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Ann Thorac Surg 2003;75:1102-1106
© 2003 The Society of Thoracic Surgeons

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Original article: general thoracic

Postinduction video-mediastinoscopy is as accurate and safe as video-mediastinoscopy in patients without pretreatment for potentially operable non–small cell lung cancer

^a Division of Thoracic Surgery, Inselspital Bern, Bern, Switzerland
^b Institute of Medical Oncology, Inselspital Bern, Bern, Switzerland
^c Department of Surgery, Centre Hôpitalier Universitaire Vaudois, Lausanne, Switzerland

Accepted for publication October 29, 2002.

^* Address reprint requests to Dr Lardinois, Division of Thoracic Surgery, University Hospital, Raemistrasse 100, 8091 Zurich, Switzerland
e-mail: didier.lardinois{at}chi.usz.ch

	Abstract

Top Abstract Introduction Material and methods Results Comment References

 
BACKGROUND: Prospective assessment of accuracy and safety of video-mediastinoscopy (VMS) in patients without pretreatment and those after induction therapy for potentially operable non–small cell lung cancer.

METHODS: Between 1996 and 1999, 219 patients underwent VMS at our institution: 195 patients without pretreatment and 24 after completion of induction therapy. Mediastinal lymph nodes were dissected and biopsied according to the American Thoracic Society (ATS) lymph node mapping system using a video-assisted approach. The accuracy of VMS was assessed for each patient according to the results obtained from mediastinal lymph node dissection (MLND) performed during lung resection.

RESULTS: Video-mediastinoscopy in patients without pretreatment revealed a sensitivity, specificity, and accuracy as compared with MLND of 87%, 100%, and 95.6%, respectively, and a procedure-related complication rate of 4% (8/195 patients). Video-mediastinoscopy in patients after induction therapy revealed a sensitivity, specificity, and accuracy of 81%, 100%, and 91% as compared with MLND, without apparent complications.

CONCLUSIONS: Video-mediastinoscopy performed after induction therapy for non–small cell lung cancer is as accurate as mediastinoscopy in patients without pretreatment and did not confer additional morbidity.

	Introduction

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Mediastinoscopy is well established as an invasive mediastinal staging procedure for patients with potentially operable non–small cell lung cancer (NSCLC) and allows histologic confirmation or exclusion of N2 or N3 disease in most patients [1–3]. Technical refinements achieved by using a video-assisted approach (video-mediastinoscopy [VMS]) have contributed to increased acceptance of the procedure by surgeons because of improved magnification of the dissection field and the possibility of on-line projection of the procedure for teaching purposes [1, 2].

Mediastinoscopy has experienced a renaissance due to the introduction of neoadjuvant treatment protocols and recognition of the limitations of noninvasive mediastinal staging by computed tomography (CT) scan [4–7]. The introduction of ¹⁸fluorodeoxyglucose-positron emission tomography (FDG-PET) for the staging of NSCLC has called into question the role of mediastinoscopy for mediastinal staging in many institutions [8, 9]. However, recent reports have demonstrated the need of appropriate mediastinal restaging after induction therapy to aid proper selection of patients likely to benefit from surgical resection [10]. In addition, a recent report demonstrated the limitation of PET scan for predicting residual N2 disease after induction therapy [11].

Invariably, thoracic surgeons will be involved more frequently in invasive mediastinal staging after induction therapy in patients with operable NSCLC. We hypothesized that VMS might allow for easier identification of lymph nodes requiring biopsy. Thus, this study was designed to evaluate the safety and efficacy of VMS in patients with potentially operable NSCLC without pretreatment and in those after completion of neoadjuvant chemotherapy.

	Material and methods

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All patients with potentially operable NSCLC undergoing VMS for mediastinal staging before resection at our institution between 1996 and 1999 were enrolled. Exclusion of distant metastases was performed by CT scan or magnetic resonance imaging of the chest, upper abdomen, and the brain, and by bone scintigraphy. None of the patients were investigated by PET scan. This series included patients without pretreatment and patients who had received neoadjuvant chemotherapy without mediastinoscopy at other institutions who were then referred for resection in case of response.

