Lung Cancer
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The Challenge of Mediastinal Staging

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Published Online: Jun 3rd 2011 European Oncology & Haematology, 2011;7(1):31-35 DOI:
Authors: Loris Ceron, Lucio Michieletto, Andrea Zamperlin, Laura Mancino
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Lung cancer staging is a crucial step in both correct prognosis and therapy. Mediastinal staging in particular is usually accomplished using imaging techniques such as computed tomography and 18F–glucose positron-emission tomography, minimally invasive techniques, i.e. transbronchial needle aspiration with or without ultrasound guidance (endobronchial ultrasound) and transoesophageal ultrasound-guided fine needle aspiration and surgical procedures, i.e. mediastinoscopy, thoracoscopy. Each of these techniques has its own sensitivities, specificities and predictive values that must be thoroughly considered within the staging route, with the aim of achieving the best result with the least resource consumption and the least discomfort to the patient; the correct evaluation of a negative result on the basis of its predictive value is essential as well. In this article we suggest a mathematical model that can predict the probability of nodal metastasis after a certain number of diagnostic procedures has been performed, providing an objective way of evaluating whether a patient is fit for surgery or, conversely, whether further investigations are required.


Transbronchial needle aspiration, transoesophageal fine-needle aspiration, mediastinoscopy, positron-emission tomography, computed tomography, Bayes’ theorem


Mediastinal staging in non-small-cell lung cancer (NSCLC) is crucial for correct prognosis and therapeutic choices. When no distal metastases are present, mediastinal involvement is the most important prognostic factor;1 therefore, mediastinal exploration represents an important resource-consuming step in patient evaluation. Ruling out mediastinal nodal involvement allows the patient to be considered for surgery; otherwise, complementary options such as chemotherapy or radiotherapy must be evaluated, subsequent surgery being suggested only when downstaging is achieved. The term clinical staging or pre-operative staging is commonly used in comparison with pathological staging, achieved during surgical intervention, which represents the gold standard in lung cancer staging.

Nowadays, several techniques are available for pre-operative mediastinal staging. The techniques can be separated into: imaging techniques, such as contrast-enhanced computed tomography (CT) and positron-emission tomography (PET); minimally invasive techniques, such as transbronchial needle aspiration (TBNA), endobronchial ultrasound (EBUS)-guided TBNA and endoscopic ultrasound (EUS)- guided fine-needle aspiration (FNA); and surgical techniques, such as mediastinoscopy, mediastinotomy and thoracoscopy.

Some of these techniques – PET, mediastinoscopy and EUS-FNA – provide very sensitive and specific results. TBNA alone, on the other hand, although highly specific, has not proved to be sufficiently sensitive and may provide false-negative results; its performance improves when supported by EBUS. Available Techniques Computed Tomography
Alongside standard chest X-ray, CT is currently considered the fundamental preliminary examination when evaluating lung cancer. Contrast-enhanced chest CT is highly accurate in detecting lymph node enlargement, although a high interobserver variability rate may exist.2 The literature reports good specificity of CT (about 80%) and moderate sensitivity (not above 60%).3 This may imply that an enlarged mediastinal lymph node (short axis ≥1cm) in a patient affected by lung cancer may in fact be healthy in four cases out of 10, whereas metastasis may be found in up to 20% of patients with normal size lymph nodes (short axis <1cm). Therefore, secondary neoplastic localisation cannot be diagnosed uniquely on the basis of the dimensions of the lymph nodes,4 and CT thus plays a central role in guiding the choice of the most appropriate procedure for node biopsy. Accordingly, the recent American College of Chest Physicians (ACCP) guidelines on mediastinal staging report that CT may be considered sufficient only in cases of massive mediastinal invasion; in any other cases, further diagnostic techniques should be implemented.5
Positron-emission Tomography
PET is probably the most revolutionary diagnostic technique of the last 20 years in the investigation of NSCLC.6–9 Its sensitivity and specificity are 75–91% and 78–93%, respectively, depending on lymph node size.10 Its overall sensitivity and negative predictive value are comparable to those of mediastinoscopy, such that mediastinal negativity on PET paves the way to the use of surgery with no need for further examinations.10–14 However, despite a small amount of reported false-negatives (5–8%), a recent meta-analysis showed that in patients with normal-sized lymph nodes the false-negative rate may reach 25%.15 This happens above all for central5,16,17 or large tumours1,18 or for tumours with an elevated standardised uptake value (SUV).18,19 Nevertheless, owing to its high performance, PET is considered the reference test for all potentially operable patients.20

