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Journal of Clinical Oncology, Vol 24, No 33 (November 20), 2006: pp. 5339-5340 © 2006 American Society of Clinical Oncology. DOI: 10.1200/JCO.2006.08.8831
In ReplyDepartments of Thoracic Surgery and Pneumology, University Hospitals Leuven, Leuven, Belgium We thank Dr Van Schil and Dr Stamatis for their help to try to explain why the sensitivity of remediastinoscopy in our series was lower than reported in the literature. In their letter, they do not support our hypothesis that sensitivity and accuracy of remediastinoscopy could be related to the thoroughness of the initial mediastinoscopy. They suggest that the differences in results could be due to our use of the videomediastinoscope, whereas they used the less sophisticated regular mediastinoscope in their own study. In contrast with our study,1 which was a prospective experience on a consecutive set of 30 homogeneously defined patients over a period of 3 years, the study of Van Schil et al2 was a retrospective study on 27 remediastinoscopies after neoadjuvant therapy in a heterogeneous set of patients over a 7-year period. It is well known that retrospective use of routine care data in diagnostic research may cause various methodological problems. Apart from the well-known selection bias, a so-called work-up bias may also be in place; because the procedure under study (in this case remediastinoscopy) is indicated by and interpreted with knowledge of the preceding tests, the diagnostic value of the procedure is commonly overestimated.3 In Van Schil et al's report, eight of the 11 patients with positive remediastinoscopy had progression of disease with a higher number of positive lymph node stations at remediastinoscopy compared with the initial mediastinoscopy.2 In three cases (cases 1, 2, and 4), remediastinoscopy proved that four or more lymph node stations were positive though the initial mediastinoscopy was only positive at one lymph node station. Five patients even progressed to N3 disease. However, according to the article, all patients had a partial response on computed tomography (CT) scan after induction chemotherapy.2 Although it is widely accepted that CT scan is far from optimal for mediastinal restaging, it is very hard to believe that 30% of patients had progressed under induction chemotherapy while their CT scan showed a response. How do we explain these results reported by Van Schil et al? First, as mentioned, there may be selection and work-up bias. Second, not all mediastinal lymph node stations were sampled at the initial mediastinoscopy, resulting in less fibrosis and adhesions, and explaining their higher sensitivity and accuracy for remediastinoscopy. Finally, their hypothesis is that the regular mediastinoscope is so superior that mediastinal progressive disease can be found in 30% of the patients with a response on CT scan. The Essen group reported on a very large series of 165 patients who underwent remediastinoscopy after induction chemoradiotherapy.4 Adding radiotherapy to the induction scheme may even result in more fibrosis and adhesions. They report that the mean number of lymph node stations sampled at mediastinoscopy was 4.2, which demonstrates that a full mediastinal mapping was performed at initial mediastinoscopy. As suggested by Goldstraw, this suggests that the previous extensive nodal evaluation cannot completely explain the difference.5 However, this series was not prospective and consecutive. Patients from different study protocols were examined. Some patients had surgically unresectable stage IIIa and IIIb disease.6 In some protocols, only patients with N3 disease underwent remediastinoscopy.7 In their retrospective review of their experience over a15-year period with remediastinoscopy, N3 disease was present in 49 of 165 patients. Our series evaluated remediastinoscopy in a homogeneous set of patients with potentially resectable N2 disease based on thorough initial mediastinoscopy. From a technical point of view, it might be different (or easier) to prove persistant mediastinal disease if both the ipsilateral and contralateral nodes were positive. As discussed in the article by Stamatis et al,4 usually the left lateral tracheal wall is more free of adhesions and fibrosis. Moreover, it is well known that a higher disease prevalence and enrollment of patients with a more severe spectrum of disease are sources of variation in diagnostic studies, leading to an increased sensitivity.8 Since 1995, we have introduced videomediastinoscopy for mediastinal staging of non–small-cell lung cancer (NSCLC). We have published our technique and experience of videomediastinoscopy and remediastinoscopy.9 Over