Video-mediastinoscopy was performed with the classic cervical approach as described previously [1] and a specially designed video apparatus (Video-mediastinoscope, Wolf, Germany). Mediastinal lymph nodes were identified and dissected under video-endoscopic view according to the American Thoracic Society (ATS) lymph node mapping [12]. The following nodes were routinely dissected and biopsied in every patient: ATS level 7 (subcarinal), 4 (lower left and right paratracheal), and 2 (right paratracheal). Each biopsy was sent separately for examination. One part of the material was used for frozen section and the remaining tissue was processed for conventional histology. Patients without pretreatment and with suspect nodes ATS 5 (aortopulmonary window) and 6 (mediastinal anterior) on CT scan (more than 1 cm on its shortest axis) underwent exploration and biopsy by thoracoscopy during the same intervention, when mediastinoscopy revealed an absence of pathologic findings. Mediastinoscopy in pretreated patients was always performed by the same surgeon.

Patients without pretreatment and without evidence of lymph node metastases on frozen section underwent lung resection with formal mediastinal lymph node dissection (MLND) during the same intervention. Patients with N3 disease were excluded from further surgery. Patients with N2 disease received three cycles of docetaxel–cisplatin-based induction chemotherapy and underwent lung resection and MLND in case of clinical response, without repeat mediastinoscopy.

Patients who were referred for surgery from other institutions after completion of neoadjuvant chemotherapy underwent VMS, lung resection, and MLND during the same intervention if N3 disease was excluded on frozen section.

Mediastinal lymph node dissection consisted of formal en bloc dissection of all lymphatic tissue ATS levels 2, 3, 4, 7, 8, 9 on the right side, and of ATS level 4, 5, 6, 7, 8, 9 on the left side according to Martini and coworkers [13]. Each level was separately sent for examination and processed for conventional histology.

In each patient, the preoperative CT scan was assessed for mediastinal lymph node enlargement and correlated with the pathologic findings of the corresponding lymph node level according to the ATS mapping that emerged from VMS biopsy [12]. Mediastinal lymph nodes were considered pathologic on preoperative CT scan when they were larger than 1 cm in the shortest axis.

In each patient undergoing resection, the histologic result of each ATS level biopsied at VMS was correlated with that from the corresponding ATS level obtained after MLND.

Statistical analysis included determination of sensitivity, specificity, and accuracy of VMS in comparison with MLND in the two groups of patients.

	Results

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Between 1996 and 1999, 219 patients (178 men, 41 women; mean age, 63 years; range 34 to 80 years) underwent VMS for potentially operable NSCLC. The procedure was performed in 195 patients without pretreatment and in 24 patients after completion of induction therapy. Squamous cell carcinoma, adenocarcinoma, and large cell carcinoma were observed in 123 (56.2%), 62 (28.3%), and 34 (15.5%) of the patients, respectively. Staging after mediastinoscopy revealed stage IA in 11 patients (5%), IB in 59 (27%), IIA in 7 (3%), IIB in 35 (16%), IIIA in 61 (28%), and IIIB in 46 (21%). Positive mediastinal lymph nodes were detected by VMS in 63 of the 219 patients (28.8%). Of these 63 patients, 47 (21.5%) had N2 disease and 16 (7.3%) had N3 disease. Of the patients with N2 disease, single-level and multilevel N2 disease were noted in 83% and 17%, respectively. Lung resection and MLND were performed in 183 patients (83.5%). No resection was performed in 16 patients because of N3 disease, in 4 patients because of progressive disease after neoadjuvant treatment, and in 16 patients because of nonresectable disease found at thoracotomy.

Table 1 shows the correlation between the T status of the primary tumor and mediastinal lymph node involvement (N2 or N3 disease) found at VMS or MLND in patients without pretreatment. The patients after induction therapy were not included in this analysis, because of possible migration of T status after induction therapy. Although the incidence of mediastinal lymph node involvement increased with increasing T status, 18% and 8% of the T1/T2 tumors were associated with N2 and N3 disease, respectively, in patients without pretreatment.

No deaths were recorded within 30 days after VMS. Procedure-related complications were observed in 8 of 219 patients (3.7%), including left recurrent nerve palsy in 3 (1.4%), vascular lesions in 3 (1.4%), esophagus injury in 1 (0.45%), and wound infection in 1 (0.45%), but no complication was observed in patients who had prior induction therapy. Of the left recurrent nerve palsy cases, one was transient and the other two were treated by vocal cord medialization. Vascular lesions were found in the azygos vein, the innominate vein, and the brachiocephalic trunk, respectively. Successful repair of these vascular injuries followed by lobectomy and MLND was performed through a hemi-clamshell incision in all 3 patients without further sequelae. The esophageal injury occurred in a patient with centrally located left-sided NSCLC and ventral displacement of the esophagus, successfully treated by left pneumonectomy, suture of the esophagus, and mediastinal reinforcement by intrathoracic latissimus dorsi transposition.