Needle Aspiration Techniques
The use of TBNA in lung cancer staging has recently been steadily increasing. The sensitivity and specificity of this technique are around 76 and 98%, respectively.21 When rapid on-site examination (ROSE) is coupled with TBNA,22 the performance of TBNA increases owing to the shorter duration and lesser risks of the procedure according to some authors,23 or because of better accuracy according to others.24,25

When supported by other complementary techniques, such as EBUS, TBNA yield may improve, and its sensitivity may rise >90% when a convex probe is used, which allows direct observation of the needle piercing the lymph node.26–29 However, in clinical practice the worthwhile application of ultrasound appears limited to lymph nodes at American Thoracic Society (ATS) stations one and two (in such cases endoscopists have no definite safe landmarks for the puncture), to small lymph nodes (≤5mm) and when ROSE is not performed.30,31 Similar to TBNA, EUS-FNA provides high sensitivity and specificity; its major limitations are lymph nodes anterior to the trachea and to the main bronchi.32–34

As for other needle aspiration techniques, a positive result can be considered definitive for staging, while surgical confirmation is generally required in the event of a negative result.5,35 This assumption does not consider any qualitative evaluation of a non-diagnostic sample; in fact, to date no reliable criteria for distinguishing whether a sample comes from a lymph node or not have been identified. Martinez-Olondris et al. in a series of 194 patients demonstrated that the sensitivity of TBNA was 88% when the study included only adequate samples, namely samples with neoplastic cells or lymphoid cellularity.36 Others have proposed a score based on the number of lymphocytes on the slide; using EBUS-TBNA and accounting only for the samples with more than 40 lymphocytes per field (magnification x40), the authors produced only one false-negative.37 Therefore, we can suppose that using semi-quantitative criteria for evaluating adequacy can improve TBNA performance on healthy lymph nodes, modifying the value of a negative result in mediastinal staging.

Surgical Techniques
Surgical techniques are considered as a source of reference for the evaluation of suspicious lymph nodes following a negative or inadequate cytological result. Of the surgical techniques, mediastinoscopy is the gold standard in the pre-operative staging of lung cancer. Its sensitivity is high (75–90%) and complications are rare, although potentially severe.5,38–41 However, it can only reach the paratracheal stations (levels one, two and four) and the subcarinal station (level seven, anterior).5 In general, this technique is not popular among surgeons;42 in addition, the increasing availability and accuracy of ultrasound-guided minimally invasive techniques have been challenging the reference role of mediastinoscopy in recent years.43 Video-assisted thoracic surgery (VATS) can reach several mediastinal levels, in particular nodal stations five and six, but its sensitivity varies widely among series. The aorto-pulmonary window station five can be approached by Chamberlain’s anterior mediastinotomy when other techniques are not available or have failed.5Staging Protocols for Mediastinum
It is well known that in clinical stage N0, histology–cytology finds nodal metastases in up to 20–25% of cases.18,44,45 Unexpected mediastinal involvement (even without CT or PET abnormalities in the mediastinum) is more common if pathological hilar (N1) lymph nodes are present.18,46

Many risk factors for unforeseen mediastinal metastasis have been described,8,18,47–58 including tumour size, adenocarcinoma cell type, elevated levels of carcinoenmryonic antigen (CEA), central or right upper lobe location, tumour-related symptoms, patient age <65 years, tumour SUV >9–10 and pleural involvement. When risk factors are lacking, some authors suggest avoiding systematic lymph node dissection during surgical resection.59,60

