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Ann Thorac Surg 2006;82:2004-2009
© 2006 The Society of Thoracic Surgeons

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Original Articles: General Thoracic

Retrospective Analysis of the Clinical Performance of Anterior Mediastinotomy

Division of Thoracic Surgery, Department of Surgery, Foothills Medical Centre, University of Calgary, Calgary, Alberta, Canada

Accepted for publication June 9, 2006.

^_* Address correspondence to Dr Nechala, Room G33, Foothills Medical Centre, 1403-29th St NW, Calgary, Alberta T2N 2T9, Canada (Email: pnechala{at}yahoo.com).

	Abstract

Top Abstract Introduction Patients and Methods Results Comment Acknowledgments References

 
BACKGROUND: Accurate staging of patients with lung cancer is imperative in generating an appropriate treatment strategy. This study examined the clinical performance of anterior mediastinotomy in staging patients with suspected left upper lobe non-small cell lung cancer.

METHODS: This study was designed as a retrospective cohort. All patients with suspected left upper lobe cancer and otherwise normal computed tomography scan results were eligible. Patients with clinically unresectable disease (advanced disease or not fit for surgery) were excluded. After exclusions, 151 patients were stratified into two groups: 117 patients had cervical and anterior mediastinotomy as part of preoperative staging, and 34 had cervical mediastinoscopy only. The primary outcome was rate of preventable thoracotomy defined as thoracotomy during which either metastases to aortopulmonary or paraaortic lymph nodes, or mediastinal invasion was identified.

RESULTS: The rate of preventable thoracotomy for the anterior mediastinotomy arm was 4 (3.4%) of 117, compared with 1 (2.9%) of 34 for cervical mediastinoscopy-only arm (p = 0.99). The rate of morbidity in the anterior mediastinotomy arm was 8 (6.8%) of 117, compared with 2 (5.8%) of 34 for the cervical mediastinoscopy-only arm (p = 0.99). Anterior mediastinotomy patients stayed in hospital 1 day longer (p = 0.008). Anterior mediastinotomy was successful at harvesting one or more lymph nodes in 67% of patients. Five patients (4.3%) who underwent anterior mediastinotomy were spared a thoracotomy by identification of metastases to aortopulmonary lymph nodes.

CONCLUSIONS: In patients with suspected left upper lobe lung cancer and otherwise normal computed tomography scan results, anterior mediastinotomy does not significantly reduce the rate of preventable thoracotomy.

	Introduction

Top Abstract Introduction Patients and Methods Results Comment Acknowledgments References

 
Lung cancer is the leading cause of cancer related death for both men and women. The incidence of lung cancer cases is greater than prostate or breast cancer [1]. The treatment of non-small cell lung cancer depends on its stage at presentation, and thus, accurate staging is pivotal. Within the current, internationally accepted TNM staging system [2, 3], non-small cell lung cancer is divided into early and advanced, partly determined by involvement of lymph nodes in the mediastinum that are designated as N2. Generally, patients with early stage lung cancer are treated surgically, and patients with advanced lung cancer are treated with chemotherapy and possibly radiotherapy.

Several imaging methods available for assessing N2 lymph nodes, including computed tomography (CT) scan, fluorodeoxyglucose 18 positron emission tomography (PET) scan, and endoscopic ultrasonography. Despite the reported accuracy of these imaging methods, patients generally cannot be denied potentially curative resection from imaging alone. Invasive methods for assessing these lymph nodes include transbronchial fine needle aspiration (FNA), transesophageal FNA, transthoracic FNA, and surgical biopsy through cervical mediastinoscopy and anterior mediastinotomy. Histologic proof of cancer involvement of N2 lymph nodes prevents unnecessary thoracotomy and its associated morbidity [4].

Non-small cell lung cancers in the left upper lobe can spread to lymph nodes in the subaortic/aortopulmonary window (#5 position) and the paraaortic (#6 position) areas, both of which are classified as N2. Standard cervical mediastinoscopy does not assess these lymph nodes; however, four surgical procedures that do are (1) anterior mediastinotomy (Chamberlain procedure), (2) extended cervical mediastinoscopy, (3) thoracoscopy, and (4) biopsy at the time of thoracotomy.

