Ann Thorac Surg 2003;75:1715-1718
© 2003 The Society of Thoracic Surgeons
Original article: general thoracic
The value of chest computer tomography and cervical mediastinoscopy in the preoperative assessment of patients with malignant pleural mesothelioma
J. Hugo Schouwink, MDa,e*,
Leo Schultze Kool, MD, PhDb,
Emiel J. Rutgers, MD, PhDc,
Frans A. N. Zoetmulder, MD, PhDc,
Nico van Zandwijk, MD, PhDa,
Marc J. v.d. Vijver, MD, PhDd,
Paul Baas, MD, PhDa
a Department of Thoracic Oncology, Amsterdam, The Netherlands
b Department ofRadiology, Amsterdam, The Netherlands
c Department ofSurgical Oncology, Amsterdam, The Netherlands
d Department ofPathology, The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands
e Department of Pulmonology, Medisch Spectrum Twente, Enschede, The Netherlands
Accepted for publication December 22, 2002.
* Address reprint requests to Dr Schouwink, Medisch Spectrum Twente, Department of Pulmonary Diseases, Postbus 50000, Enschede 7500 KA, The Netherlands
e-mail: j.schouwink{at}ziekenhuis-mst.nl
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Abstract
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BACKGROUND: Patients with localized malignant pleural mesothelioma (MPM) can be considered for surgical resection with or without additional treatment. For this approach it is imperative to select patients without mediastinal lymph node involvement. In this study cervical mediastinoscopy (CM) is compared with computer tomography (CT) scanning for its diagnostic accuracy in assessing mediastinal lymph nodes during preoperative workup.
METHODS: Computer tomography scans of the chest and CM were performed in 43 patients with proven unilateral MPM. The CT scans were reviewed by one radiologist and two chest physicians. At CM the lymph node samples were taken from stations Naruke 2, 3, 4, and 7. Computer tomography and CM results were compared with final histopathologic findings obtained at thoracotomy or, if this was not performed, at CM.
RESULTS: Computer tomography scanning revealed pathologic enlarged lymph nodes with a shortest diameter of at least 10 mm in 17 of 43 patients (39%). There was histopathologic evidence of lymph node metastases at CM in 11 of these patients (26%). This resulted in a sensitivity of 60% and 80%, a specificity of 71% and 100%, and a diagnostic accuracy of 67% and 93% for CT and CM, respectively.
CONCLUSIONS: Cervical mediastinoscopy is a valuable diagnostic procedure for patients with MPM who are considered candidates for surgical-based therapy. Results of CM are more reliable than those obtained by CT scanning. Our data confirm results of previous studies reporting that mediastinal lymph node involvement is a frequent event in MPM.
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Introduction
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The prognosis of patients with malignant mesothelioma is still grim. Survival figures have not improved over the last decades. Neither surgery, radiotherapy, nor chemotherapy has resulted in sufficiently consistent response rates or gain in survival to be advocated as standard treatment for this disease [1,2]. Although there are some claims that complete resection alone or in combination with adjuvant treatment modalities improve median survival [3–5], these results have not been confirmed by others [6–8].
Selection of patients most likely to benefit from an aggressive approach is of paramount importance but is difficult to achieve [9]. Performance status and histologic subtype were found to be associated with survival [10, 11]. Other factors indicative for a beneficial postoperative outcome have been poorly documented. Two retrospective studies suggested that intrathoracic lymph node metastases discovered during thoracotomy are associated with poor survival [12, 13].
In the preoperative workup of malignant pleural mesothelioma (MPM) patients, computer tomography (CT) scans of the chest and the upper abdomen are used to determine the extent of the primary tumor and possible involvement of lymph nodes. Enlarged nodes are not always clearly identified by CT due to adherence of the primary tumor and, moreover, it was believed that they are seldom involved [14]. Cervical mediastinoscopy (CM) is another well established method to assess mediastinal lymph nodes. In this retrospective study, the results of mediastinoscopy and CT scanning are compared for their diagnostic accuracy of detecting mediastinal lymph node metastases in patients with MPM, screened for potentially operable disease.