The European Society of Thoracic Surgery (ESTS) recommends direct resort to surgery in cT1N0 tumours only for squamous cell carcinoma, and to mediastinoscopy for other cell types; in the other clinical stages, minimally invasive techniques (EBUS-TBNA, EUS-FNA) and, if negative, mediastinoscopy are suggested. When PET is available, surgery is advised in clinical stage 1, except in central tumours, adenopathies >1.6cm and tumours with a low SUV.1 However, observations that the probability of mediastinal metastasis rises in line with the tumour SUV value18,19 conflict with the ESTS position. The ACCP5 guidelines agree on avoiding further examinations in peripheral stage 1 tumours, but do not differentiate among cell types, and suggest cytological sampling irrespective of PET result when CT shows enlarged nodes and surgical confirmation of every negative needle aspirate. This argument is sometimes used due to the moderate negative predictive value of mediastinoscopy, which is not vastly different from that of EBUS-TBNA.61 As only patients with microscopic node involvement seem to benefit from surgery,62–69 many surgeons believe that CT and PET negativity on the mediastinum allows biopsy and surgery to be avoided, except in cases of T3 or adenocarcinoma, where mediastinal metastasis gives a poor prognosis. In addition, one must keep in mind that PET alone cannot easily distinguish between the central tumour and mediastinal metastasis.70–72

New Developments
Many of the mediastinal approaches discussed above take into account to some degree of the a priori probability that a given tumour will produce mediastinal metastasis, thus identifying different situations in which the same test can be conclusive for a surgical decision or, conversely, where the probability of occult mediastinal metastasis remains high even in the case of a negative result. Moreover, there is general agreement that a negative cytological result must always be confirmed surgically. However, only a few works have looked for objective criteria to distinguish a negative from an inadequate sample and have suggested different evaluation methods in the two cases.36,37 No work, to our knowledge, has ever tried to integrate the performance of all diagnostic tests and negative prognostic factors to build up one synthetic model in which the evaluation of negative results (including negative cytological results) is not absolute, but is related to pre-test data and therefore to the predictive value of the test. Recently,73 we suggested a mathematical model using Bayes’ theorem that enables the probability of nodal metastasis to be predicted after a certain number of diagnostic procedures has been performed, providing a simple way of evaluating when a patient can undergo surgery or, conversely, whether further investigations are required.

Figure 1 shows a flowchart focusing on a reasoned study of mediastinum using probability calculations. Figure 2 provides a simplified algorithm in which the pre-test probability of metastasis and the predictive value of each examination (in the case of a positive or negative result) are taken into account for each indicated choice. Surgery is considered a possible choice whenever the probability of mediastinal metastasis falls below 10%.

For example (see Figure 2), in peripheral T1, a CT-negative mediastinum indicates a <10% probability of metastasis; in this case, immediate resort to surgery may be considered reasonable. Positive CT indicates a probability of metastasis of up to about 40%; in this case, negative PET would authorise surgery (1–7% probability of mediastinal metastasis). Conversely, in clinical stage 2 (pre-test probability of mediastinal metastasis 40–60%), negative PET would not exclude with a sufficient safety margin the presence of mediastinal metastasis (probability 12–17%). Cytological study of the mediastinum must therefore be performed regardless of the PET result. Furthermore, if PET is positive, a negative cytology would not be sufficient and mediastinoscopy will be mandatory. As in any mathematical product, no matter which test (PET or TBNA) is performed first, the result will be the same. We can therefore identify three main clinical–radiological phenotypes in NSCLC (see Figure 3):

  • Phenotype a: The probability of mediastinal metastasis is <20%. In this case, negativity on either CT or PET authorises surgery.
  • Phenotype b: The probability of mediastinal metastasis is about 30–40%. In this case, surgery may be suggested when both CT and PET are negative.
  • Phenotype c: The probability of mediastinal metastasis is >40%. In this case, surgery is indicated only when both PET and cytology are negative. In any other case, surgical confirmation is necessary.