Extended cervical mediastinoscopy is rarely used. It increases the risk of stroke and can result in fracture of the great vessels [5–7] Thoracoscopy is time consuming, requires one-lung ventilation, and disrupts virginal planes, thus increasing the difficulty of the subsequent thoracotomy. In contrast, anterior mediastinotomy is easier and safer than extended cervical mediastinoscopy and is simpler and quicker than thoracoscopy. In addition to sampling of #5 and #6 lymph nodes, anterior mediastinotomy can avoid the risks associated with unnecessary thoracotomy by assessing tumors suspected of invading the mediastinum or evaluating the pleural space of patients with tumors associated with a pleural effusion.

Anterior mediastinotomy is the subject of a small number of studies that examine its sensitivity and specificity with respect to metastatic involvement of #5 and #6 lymph nodes [8–11]. Accuracy studies are not designed to show the added benefit of a diagnostic test in the clinical management of patients. To date, there are no studies that assess anterior mediastinotomy by comparing two groups of patients, nor are there any studies that examine a patient-focused outcome. The objective of this study was to examine the clinical utility of anterior mediastinotomy in staging patients with suspected left upper lobe non-small cell lung cancer and examine its contribution to clinical decision-making. The study was designed to compare two staging strategies, one that uses anterior mediastinoscopy and one that does not.

	Patients and Methods

Top Abstract Introduction Patients and Methods Results Comment Acknowledgments References

 
This study was conducted with complete approval by the Chair of the Ethics Committee, Office of Medical Bioethics, Faculty of Medicine, University of Calgary. During the progress of the study, human subjects were not contacted, and all data were managed in an anonymous fashion. Individual patient consent was waived by the Chair of the Ethics Committee.

This was a retrospective cohort study. All patients referred to Foothills Medical Centre Thoracic Surgery service between January 1999 and December 2004 were reviewed. The starting point for this study was all patients who had a cervical mediastinoscopy. Because of the current standard of practice at our institution, any patient suspected of having a resectable non-small cell carcinoma would have undergone cervical mediastinoscopy. Mediastinoscopy, as a part of lung cancer staging, is conducted separate from resection to ensure that staging is as accurate as possible. Most mediastinoscopy patients in the past were kept overnight; however, recently cervical mediastinoscopy is being done on an outpatient basis.

At our center of four thoracic surgeons, #5 and #6 lymph nodes are assessed by two different approaches, thus allowing for an assessment of the clinical utility of anterior mediastinotomy. The first staging strategy includes anterior mediastinotomy for all patients with suspected left upper lobe lung cancer. The second staging strategy in patients with suspected left upper lobe lung cancer includes anterior mediastinotomy only if there is #5 or #6 lymphadenopathy by CT scan criteria or if mediastinal invasion is suggested on the CT scan. Thus, present within the group of patients with left upper lobe lung lesions and otherwise normal results on CT scans (no mediastinal adenopathy, no suspicion of mediastinal invasion) are two subsets of patients who are otherwise similar: those who underwent anterior and cervical mediastinoscopy as a part of their pre-operative staging and those who had cervical mediastinoscopy only.

Once all patients with left upper lobe lung lesions were identified, patients were further excluded if they had mediastinal adenopathy by CT scan criteria (more than 1 cm shortest axis), tumor involvement of N2 mediastinal lymph nodes by cervical mediastinoscopy, concerns on CT scan of mediastinal invasion, evidence of T4 disease at presentation other than mediastinal invasion, a pleural effusion, evidence of other pulmonary parenchymal masses, distant metastases at diagnosis, history of previous cancer, physiologically unfit for resection, patient opted for nonsurgical treatment, or if information was insufficient information (Table 1, Fig 1). In cases of discrepancy between the CT scan report and the surgeon’s impression of the CT scan, the original impression of the surgeon was taken as the final verity. Following the above exclusions, the patients were divided into two groups: those who were staged by cervical and anterior mediastinotomy and those staged by cervical mediastinoscopy only. The two groups were then compared.

