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Ann Thorac Surg 1995;60:1337-1340
© 1995 The Society of Thoracic Surgeons

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Original Articles: General Thoracic

Thoracoscopic Staging of Esophageal Cancer: A Prospective, Multiinstitutional Trial

Division of Thoracic Surgery, Department of Surgery, University of Maryland Medical System, Baltimore, Maryland, Division of Thoracic Surgery, Brigham and Women's Hospital, Boston, Massachusetts, and Medical University of South Carolina, Charleston, South Carolina

	Abstract

Top Footnotes Abstract Introduction Material and Methods Results Comment Acknowledgments References

 
Background. Lymph node metastasis has been shown to be an important prognosticator in esophageal cancer. A prospective, multiinstitutional study of thoracoscopic lymph node staging in patients with biopsy-proven esophageal cancer was undertaken at University of Maryland, Medical University of South Carolina, and Brigham and Women's Hospital.

Methods. Forty-nine patients underwent thoracoscopic staging between September 1991 and August 1993. Five procedures were incomplete due to adhesions. Preoperative computed tomography, magnetic resonance imaging, esophageal ultrasound, and bronchoscopy were performed. After our initial experience with the left side of the chest, thoracoscopic staging was done through the right side of the chest unless specific indications dictated otherwise. Beginning in January 1993 routine laparoscopic/mini-laparotomy lymph node staging of the celiac axis was performed.

Results. Satisfactory thoracoscopic lymph node staging was achieved in 44 patients (95%). Of 33 patients undergoing esophageal resection, 29 were correctly staged (88%). Since initiating concomitant laparoscopic lymph node staging, we have correctly staged all of the last 9 patients with regard to celiac lymph nodes as well. Information regarding T status obtained at thoracoscopy was as follows: 3 patients were correctly ``downstaged'' to T3 despite preoperative noninvasive tests suggesting T4. In 2 patients thoracoscopy correctly predicted T4 invasion, whereas in 2 patients, thoracoscopy missed T4 lesions.

Conclusions. Thoracoscopy is a valuable tool for staging intrathoracic tumors. Preoperative staging of esophageal cancer may allow better allocation of adjuvant therapy. This pilot study suggests that thoracoscopic staging can correctly predict thoracic lymph node status with high accuracy and aid in better defining T status.

	Introduction

Top Footnotes Abstract Introduction Material and Methods Results Comment Acknowledgments References

 
See also page 1340.

Recent studies have suggested improved short-term survival with excellent response rates with combined chemotherapy, radiation, or chemotherapy/radiation therapy protocols followed by operation for esophageal cancer [1]. These reports also indicate high morbidity and mortality associated with combination therapy. Lymph node invasion has been shown to be an important independent predictor of prognosis in patients with esophageal cancer [2]. Prognosis in patients with esophageal cancer can be stratified according to depth of invasion and presence or absence of lymph node spread using the TNM or WNM classifications [3].

Preoperative staging of esophageal cancer would allow prospective prognostication. This might allow allocation of adjuvant therapy with its associated risks to groups with otherwise poor survival and avoid unnecessary morbidity. We evaluated the technical feasibility, safety, and accuracy of thoracoscopic and laparoscopic lymph node staging for patients with esophageal cancer in a multiinstitutional pilot study.

	Material and Methods

Top Footnotes Abstract Introduction Material and Methods Results Comment Acknowledgments References

 
Three institutions belonging to the Cancer and Leukemia Group B including University of Maryland Medical Center, Medical University of South Carolina and Brigham and Women's Hospital, undertook a pilot study to prospectively evaluate thoracoscopic and laparoscopic lymph node staging for esophageal cancer.

All patients had endoscopically biopsy proven carcinoma of the thoracic esophagus (>20 cm from the incisors). Computed tomographic (CT) scans were obtained routinely. Esophageal ultrasound (EUS) and magnetic resonance imaging (MRI) were performed when available. Bronchoscopy was performed on all patients with tumors adjacent to the carina or bronchi.