Mediastinal staging is crucial to ensure the best therapeutic option is chosen for each patient. A diagnosed stage N0 after CT and PET requires surgery, except in cases of unfavourable grading, large or central tumours or a very high SUV of the primary tumour, given the major probability of metastasis in the mediastinal lymph node even in the case of negative CT and PET. For the same reason, clinical stage N1 suggests the need for minimally invasive and/or surgical biopsy techniques. A negative result of a needle aspiration technique is not considered final since micro-metastasis remains a risk and plagued lymph nodes may be situated next to unaffected ones; therefore, a negative cytological sample generally requires surgical confirmation. However, diagnostic surgery could be avoided in the case of a low post-test probability of neoplastic localisation. To obtain this assessment we have developed a staging proposal on the basis of data provided by the literature and plain statistical concepts using Bayes’ theorem; the resulting algorithm may provide a rational opportunity to tackle the challenge of mediastinal staging in lung cancer. The application of this protocol would lead to a better use of available resources (in terms of costs/benefits) by enabling a more precise step-by-step analysis of the staging sequence. Although it may be accepted that irrational use of limited resources is unbearable, we may nonetheless consider that application of multiple (unnecessary) examinations may lead to ambiguity. Nevertheless, the suggested protocol represents a simulation based on statistical projections. We have started a clinical trial to validate our theoretical construct. ■

Article Information:

The authors have no conflicts of interest to declare.


Loris Ceron, Pulmonology Unit, Ospedale dell’Angelo, Via Paccagnella 11, 30174 Mestre-Venice, Italy. E:




