A. Kır*, İ. İskender*, A. Ko şar *, A.K. M ısırlıoğlu *, H. S önmez *, M. Demir*, A. Atasalihi*

1. A. Kır*, İ. İskender*, A. Koşar*, A.K. Mısırlıoğlu*, H. Sönmez*, M. Demir*, A. Atasalihi* Süreyyapaşa Chest Diseases and Thoracic Surgery Training and Investigation Hospital *II. Thoracic Surgery Department The Role of Mediastinoscopy on Staging of Non-small Cell Lung Cancer Patients with Negative Mediastinal Lymph Node Uptake on Positron Emission Tomography Imaging

2. In this study, the role of mediastinoscopy in the evaluation of occult N2 disease in NSCLC patients potential resectable with negative mediastinal lymph node uptake of F-18 fluorodeoxyglucose marked PET-CT is investigated.

3. Materials and Methods • September 2005 – December 2007 • Known or suspicious for NSCLC • 214 consecutive patients • Results of PET/CT and mediastinoscopy are recorded

4. Patients excluded from the study: (n=115) • Positive mediastinal lymph nodes on PET/CT • Time interval between PET and mediastinoscopy > 6 weeks • Neoadjuvant therapy • Patients with negative mediastinoscopy result underwent surgical resection and systematic lymph node sampling.

5. Complete history and physical examination • Blood analyses • Chest radiography • Spirometry • Cardiac investigation • Thorax CT • PET/CT • Cranial MRI

6. PET Imaging: • 69 patients (%70) Siemens Biograph LSO HI-REZ integrated PET/CT; two centers • Serum glucose concentration <150 mg/dl • Imaging from neck to hip • 90-150 minute after intravenous injection of FDG-18 • Fusion of PET and CT images

7. The evaluation of mediastinal lymph nodes SUVmax >2.5 was considered to be positive for metastatic disease. *Knoepp UW, Ravenel JG. CT and PET imaging in non-small cell lung cancer. Critical Reviews in Oncology/Hematology. 2006 Apr;58(1):15-30.

8. Surgical staging • Cervical mediastinoscopy • Extended cervical mediastinoscopy • Naruke classification • paratracheal (2R-2L), • tracheobronchial (4R-4L) • subcarinal (7) • Subaortic (5), paraaortic (6) • Thoracotomy

9. Results • The incidence of occult N2 diseasewas %3.1 (3 of 99) • 94 male, 5 female • Mean age: 58.5years (37-80 ) • PET scan – Mediastinoscopy: 15.9 days (2-41 ) • The diagnosis wasmade on 80 (%80.8) patients preoperatively • A total of 427 mediastinal lymph node samplings were done (4.31 stations/patient)

10. Cell types

11. Types of the Operations

12. Pathological staging Stage IIA 2 (%2)

13. Analysis of factors associated with occult N2 disease VARIABLEPATHOLOGICAL N2 PATHOLOGICAL NON-N2 P -value (N=3) (N=96) SEX MALE 3 (%100) 91 (%95) FEMALE 0 5 (%5) N/S CELL TYPES SQUAMOUS 2 (%67) 58 (%60) NON-SQUAMOUS1 (%33) 38 (%40)N/S SITE R 3 (%100) 58 (%60) L 0 38 (%40) N/S SITEandNODES (PET) R N0 2 (%67) 36 (%38) N1 1 (%33) 22 (%23) N/S L N0 0 32 (%33) N1 0 6 (%6) N/S LOCATION CENTRAL 2 (%67) 61 (%64) NON-CENTRAL 1 (%33) 35 (%36) N/S

14. VARIABLEPATHOLOGICAL N2 PATHOLOGICAL NON-N2 P-value (N=3) (N=96) LOBAR DISTRIBUTION RUL 3 (%100) 35 (%36) 0.04* RML0 4 (%4) RLL 0 19 (%20) LUL 0 26 (%27) N/S LLL 0 12 (%13) TUMOUR SIZE ≤ 3 CM 1 (%33) 29 (%30) > 3 CM 2 (%67) 67 (%70) N/S T STAGE T1/2 3 (%100) 63 (%66) T3/4 0 33 (%34) N/S ENLARGED N2 on CT NO 3 (%100) 86 (%90) YES 0 10 (%10) N/S POSITIVE N1 on PET NO 2 (%67) 68 (%71) YES 1 (%33) 28 (%29) N/S SUVmax PRIMARY ≤15 3 (%100) 52 (%54) >15 0 44 (%46) N/S Mean SUVmax: 14.5 +/- 6.8

15. Evaluation on PET negativeof 3 patients • Localization PET N2 node • 1. RUL 10R(+) 4R,(10R) • 2. RUL neg 2R,4R • 3. RUL neg 4R,7

16. Comment • Mediastinoscopy is still gold standart on the assessment of the mediastinal lymph nodes. • Sensitivity %80, spesificity %100 • %0.5 complication risk *Graeter TP, Hellwig D, Hoffmann K, Ukena D, Kirsch CM, Schafers HJ. Mediastinal lymph node staging in suspected lung cancer: comparison of positron emission tomography with F-18-fluorodeoxyglucose and mediastinoscopy. Ann Thorac Surg. 2003 Jan;75(1):231-5

17. PET/CT and Mediastinoscopy 2007 (n=106) 2008 (n=200)

18. Vincent Young at all* • 153/215 (%71.2) PET negative • 25/153 (%16) N2 positive • Right upper lobe, centrally located tumours,PET N1 (+) • ** • 99/214 (%46.3) PET negative • 3/99 (%3.1) N2 positive • Right upper lobe • *Al-Sarraf N, Aziz R, Gately K, Lucey J, Wilson L, McGovern E,Young V. Pattern and predictors of occult mediastinal lymph node involvement in non-small cell lung cancer patients with negative mediastinal uptake on positron emission tomography. Eur. J. Cardiothorac. Surg., January 2008; 33: 104 - 109.

19. ESTS guidelines for preoperative lymph node staging* • Invasive procedures can be omitted in patients • Peripheral tumours • PET negative • Invasive staging remains indicated • Central tumours, • PET hilar N1 disease, • Low FDG uptake of theprimary tumour • LN≥ 16 mm on CT scan • *De Leyn P, Lardinois D, Van Schil PE, Rami-Porta R, Passlick B, Zielinski M, Waller DA, Lerut T, Weder W. ESTS guidelines for preoperative lymph node staging for non-small cell lung cancer. Eur. J.Cardiothorac. Surg., July 2007; 32: 1 - 8.

20. Invasive mediastinal procedures are necessary for exact lymph node staging in PET positive patients • We recommend preoperative cervical mediastinoscopy in NSCLC patients on positron emission tomography with negative mediastinal lymph node uptake on right upper lobe tumours in order to rule out occult N2 disease.