View larger version (13K): [in this window] [in a new window]   Fig 1. Flow chart shows the patients selection process for the study.

Secondary outcomes included morbidity of anterior mediastinotomy, length of hospital stay, rate of successful lymph node harvest by anterior mediastinotomy, and the number of patients who avoided thoracotomy as a result of advanced disease identified by anterior mediastinotomy.

A two-tailed unpaired Student t test was used to compare continuous variables of age, tumor size, and length of hospital stay. A two-tailed Fisher exact test was used to compare the binomial variables of gender, rates of preventable thoracotomy, and morbidity. Difference in proportions (DIP) and associated 95% confidence intervals (CI) are also provided.

	Results

Top Abstract Introduction Patients and Methods Results Comment Acknowledgments References

 
Between January 1999 and December 2004, 1179 patients underwent cervical mediastinoscopy at the Foothills Medical Centre. Of these, 666 were excluded because lung lesions were on the right side, 120 were excluded because cervical mediastinoscopy was done for reasons other than suspected lung cancer (ie, mediastinal lymphoma, diagnosis of granulomatous disease), and 91 were excluded because the lesion was located in the left lower lobe. These exclusions left a remaining working of 302 patients with suspected left upper lobe non-small cell lung cancer.

From these 302, a further 151 were excluded because they met one or more of the exclusion criteria (Table 1). The remaining 151 patients were allocated to their respective cohorts, resulting in 117 patients who had an anterior mediastinotomy in addition to cervical mediastinoscopy as a part of their staging work-up, and 34 patients who had cervical mediastinoscopy only.

A comparison of the two cohorts reveals that they are not statistically different in terms of age, gender, and tumor size (Table 2). The results of the primary and secondary outcomes are summarized in Table 3. The rate of preventable thoracotomy for the anterior mediastinotomy arm was 4 (3.4%) of 117, compared with 1 (2.9 %) of 34 for controls (p = 0.99; DIP, –0.5%; 95% CI, –3.6% to 7.4%). A lower rate indicates that patients are less likely to have a preventable thoracotomy, and a negative difference in proportion indicates an outcome favoring the cervical mediastinoscopy-only arm.

	Comment

Top Abstract Introduction Patients and Methods Results Comment Acknowledgments References

The validity of our findings is challenged by the retrospective nature of the study design and the associated selection bias that threatens the validity of such studies. We have done our best to limit selection bias by starting with all patients who underwent cervical mediastinoscopy. The current practice standard at our institution makes it highly unlikely that a patient would be taken to thoracotomy before complete staging. By selecting all left upper lobe tumors from this large group of patients, it is highly unlikely that patients with different prognostic variables were selectively allocated to either the anterior mediastinotomy group or the cervical mediastinoscopy only group. Table 2 is reassuring in that it demonstrates no significant differences between groups; however, given the small sample size, a type II error is possible and a significant prognostic difference exists.

The retrospective nature of this study required the use of thoracotomy and mediastinal lymph node sampling as the reference standard against which anterior mediastinotomy was judged. Unfortunately, thoracotomy is itself not a perfect test. If this study were set up in a prospective fashion, all patients undergoing thoracotomy would have had a formal #5 and #6 lymph node dissection to provide a more robust reference standard. It is difficult to estimate the impact of this on the final analysis, but it is likely that any understaging of the mediastinum would be the same in both groups.

To make the study sample relevant to the study question, numerous exclusion criteria had to be applied. This has resulted in a small sample size and an underpowered study. An examination of the confidence interval associated with the primary outcome reveals that the difference in proportion might be as low as –3.6% or as high as 7.4%. For advocates of anterior mediastinotomy, the question becomes how many anterior mediastinotomies are worth averting one preventable thoracotomy. Should the real difference in proportion lie in the upper extreme of this confidence interval, it would imply that approximately 14 anterior mediastinotomies are required to prevent one thoracotomy for advanced disease; however, it is more likely that the real difference in proportion is closer to that of the observed value, which means that as many as 200 anterior mediastinotomies are required to prevent one thoracotomy for advanced disease.