Thoracoscopy was performed using a technique previously described [4]. Lymph nodes (LNs) were sampled after incising the mediastinal pleura overlying the esophagus from the apex to the diaphragm. Lymph node stations were identified according to the terminology described by Casson and associates [5]. After the initial 14 patients were staged through the left side of the chest, thoracoscopy was thereafter done through the right side of the chest. This allowed maximal dissection of paraesophageal LNs, avoiding the aortic arch (unless noninvasive studies showed enlarged aortopulmonary window LNs [level 5 or 6]). After thoracoscopic staging was completed, laparoscopic or mini-laparotomy staging was performed using a standardized technique [6]. Four or five ports were placed in the epigastrium. The liver was retracted laterally, and the lesser omentum was opened with a cautery/scissors. Biopsy of LNs along the lesser curvature and the celiac axis was performed, using clips for hemostasis.

Esophageal resections were done by either Ivor Lewis esophagogastrectomy, combined laparotomy/thoracotomy with neck anastamosis, or left thoracotomy esophagogastrectomy. Transhiatal esophagectomy was avoided in this series to assure maximal LN sampling.

Preresection LN pathologic findings were compared with findings at esophageal resection. Statistical analysis included calculation of sensitivity and specificity as well as positive predictive and negative predictive values for each staging technique.

	Results

Top Footnotes Abstract Introduction Material and Methods Results Comment Acknowledgments References

 
Forty-nine patients underwent attempted thoracoscopic LN staging for esophageal cancer. There were 48 male patients and 1 female patient. Forty-one patients had squamous cell carcinoma and 8 patients had adenocarcinoma. The mean operating time was 2.5 hours (this often included a concomitant feeding jejunostomy, mediport placement, or both). Although cost was not analyzed in this study, an average of 8 disposable items were used per case (by averaging cost to institution, this runs approximately $400 per case).

Five patients had severe adhesions and therefore the procedure was aborted. Forty-four patients had successful thoracoscopic staging. Eight patients refused surgical resection, and 3 patients had inoperable disease due to pulmonary metastasis (2) or portal hypertension (1). Thirty-three patients therefore went on to surgical resection after thoracoscopic staging. These patients form the basis of the statistical analysis.

Findings at thoracoscopic lymph node staging showed N1 disease in 2 patients and N0 disease in 31 patients. Three of the 32 patients who had N0 disease (no positive nodes) at thoracoscopy were, in fact, found to have N1 disease at resection. One patient was downstaged from N1 at thoracoscopy to N0 at resection after neoadjuvant therapy. The sensitivity of thoracoscopy was therefore approximately 40%. The specificity, however, was 100% as there were no false positives. The positive predictive value was likewise 100%, and the negative predictive value was approximately 90% (Fig 1).

View larger version (48K): [in this window] [in a new window]   Fig 1. . Accuracy of thoracoscopic staging of lymph nodes (TSLN). (CT = computed tomographic; EUS = esophageal ultrasound; MRI = magnetic resonance imaging; NPV = negative predictive value; PPV = positive predictive value.)

Noninvasive staging tests were evaluated for their ability to predict LN stage. Computed tomographic scan had a sensitivity of 70% and specificity of 60%. Magnetic resonance imaging, on the other hand, had a sensitivity of 100% but a specificity of 60%. In this series EUS was 40% specific. All of the noninvasive tests tended to overstage LN involvement.

Additional information regarding depth of invasion and metastatic spread was obtained at thoracoscopy. Three patients who were clinically staged T4 by noninvasive tests (CT, MRI, EUS) were in fact found to have T3 lesions at thoracoscopy and subsequently underwent esophagectomy. Two patients underwent thoracoscopy that correctly predicted T4 invasion of the aorta and trachea and therefore did not go on to resection. In 2 patients thoracoscopy missed T4 lesions involving the trachea. One patient, who had questionable pulmonary metastasis on CT and MRI, was found to have definite pulmonary metastasis at thoracoscopic lung biopsy.