the years, videomediastinoscopy has internationally been accepted to give improved visualization and accuracy of mediastinal staging for NSCLC.10 As of publication, there are two types of videomediastinoscopes available. The scope from Wolf (Richard Wolf, Knittlingen, Germany) has two blades and the inferior valve may be opened and is indeed broader than the normal mediastinoscope. We performed the initial and remediastinoscopy with the Storz videomediastinoscope (K. Storz, Tuttlingen, Germany). At the tip, the diameter of this videomediastinoscope is only 1 mm larger in height and breadth than the regular mediastinoscope. The proximal end is 2 mm larger in height. Obviously, such small differences in caliber cannot be responsible for the additional fibrosis and adhesions. Van Schil and Stamatis suggest that our disappointing results could be explained by losing the three-dimensional view by looking on a monitor rather than straight through the mediastinoscope. We believe that the magnification and improved imaging largely compensates for this. If needed, the operator still has the option to look straight through the videomediastinoscope as well. But who of us would not use the benefits of magnification on the screen and improved visualization but would rather look through the thoracoscope, laparoscope, or videobronchoscope? After a short learning period, videomediastinoscopy is safely performed with a high accuracy.11 We now hear from Dr Stamatis that he is in favor for the normal scope, while he wrote 1 year ago in his article on remediastinoscopy: "although our experience with videoscopic remediastinoscopy is very limited, we think that the magnification of the optical field and a simultaneous use of more than 1 instrument may contribute to facilitate the preparation."4 The importance of mediastinal downstaging after induction therapy for patients with mediastinal lymph node involvement has been recognized for at least 10 years in many centers worldwide. Despite this, the merits of remediastinoscopy have only been documented by a few retrospective studies. Our study was a prospective study performed in a high-volume center with substantial experience in mediastinoscopy and remediastinoscopy.1 We evaluated the accuracy of remediastinoscopy after induction chemotherapy for a homogeneous group of patients with N2 disease proven by a complete initial mediastinoscopy. We continue to believe that remediastinoscopy is not a promising tool to evaluate these patients, as it remains difficult to perform a complete mediastinoscopy twice in the same patient. Efforts should be made to explore the value of other restaging techniques in this setting. Authors' Disclosures of Potential Conflicts of Interest The authors indicated no potential conflicts of interest. REFERENCES
1. De Leyn P, Stroobants S, De Wever W, et al: Prospective comparative study of integrated positron emission tomography–computed tomography scan compared with remediastinoscopy in the assessment of residual mediastinal lymph node disease after induction chemotherapy for mediastinoscopy proven stage IIIA-N2 non–small-cell lung cancer: A Leuven Lung Cancer Group study. J Clin Oncol 24
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-3339, 2006 2. Van Schil P, Van Der Schoot J, Poniewierski J, et al: Remediastinoscopy after neoadjuvant therapy for non-small cell lung cancer. Lung Cancer 37 : 281 -285, 2002[CrossRef][Medline] 3. Oostenbrink R, Moons KG, Bleeker SE, et al: Diagnostic research on routine care data: Prospects and problems. J Clin Epidemiol 56 : 501 -506, 2003[CrossRef][Medline] 4. Stamatis G, Fechner S, Hillejan L, et al: Repeat mediastinoscopy as a restaging procedure. Pneumologie 59 : 862 -866, 2005[CrossRef][Medline] 5. Goldstraw P. Selection of patients for surgery after induction chemotherapy for N2 non–small-cell lung cancer. J Clin Oncol 24
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-1149, 1999 7. Stamatis G, Eberhardt W, Pöttgen C: Surgery after multimodality treatment of non-small cell lung cancer. Lung Cancer 45 : S107 -S112, 2004 (suppl 2)[CrossRef][Medline] 8. Brenner H, Gefeller O: Variation of sensitivity, specificity, likelihood ratios and predictive values with disease prevalence. Stat Med 16 : 981 -991, 1997[CrossRef][Medline] 9. De Leyn P, Lerut T: Videomediastinoscopy. Multimedia Man Cardiothorac Surg 2005; DOI: 10.1510/mmcts.2004.000166 10. Venissac N, Alifano M, Mouroux J: Video-assisted mediastinoscopy: Experience from 240 consecutive cases. Ann Thorac Surg 76
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Copyright © 2006 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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