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Material and methods
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Forty-three patients with potentially resectable MPM were referred to the Netherlands Cancer Institute between 1996 and 1999 to be assessed for pleuropneumonectomy followed by intraoperative photodynamic therapy (PDT; or radiotherapy in 1 patient) [8, 15]. Patients with MPM and in good general condition (ECOG 0 or 1) were considered eligible for combination treatment after extensive workup including: roentgenogram and CT scan of the chest, transthoracic ultrasound cardiography, spirometry, ventilation-perfusion scanning, and CM. Four days after administration of the photosensitizer meta-tetrahydroxphenylchlorin (mTHPC), a pleuropneumonectomy with tumor resection was performed including extensive lymph nodes sampling. During the operative procedure the inner wall of the empty chest cavity was illuminated with monochromatic light of 652 nm [15]. After en-block resection, the lung with pleura and the tumor were examined microscopically and lymph nodes in or adjacent to the resected specimen were examined for the presence of metastatic disease.
Computer tomography scanning of the chest was always performed before CM. Lymph nodes at CT were considered pathologic if the shortest diameter was at least 10 mm on one or more images [16]. All scans were evaluated separately by three of the authors (J.H.S., L.S.K., and P.B.) and final judgment of the lymph node status was made by consensus. CM was carried out under general anesthesia to obtain histologic samples of lymph node stations Naruke 2, 3, 4, and 7 [17]. Twenty four of the CT scans were made in our institution, 19 in the referring hospital, and 25 of them were contrast enhanced. Eight scans were performed using a spiral technique.
Sensitivity, specificity, positive and negative predictive value, and accuracy were calculated in correlation with final histopathologic assessment of all lymph node stations considered accessible for CM, according to the method of Galen [18]. For patients who were operated on, calculations were based on judgment of lymph nodes resected at thoracotomy, when not operated on, CM findings were used.
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Results
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Characteristics of the 43 patients who underwent the two staging procedures are presented in Table 1.
Median survival after diagnosis was 12 months, after mediastinoscopy survival was 8 months. The mean interval between CT and CM was 32 days (range 1 to 81 days). CM revealed evidence of lymph node involvement in 12 of 43 patients (28%). Thoracotomy was performed in 25 patients. Six patients were not operated upon because of chest wall invasion (2 patients), invasion of the pericardium (1 patient), or the patient refused treatment (3 patients).
In 3 patients, four lymph nodes accessible by mediastinoscopy turned out to be positive at thoracotomy. Two lymph nodes were located at Naruke 4 right, one was positive and one was negative on CT scan. The other two were located at Naruke 7 and, again, one was positive and one was negative on CT scan. Metastases in intrathoracic lymph nodes, not accessible by CM, were found in 6 of the 25 operated patients. Subaortic, paraesophageal lymph nodes and nodes in the internal mammary lymph node chain were involved in 2 patients each.
Correlation between CT and CM was relatively poor (Table 2).
Lymph node metastases were diagnosed by CM in 6 patients who had no enlarged nodes on CT scan. Node stations involved in this subgroup were Naruke 2 right (1 patient), 2 left (1 patient), 4 right (1 patient), and 7 (3 patients). No contralateral mediastinal lymph node metastases were detected by CM. Sensitivity, specificity, and accuracy for CM were considerably better for CM than for CT (Table 3)
with 80%, 100%, and 93% for CM versus 60%, 71%, and 67% for CT, respectively. Pathologic lymph nodes were more frequently encountered on CT at Naruke 4 right than by mediastinoscopy (11 vs 2, Table 4).