There were no deaths. One patient had a postoperative stroke. In 1 patient a pneumothorax developed requiring chest tube insertion. In 2 patients postoperative wound infections developed.

At the time of operation mediports were placed in 5 patients and jejunostomies in 6 patients in preparation for pre-resection chemotherapy/radiation and nutrition.

	Comment

Top Footnotes Abstract Introduction Material and Methods Results Comment Acknowledgments References

 
The extension of esophageal cancer to regional LNs portends a poor prognosis. Despite lack of evidence of metastatic spread by routine noninvasive testing, the pathologic stage determined after resection is frequently advanced. In part, this is due to the predilection for esophageal carcinoma to involve LNs without gross LN enlargement. In a study by Picus and associates [7], 40 of 43 surgically resected metastatic nodes and 68 of 84 resected normal nodes measured less than 7 mm in diameter. Unlike lung cancer, where more invasive staging, ie, mediastinoscopy, can be directed by LN size as measured by the CT scan, there is no uniform noninvasive approach to assess the true preoperative LN status in esophageal cancer patients [8, 9].

The frequency of LN involvement is estimated to be approximately 60% at the time of thoracotomy in patients with esophageal cancer; the percentage increases as tumor length reaches 5 cm or greater [10]. The pattern of lymph node spread is diverse and has been mapped by Akiyama and associates [11]. Most patients in his series had tumor spread to at least one thoracic LN station regardless of the level of the tumor. Patients with midesophageal cancers had positive abdominal lymph nodes in 45% of cases.

Noninvasive staging of esophageal cancer has included CT, MRI, and EUS. Computed tomographic evaluation is hampered by normal variation of nodal size, inflammatory enlargement, and metastatic involvement in normal-sized LNs [12]. Markland and colleagues [13] found that CT scans were falsely negative for mediastinal adenopathy in 18 or 34 patients with esophageal cancer. Although MRI has not been used extensively in esophageal carcinoma, early data do not show improvement in staging over CT scanning [14]. Esophageal ultrasound is highly accurate in detecting the depth of tumor invasion [15]. Although EUS is an improvement over CT, it has proved difficult to distinguish large inflammatory LNs from nodes with metastatic disease using EUS [16]. Specificity of EUS assessment of LN metastases has varied from 70% to 77% [18, 19]. The accuracy of EUS in assessing LN metastases appears to increase with advancing depth of invasion. Esophageal ultrasound is still only an indirect measure of LN involvement, however, and is not equivalent to histologic assessment. It also fails in a significant number of patients secondary to obstruction (26% to 62%) [16, 17].

Although the number of patients with N1 disease was low in this study, we believe this is a real finding because all patients had complete lymphadenectomy at resection. The patients with ``missed'' N1 disease are worrisome but may represent a learning curve. Among the three institutions participating one had 1/32 false negative, one had 1/9 false negative, and one had 2/9 false negatives. Clearly, as complete an LN sampling as possible should be performed.

The average hospital stay after a staging procedure was 2 to 3 days. We often use this stay for oncology and radiation therapy consultation. The majority of operating room costs for this procedure can be absorbed when performing a concomitant feeding jejunostomy or subcutaneous infusion port placement. In this way, too, thoracoscopic staging would rarely delay appropriate treatment, allowing pre-resection chemotherapy or even neoadjuvant chemotherapy/radiation therapy to be given with known definitive LN staging.

In a study by Murray and co-workers [20] in 1977, 30 patients underwent mediastinoscopy and mini-laparotomy. Five patients were found to have positive paratracheal LNs and 16 patients were found to have positive celiac lymph nodes. The use of surgical staging in esophageal cancer would at present seem to be the best way to accurately judge LN status. Thoracoscopy is a minimally invasive procedure that allows one the possibility of staging LNs along the whole length of the esophagus from the apex to the diaphragm. At the same setting local spread of disease and evidence of unresectability (such as pulmonary metastases) can be assessed. Laparoscopy has been used to rule out liver and lymph node metastases in patients with esophageal cancer [21]. Although this has not been adopted widely, the addition of laparoscopy would allow one the ability to assess celiac and left gastric nodes. This report shows that thoracoscopy offers the potential of pre-resection surgical staging for esophageal cancer with no mortality and minimal morbidity.