  1. De Leyn P, Lardinois D, Van Schil PE, et al., ESTS guidelines for preoperative lymph node staging for non-small cell lung cancer, Eur J Cardiothorac Surg, 2007;32:1–8.
  2. Guyatt GH, Lefcoe M, Walter S, et al., Interobserver variation in the computed tomographic evaluation of mediastinal lymph node size in patients with potentially resectable lung cancer. Canadian Lung Oncology Group, Chest, 1995;107;116–9.
  3. Arita T, Matsumoto T, Kuramitsu T, et al., Is it possible to differentiate malignant mediastinal nodes from benign nodes by size? Reevaluation by CT, transesophageal echocardiography, and nodal specimen, Chest, 1996;110;1004–8.
  4. Kerr KM, Lamb D, Wathen CG, et al., Pathological assessment of mediastinal lymph nodes in lung cancer: implications for non-invasive mediastinal staging, Thorax, 1992;47:337–41.
  5. Detterbeck FC, Jantz MA, Wallace M, et al., Invasive mediastinal staging of lung cancer. ACCP evidence-based clinical practice guidelines (2nd edition), Chest, 2007;132:202–22.
  6. Vansteenkiste JF, Stroobants SG, De Leyn PR, et al., Mediastinal lymph node staging with FDG-PET scan in patients with potentially operable non-small cell lung cancer: a prospective analysis of 50 cases, Chest, 1997;112:1480–6.
  7. Poncelet AJ, Lonneux M, Coche E, et al., PET-FDG scan enhances but does not replace preoperative surgical staging in non-small cell lung carcinoma, Eur J Cardiothorac Surg, 2001;20:468–74.
  8. Farrel MA, McAdams HP, Herndon JE, Patz EF Jr, Non-small cell lung cancer: FDG-PET for nodal staging in patients with stage I disease, Radiology, 2000;215:886–90.
  9. Maziak DE, Darling GE, Inculet RI, et al., Positron emission tomography in staging early lung cancer. A randomized trial, Ann Intern Med, 2009;151:221–8.
  10. Vansteenkiste JF, Stroohants SG, De Leyn PR, et al., Mediastinal lymph node staging with FDG-PET scan in patients with potentially operable non-small cell lung cancer: a prospective analysis of 50 cases, Chest, 1997;112:1480–6.
  11. Poncelet AJ, Lonneux M, Coche E, et al., PET-FDG scan enhances but does not replace preoperative surgical staging in non-small cell lung carcinoma, Eur J Cardiothorac Surg, 2001;20:468–74.
  12. Farrel MA, McAdams HP, Herndon JE, Patz EF Jr, Non-small cell lung cancer: FDG-PET for nodal staging in patients with stage I disease, Radiology, 2000;215:886–90.
  13. De Langen AJ, Raijmakers P, Riphagen I, et al., The size of mediastinal lymph nodes and its relation with metastatic involvement: a meta-analysis, Eur J Cardiothorac Surg, 2006;29:26–9.
  14. Tasc E, Tezela C, Orkia A, et al., The role of integrated positron emission tomography and computed tomography in the assessment of nodal spread in cases with non-small cell lung cancer, Interact Cardiovas Thorac Surg, 2010;10:200–3.
  15. Gould MK, Kuschner WG, Rydzak CE, et al., Test performance of positron emission tomography and computed tomography for mediastinal staging in patients with non-small-cell lung cancer. A meta-analysis, Ann Intern Med, 2003;139:879–92.
  16. Scott WJ, Globar LS, Terry JD, et al., Mediastinal lymph node staging of non-small cell lung cancer: a prospective comparison of computed tomography and positron emission tomography, J Thorac Cardiovasc Surg, 1996;111:642–8.
  17. Verhagen AF, Bootsma GP, Tjan-Heijnen VC, et al., FDG-PET in staging lung cancer: how does it change the algorithm?, Lung Cancer, 2004;44:175–81.
  18. Cerfolio RJ, Bryant AS, Eloubeidi MA, Routine mediastinoscopy and esophageal ultrasound fine-needle aspiration in patients with non-small cell lung cancer who are clinically N2 negative, Chest, 2006;130:1791–5.
  19. Maedaa R, Isowaa N, Onumab N, et al., The maximum standardized 18F-fluorodeoxyglucose uptake on positron emission tomography predicts lymph node metastasis and invasiveness in clinical stage IA non-small cell lung cancer, Interact Cardiovasc Thorac Surg, 2009;9:79–82.
  20. De Wever W, Stroobants S, Coolen J, Verschakelen JA, Integrated PET/CT in the staging of nonsmall cell lung cancer: technical aspects and clinical integration, Eur Respir J, 2009;33:201–12.
  21. Harrow EM, Abi-Saleh W, Blum J, et al., The utility of transbronchial needle aspiration in the staging of bronchogenic carcinoma, Am J Respir Crit Care Med, 2000;161:601–7.
  22. Toloza EM, Harpole L, Detterbeck F, McCrory DC, Invasive staging of non-small cell lung cancer, Chest, 2003;123: 157S–166S.