	Comment

Top Abstract Introduction Material and methods Results Comment References

 
The introduction of FDG-PET scan and of neoadjuvant treatments have in part modified diagnostic and thera-peutic strategies for patients with potentially operable NSCLC. Positron emission tomography has shown an increased capability of detecting previously unsuspected distant metastases and higher sensitivity and specificity than CT scan for mediastinal lymph node assessment [9, 14, 15]. Given the high negative predictive value of PET, some researchers have suggested performing mediastinoscopy only in patients with positive mediastinal lymph nodes at PET scan [8, 16]. However, microscopic mediastinal lymph node disease might be underestimated by PET evaluation because of the inability of PET to detect lesions smaller than 5 mm [8, 9]. Moreover, PET has shown a significantly lower accuracy of mediastinal staging among patients who have undergone induction therapy than among patients without pretreatment, with a sensitivity of 67% and specificity of 61% being reported [11].

Neoadjuvant treatments are being used increasingly in patients with potentially operable NSCLC and several prospective studies have suggested a benefit for stage IIIA N2 disease [4, 5, 17, 18]. However, several reports have suggested that postinduction resection may be indicated only in patients with pathologic mediastinal downstaging after induction therapy [10, 18]. Pathologic mediastinal downstaging from N2 to N0/N1 has shown to be one of the most powerful predictors of survival [10] after resection following induction therapy. In addition, resection following induction therapy may increase postoperative morbidity and mortality compared with resection alone [5]. As a consequence, adequate mediastinal staging is mandatory not only for patients with potentially operable NSCLC requiring resection without pretreatment, but also for those considered for resection following induction. Because PET scan has a high accuracy in patients without pretreatment and low sensitivity and specificity after induction in this respect, mediastinoscopy might be considered more frequently after completion of induction therapy in the future. A video-assisted mediastinoscopic approach has recently been designed to improve magnification, techniques for dissection, and teaching [1, 2]. Improved visualization of the mediastinal structures might indeed facilitate invasive mediastinal staging after induction therapy because it may allow for a better identification of lymphatic tissue to be biopsied within tissue alterations frequently seen after induction. However, VMS has not been validated for this use. This study was designed to assess the value and safety of VMS for potentially operable NSCLC in patients without pretreatment and patients after completion of induction therapy.

Our results in patients without pretreatment revealed a sensitivity of VMS similar to that described in the literature (87% versus 80% to 94%), but a higher complication rate (3.7% versus 1% to 2%) [6, 7, 19]. However, these findings may not be related to the video-assisted technique per se, but rather to fact that VMS is mainly performed as a teaching procedure in patients without pretreatment at our institution. In fact, no major complication was observed after VMS performed by the same surgeon in patients after induction therapy. These life-threatening complications were successfully managed in all patients by liberal use of a hemi-clamshell approach and control of mediastinal bleeding, with simultaneous resection if indicated or justified.

T1 or T2 tumors were frequently associated with mediastinal lymph node disease in our patients with potentially operable NSCLC without pretreatment. In fact, patients with T1/T2 tumors revealed N2 and N3 disease found at VMS or operation in 18% and 8%, respectively. Several other reports also showed a high incidence of mediastinal lymph node metastases in patients with T1/T2 tumors varying between 15% and 25% [6, 20, 21]. These findings endorse the impression that CT scan is not accurate for mediastinal staging in patients with potentially operable NSCLC and that invasive mediastinal staging or PET scan should be used in T1 and T2 tumors as well.

Computed tomography scan revealed a lower accuracy in patients undergoing mediastinal staging after completion of induction therapy than among patients without pretreatment in our series. In contrast, the sensitivity, specificity, and accuracy of VMS in patients after induction was similar to that observed in patients without pretreatment, without any complications being observed. However, mediastinoscopy was not repeated in this series of patients. Repeat mediastinoscopy has been performed in small series of patients without additional morbidity and a sensitivity, specificity, and accuracy of 87.5%, 100%, and 93.5%, respectively [22–24].

In conclusion, mediastinal lymph node involvement is an important prognostic indicator in patients with potentially operable NSCLC with and without pretreatment and has an important implications for treatment selection. In patients without pretreatment, accurate mediastinal staging should be performed either by mediastinoscopy or PET scan (followed by mediastinoscopy in case of positive mediastinal PET findings). This recommendation also applies for T1/T2 tumors given the high incidence mediastinal involvement in T1/T2 NSCLC. Mediastinoscopy performed by use of a video-assisted approach after induction therapy is as accurate as mediastinoscopy in patients without pretreatment and does not confer additional morbidity to that expected from routine mediastinoscopy.

	References

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