultaneous use of colored collagen for pleural localization Fluoroscopically-assisted thoracoscopic biopsy 66 patients- Average distance from nodule margin to pleura was 19mm ( 8-30mm). Average nodule size 7mm.

14. Lung nodule Percutaneously placed Lipiodal

15. Liquid radio-opaque techniques Limitations preoperative bronchoscopic localization takes time, high level of skill and exposes bronchoscopist and patient to radiation from fluoroscopy Both techniques require intraoperative fluoroscopy which is of limited use with the patient in the lateral decubitus position and exposes patient and staff to radiation from fluoroscopy

16. Radiotracer Nodule Localization Study Chella-European JCTS 2000;18:17-21 Percutaneous injection of Technetium labeled human serum albumin microspheres using CT guidance and 22 gauge needle Thoracoscopic biopsy 2 hours later using gamma ray detector- 11mm diameter 39 patients- all nodules successfully located. Mean nodule size 8.3mm. Mean distance from pleura 13mm ( 6-30mm)

17. Digital display of gamma ray emissions Videoscopic view of radiation probe zero degree radioprobe

18. University of Virginia nodule localization study First step-laboratory testing of technique using small animal model and three readily-available Technetium radiotracers ( MAA- used in lung perfusion scans, Sulfur colloid- used in breast cancer sentinel node location, and unbound pertechnetate as control) Second step- clinical application with IRB approval

19. University of Virginia nodule localization experience November 2002-August 2004 29 patients age 48-85 19 males 10 females 27 had >20PY smoking history average distance from pleural surface to lesion on CT scan-13.3 mm (1-50) average nodule size- 11mm (1-22)

20. Results 2 pneumothoraces during needle placement. No surgical complications 2 lesions had disappeared and were not present on day-of-surgery CT scans 96% of remaining 27 lesions successfully localized and biopsied 13 of 27 lesions were malignant 10 primary lung cancers- 9 Stage IA, I Stage IB 3 solitary metastatic lesions in smokers with previous history of malignancy (colon, 2 melanoma)

21. Tc-99m MAA lung nodule localization - Requires no special technology. - Permits predictable localization and thoracoscopic biopsy of small or ill-defined lung nodules - Remains useful for nodule localization if VATS is converted to open thoracotomy due to location or pleurodesis - BUT endoscopic stapling technique for excision of small nodules is awkward and often results in excessive lung tissue removal

22. Laboratory experiment combining radiotracer localization technique with 1318-nm Nd:YAG laser excision eight pig lungs studied using open thoracotomy Tn 99m MAA radiotracer solution injected transpleurally up to 1 cm deep to create a “lesion” Gamma radioprobe used to guide 1318-nm Nd:YAG laser excision of radioactive “lesion” lung specimens evaluated with combined scintigram/radiogram to determine accuracy of excision

23. A B A – injection of radiotracer to create lesion B – YAG laser excision guided by radioprobe C – combined scintigram/radiograph showing complete excision of lesion Combined technology experiment for nodule localization and excision C

24. Ventilated pig lung with saline-filled biopsy site after cautery excison (left) and 1318 YAG excision (right)

25. Conclusions Radiotracer localization allows accurate and predictable localization of small or ill-defined lung lesions in patients at high risk for lung cancer Current lung stapling technology limits its use 1318-nm Nd:YAG laser technology when adapted to radiotracer-guided thoracoscopic surgery may allow excisional biopsy of small pulmonary lesions without excessive tissue removal

26. Acknowledgements Department of Radiology- University of Virginia Talissa Altes, MD Patrice Rehm, MD Mark Williams, PhD Alexander Stolin, MS Bijoy Kundu, PhD Spencer Gay, MD Juan Olazagasti, MD Matthew Bassignani, MD Jonathan Ciambotti, MD Fachkrankenhaus Coswig- Germany Dr. Axel Rolle Department of Surgery- University of Virginia David Jones, MD Brendon Stiles, MD Kirk Barbieri Brian Trotta, 2 nd year UVA Medical Student