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Table 3. Sensitivity, Specificity, Positive Predictive Value, Negative Predictive Value, and Accuracy of CT and CM
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The thoracotomy tumor positive lymph nodes were found in 3 patients after an initial negative mediastinoscopy. Locations were Naruke 2 right, 4 right, and 7 (2 patients). However, the interval between CM and thoracotomy was considerable in 2 of these patients (3 and 4 months).
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Comment
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Insight in the growth pattern of malignant mesothelioma has changed in recent years. In the past malignant mesothelioma was thought to remain localized for relatively long periods of time, with metastases occurring only in the latest phases of the disease [14]. However, Sugarbaker and colleagues [12] demonstrated that mediastinal lymph node metastases could be demonstrated in 25% of 52 patients during thoracotomy. Although the influence on survival of positive mediastinal lymph nodes has not been studied as extensively as in nonsmall cell lung cancer (NSCLC), three recent studies provided consistent evidence for this relationship. The presence of lymph node metastases, as well as the number of involved lymph nodes were found to be of prognostic importance [9, 13].
Our study is the first to describe a series of patients with MPM in which mediastinoscopy was used consistently as an eligibility criteria for surgery. In our opinion, patients with locally advanced disease (lymphoid involvement) are not good candidates for a surgical approach. Mediastinal lymph nodes, assessed by CM, were positive in 28% of our patients. At thoracotomy we found lymph node metastases in CM accessible nodes in another 3 patients. In 2 of these patients this could be explained by the long interval between CM and thoracotomy (3 and 4 months). Thus, in 33% of our patients, histologic evidence of malignant mesothelioma metastases in these nodes was found, confirming earlier data reported by Sugarbaker and colleagues [12]. Rusch and coworkers [13] demonstrated mediastinal lymph node involvement in 52% of 157 treated patients, and it may be concluded that lymph node metastases are much more common than what was just recently thought [14].
The role of CT in detecting mediastinal lymph node metastases in NSCLC is limited [19–21]. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy seem to be similar to our patients with MPM. A possible limitation in the analysis of the CT scans of our study is the restricted use of contrast. Metastases in intrathoracic lymph nodes not accessible by CM (such as intrapulmonary, internal mammary, and Naruke 5, 8, and 9) were detected in a small number of patients at thoracotomy.
Mediastinal lymph node involvement can be assessed with several other techniques. Magnetic resonance imaging (MRI) has not proven superior to CT with regard to information on mediastinal lymph node status. The only important additional information supplied by MRI during preoperative workup is evidence of tumor invasion in diaphragm, chest wall, or pericardium if present [22–24].
In NSCLC Fluorodeoxyglucose (FDG) positron emission tomography results have a high correlation with histopathologic findings in mediastinal lymph nodes, although reliability is poor when nodes are smaller than 1-cm diameter [21, 25]. With this technique metabolically active lesions are visualized and it has proven to be a sensitive method for identification of malignant mesothelioma in general [26]. It may also improve preoperative judgment of N2 disease in MPM, if the primary tumor is not located in the proximity of the mediastinum, but this specific indication has only been addressed anecdotally [26].
Recently endoscopic ultrasonography, when combined with fine needle aspiration, was reported to add useful diagnostic information about subcarinal and posterior mediastinal lymph nodes in NSCLC [27, 28]. This technique is promising because it provides information about lymph nodes that are unattainable for CM. The diagnostic usefulness of endoscopic ultrasonography for patients with MPM has not yet been addressed.
In summary, we conclude that CM is an important and valuable diagnostic procedure to assess disease extent in patients with MPM. Assessment of mediastinal lymph nodes with CM is more accurate than by CT. The use of CM will lead to an improvement in patient selection and may reduce the number of futile thoracotomies. Whether new techniques can provide better or additional information about mediastinal lymph node involvement in MPM has to be established.
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Acknowledgments
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The authors thank Henk Smit, who gathered most of the CT scans, and Fiona A. Stewart for her support and critical comments. This study was supported by a grant from the Dutch Cancer Foundation (Project NKI 97–1446).
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Abstract
Introduction