  23. Baram D, Garcia RB, Richman PS, Impact of rapid on-site cytologic evaluation during transbronchial needle aspiration, Chest, 2005;128:869–75.
  24. Davenport RD, Rapid on-site evaluation of transbronchial aspirates, Chest, 1990;98:59–61.
  25. Diacon AH, Schuurmans MM, Theron J, et al., Utility of rapid on-site evaluation of transbronchial needle aspirates, Respiration, 2005;72:182–8.
  26. Herth F, Becker HD, Ernst A, Ultrasound-guided transbronchial needle aspiration. An experience in 242 patients, Chest, 2003;123:604–7.
  27. Silvestri GA, Hoffman BJ, Bhutani MS, et al., Endoscopic ultrasound with fine-needle aspiration in the diagnosis and staging of lung cancer, Ann Thorac Surg, 1996;61:1441–5.
  28. Herth F, Becker HD, Ernst A, Conventional vs endobronchial ultrasound-guided transbronchial needle aspiration, Chest, 2004;125:322–5.
  29. Herth FJ, Eberhardt R, Vilmann P, et al., Real-time endobronchial ultrasound guided transbronchial needle aspiration for sampling mediastinal lymph nodes, Thorax, 2006;61:795–8.
  30. Trisolini R, Lazzari Agli L, Patelli M, Conventional vs endobronchial ultrasound-guided transbronchial needle aspiration of the mediastinum, Chest, 2004;126;1005–6.
  31. Shannon JJ, Bude RO, Orens JB, et al., Endobronchial ultrasound-guided needle aspiration of mediastinal adenopathy, Am J Respir Crit Care Med, 1996;153:1424–30.
  32. Fritscher-Ravens A, Endoscopic ultrasound evaluation in the diagnosis and staging of lung cancer, Lung Cancer, 2003;41: 259–67.
  33. Micames CG, McCrory DC, Pavey DA, et al., Endoscopic ultrasound-guided fine-needle aspiration for non-small cell lung cancer staging, Chest, 2007;131;539–48.
  34. Vilmann P, Larsen SS, Endoscopic ultrasound-guided biopsy in the chest: little to lose, much to gain, Eur Respir J, 2005;25:400–1.
  35. Szlubowski A, Kuzdzał J, Kołodziej M, et al., Endobronchial ultrasound-guided needle aspiration in the non-small cell lung cancer staging, Eur J Cardiothorac Surg, 2009;35:332–6.
  36. Martínez-Olondris PP, Molina-Molina M, Xaubet A, et al., Punción transbronquial aspirativa en el estudio de las adenopatías mediastínicas: rentabilidad y coste-beneficio, Arch Bronconeumol, 2008;44:290–94.
  37. Alsharif M, Andrade RS, Groth SS, et al., Endobronchial ultrasound-guided transbronchial fine-needle aspiration, Am J Clin Pathol, 2008;130:434–43.
  38. Karfis EA, Roustanis E, Beis J, Kakadellis J, Video-assisted cervical mediastinoscopy: our seven-year experience, Interact Cardiovasc Thorac Surg, 2008;7:1015–8.
  39. Lemaire A, Nikolic I, Petersen T, et al., Nine-year single center experience with cervical mediastinoscopy: complications and false negative rate, Ann Thorac Surg, 2006;82:1185–9.
  40. Call S, Rami-Porta R, Serra-Mitjans M, et al., Extended cervical mediastinoscopy in the staging of bronchogenic carcinoma of the left lung, Eur J Cardiothorac Surg, 2008; 34:1081–4.
  41. Ebner H, Marra A, Butturini E, De Santis F, Clinical value of cervical mediastinoscopy in the staging of bronchial carcinoma, Ann Ital Chir, 1999;70:873–9.
  42. Little AG, Gay EG, Gaspar LE, Stewart AK, National survey of non-small cell lung cancer in the United States: epidemiology, pathology and patterns of care, Lung Cancer, 2007;57:253–60.
  43. Vilmann P, Puri R, The complete ‘medical’ mediastinoscopy (EUS-FNA + EBUS-TBNA), Minerva Med, 2007;98:331–8.
  44. Wallace MB, Ravenel J, Block MI, et al., Endoscopic ultrasound in lung cancer patients with a normal mediastinum on computed tomography, Ann Thorac Surg, 2004;77:1763–8.
  45. Meyers BF, Haddad F, Siegel BA, et al., Cost-effectiveness of routine mediastinoscopy in computed tomography- and positron emission tomography-screened patients with stage I lung cancer, J Thorac Cardiovasc Surg, 2006;131:822–9.
  46. Hishida T, Problems in the current diagnostic standards of clinical N1 non-small cell lung cancer, Thorax, 2008;63:526–31.
  47. Miller DL, Rowland CM, Deschamps C, et al., Surgical treatment of non-small cell lung cancer 1 cm or less in diameter, Ann Thorac Surg, 2002;73:1545–51.
  48. Riqueta M, Manac’ha D, Le Pimpec Barthesa F, et al., Prognostic value of T and N in non small cell lung cancer three centimeters or less in diameter, Eur J Cardiothorac Surg, 1997;11:440–4.
  49. Nonaka M, Kadokura M, Yamamoto S, et al., Tumor dimension and prognosis in surgically treated lung cancer: for intentional limited resection, Am J Clin Oncol, 2003;26: 499–503.