Another weakness of this study is the technique of anterior mediastinotomy itself. We report a 67% rate of successful lymph node harvest (retrieval of 1 or more lymph nodes). Arguably, this rate seems low; however, despite an extensive search of the literature, no comparable figure could be found. Furthermore, if we examine the 4 patients in the anterior mediastinotomy group that had #5 lymph nodes discovered positive at the time of thoracotomy, 3 of them did have a successful biopsy of a #5 lymph node at anterior mediastinotomy. This suggests that the short comings of anterior mediastinotomy in staging #5 and #6 lymph nodes stem more from its ability to accurately sample a whole #5 lymph node rather than its ability to retrieve a lymph node.

Some thoracic surgeons believe that patients with metastatic disease involving #5 or #6 lymph nodes should undergo resection regardless of the results of the anterior mediastinotomy and therefore do not use anterior mediastinotomy as a part of their staging work-up. This is based on studies that report on prognosis of single-station metastases to #5 and #6 lymph nodes as being favorable compared with other N2 locations [12–14]. These studies, however, are all retrospective, small, predate wide use of CT scanning, or do not necessarily apply to a North American population.

Currently, we consider biopsy-proven metastatic carcinoma of #5 and #6 lymph nodes as N2 (advanced disease) and thus unresectable. This strict policy is based on several studies. The first and foremost is the most recent iteration of the non-small cell lung cancer staging system described by Mountain and colleagues [3, 4]. The second is the recently completed Intergroup Trial 0139, a phase III comparison of concurrent chemotherapy plus radiotherapy versus chemoradiotherapy, followed by surgical resection for stage IIIA (pN2) non-small cell lung cancer [15]. Even with the most recent update of this trial, there is no survival advantage by the addition of surgery to chemoradiotherapy for pN2 disease [16]. Two retrospective studies have also examined the prognosis of patients with pN2 non-small cell lung cancer [17, 18]. Specifically, they confirm the poor prognosis of these patients, especially when mediastinal lymph node involvement is discovered at mediastinoscopy rather than at thoracotomy.

Staging of the mediastinum for lung cancer is undergoing rapid change. FNA of N2 lymph nodes, whether transbronchial or transesophageal, is a recent staging modality. The reported sensitivity is approximately 90%, indicating that 10% of results are false-negative [19]. Nevertheless, in patients suspected of harboring mediastinal disease (ie, enlarged lymph nodes by CT scan criteria), FNA aspiration can avoid more invasive methods such as cervical or anterior mediastinoscopy. For this reason, we use FNA only in the setting of suspected mediastinal lymph node involvement. None of the 151 study patients underwent a FNA.

PET scanning is also an important staging modality whose sensitivity and specificity are 84% and 89% at best [20]. In a well-conducted clinical utility study (PET in LUng cancer Staging [PLUS] multicentre randomized controlled trial) that compared two staging strategies, one which used PET and the other did not, the primary outcome of futile thoracotomy was 21% in the PET scanning group compared with 41% in the non-PET group (p = 0.003) [21]. From these results, it is clear that the use of PET scanning in the staging of non-small cell lung cancer will continue to grow. The current study was conducted before the arrival of a CT/PET scanner and thus no patients in the study group had a PET scan. A small number of patients had out-of-region PET scans in the excluded group. Our believe that with routine use of PET scanning, the role of anterior mediastinotomy will be even more limited than demonstrated by our current study.

In conclusion, this study does not support the use of anterior mediastinotomy in the staging of patients with suspected left upper lobe non-small cell lung carcinoma and otherwise normal CT scans.

	Acknowledgments

Top Abstract Introduction Patients and Methods Results Comment Acknowledgments References

 
We acknowledge the data management support of Corina Tiruta.

	References

Top Abstract Introduction Patients and Methods Results Comment Acknowledgments References

 

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