  50. Nirmal K, Veeramachaneni A, Richard J, et al., Risk factors for occult nodal metastasis in clinical T1N0 lung cancer: a negative impact on survival, Eur J Cardiothorac Surg, 2008;33:466–9.
  51. Takamochi K, Nagai K, Suzuki K, et al., Clinical predictors of N2 disease in non-small cell lung cancer, Chest, 2000;117: 1577–82.
  52. Suzuki K, Nagai K, Yoshida J, et al., Clinical predictors of N2 disease in the setting of negative computed tomographic scan in patients with lung cancer, J Thorac Cardiovasc Surg, 1999;117:593–8.
  53. Shafazand S, Gould MK, A clinical prediction rule to estimate the probability of mediastinal metastasis in patients with non-small cell lung cancer, J Thorac Oncol, 2006;1:953–9.
  54. Downey RJ, Akhurst T, Gonen M, et al., Preoperative F-18 fluorodeoxyglucose–positron emission tomography maximal standardized uptake value predicts survival after lung cancer resection, J Clin Oncol, 2004,22:3255–60.
  55. Cerfolio RJ, Bryant AS, Ohja B, Bartolucci AA, The maximum standardized uptake values on positron emission tomography of a non–small cell lung cancer predict stage, recurrence, and survival, J Thorac Cardiovasc Surg, 2005;130:151–9.
  56. Lee PC, Port JL, Korst RJ, et al., Risk factors for occult mediastinal metastases in clinical stage I non-small cell lung cancer, Ann Thorac Surg, 2007;84:177–81.
  57. Takizawa T, Terashima M, Koike T, et al., Lymph node metastasis in small peripheral adenocarcinoma of the lung, J Thorac Cardiovasc Surg, 1998;116:276–80.
  58. Al-Sarraf N, Aziz R, Gately K, et al., 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, 2008;33:104–9.
  59. Zhoua Q, Suzukia K, Anamia Y, et al., Clinicopathologic features in resected subcentimeter lung cancer – status of lymph node metastases, Interact Cardiovasc Thorac Surg, 2010;10:53–7.
  60. Fukui T, Katayama T, Ito S, et al., Clinicopathological features of small-sized non-small cell lung cancer with mediastinal lymph node metastasis, Lung Cancer, 2009;66:309–13.
  61. Tournoy KG, van Meerbeeck JP, New American College of Chest Physicians guidelines on mediastinal staging and management of stage IIIA –N2 non-small cell lung cancer: a European perspective, Pol Arch Med Wewn, 2008;118:175–8.
  62. Martini N, Flehinger BJ, The role of surgery in N2 lung cancer, Surg Clin North Am, 1987;67:1037–49.
  63. Goldstraw P, Mannam GC, Kaplan DK, Michail P, Surgical management of non-small-cell lung cancer with ipsilateral mediastinal node metastasis (N2 disease), J Thorac Cardiovasc Surg, 1994;107:19–27.
  64. Van Klaveren RJ, Festen J, Otten HJ, et al., Prognosis of unsuspected but completely resectable N2 non-small cell lung cancer, Ann Thorac Surg, 1993;56:300–4.
  65. Vansteenkiste JF, De Leyn PR, Deneffe GJ, et al., Survival and prognostic factors in resected N2 non-small cell lung cancer: a study of 140 cases. Leuven Lung Cancer Group, Ann Thorac Surg, 1997;63:1441–50.
  66. Okada M, Tsubota N, Yoshimura M, et al., Prognosis of completely resected pN2 non-small cell lung carcinomas: What is the significant node that affects survival?, J Thorac Cardiovasc Surg, 1999;118:270–5.
  67. Andre F, Grunenwald D, Pignon JP, et al., Survival of patients with resected N2 non-small-cell lung cancer: evidence for a subclassification and implications, J Clin Oncol, 2000;18:2981–9.
  68. De Leyn P, Schoonooghe P, Deneffe G, et al., Surgery for non-small cell lung cancer with unsuspected metastasis to ipsilateral mediastinal or subcarinal nodes (N2 disease), Eur J Cardiothorac Surg, 1996;10:649–54, discussion 654–5.
  69. Naruke T, Goya T, Tsuchiya R, Suemasu K, The importance of surgery to non-small cell carcinoma of lung with mediastinal lymph node metastasis, Ann Thorac Surg, 1988;46:603–10.
  70. Quint LE, Staging non-small cell lung cancer, Cancer Imaging, 2007;7:148–59.
  71. Patel V, Shrager JB, Which patients with stage III non-small cell lung cancer should undergo surgical resection, The Oncologist, 2005;10:335–44.
  72. Kelly RF, Tran T, Holmstrom A, et al., Accuracy and costeffectiveness of [18F]-2-fluoro-deoxy-D-glucose-positron emission tomography scan in potentially resectable nonsmall cell lung cancer, Chest, 2004;125:1413–23.
  73. Ceron L, Michieletto L, Zamperlin A, Mediastinal staging in lung cancer: a rational approach, Monaldi Arch Chest Dis, 2009;71:170–5.

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