The use of surgical staging to document mediastinal node involvement is now considered routine and a prerequisite to the institution of neoadjuvant therapy for lung cancer. A minimally invasive test that can make a correct prognosis in patients with esophageal cancer could be used to allocate chemotherapy/radiation therapy to the appropriate patient populations and reduce treatment morbidity and mortality. It would also allow accurate assessment of the effect of neoadjuvant therapy on stage IIB and III disease. The goal of using preoperative, minimally invasive staging in esophageal cancer would be to assign patients to appropriate, specific disease stage groups before resection. The impact of obtaining this kind of data will depend to a large degree on the surgical philosophy vis-à-vis resection for esophageal cancer. The finding of T4 tumors with invasion of the trachea or aorta would obviously militate against surgical resection. The finding of positive LNs may sway some surgeons away from resection (especially with positive celiac lymph nodes). Other surgeons may decide on a radical resection with concomitant lymphadenectomy using this kind of information. In this era of multimodality therapy, one would suspect that the patients with positive LNs would be selected for pre-resection, neoadjuvant chemotherapy and radiation therapy such as is currently done in the Intergroup Esophageal Trial. Those patients who have negative LNs or who have only T1 lesions may be considered for resection only. This would then avoid the unnecessary morbidity of trimodality therapy to all patients and allow therapy for esophageal cancer to be stage-specific as is currently being done in lung cancer.

This study demonstrates the feasibility and safety of thoracoscopic and laparoscopic LN staging. The efficacy, accuracy, and cost of minimally invasive surgical staging of esophageal cancer will be further studied in a multiinstitutional, prospective setting (CALGB 9380).

	Acknowledgments

Top Footnotes Abstract Introduction Material and Methods Results Comment Acknowledgments References

 
Supported in part by CALGB U-10 grant 59594 from the National Institutes of Health.

	Footnotes

Top Footnotes Abstract Introduction Material and Methods Results Comment Acknowledgments References

 
Presented at the Poster Session of the Thirtieth Annual Meeting of The Society of Thoracic Surgeons, New Orleans, LA, Jan 31–Feb 2, 1994.

Address reprint requests to Dr Krasna, Division of Thoracic Surgery, University of Maryland Medical System, 22 S Greene St, Rm N4W87, Baltimore, MD 21201.

	References

Top Footnotes Abstract Introduction Material and Methods Results Comment Acknowledgments References

 

1. Orringer MB, Forastiere AA, Perez-Tamayo C, Urba S, Takasugi BJ, Bromberg J. Chemotherapy and radiation therapy before transhiatal esophagectomy for esophageal carcinoma. Ann Thorac Surg 1990;119:348–55.
2. Ellis FH Jr, Watkins E Jr, Krasna MJ, Heatley GJ, Balogh K. Staging of carcinoma of the esophagus and cardia: a comparison of different staging criteria. J Surg Oncol 1993;52:321–5.
3. Skinner DB, Little AG, Ferguson MK, et al. Selection of operation for esophageal cancer based on staging. Ann Thorac Surg 1986;204:391–401.
4. Krasna MJ, McLaughlin JS. Thoracoscopic lymph node staging for esophageal cancer. Ann Thorac Surg 1993;56:671–4.[Abstract]
5. Casson AG, Inculet RI, Zankowicz N, et al. Lymph node mapping for resectable carcinoma of the esophagus. Princeton, NJ: Bristol-Myers Squibb Co, 1992.
6. Krasna MJ, Flowers J, Attar S, McLaughlin JS. Combined thoracoscopic and laparoscopic lymph node staging of esophageal cancer [Abstract]. Presented at the 75th Annual Scientific Session of The American Association for Thoracic Surgery, Boston, MA, April 24–26, 1995.
7. Picus D, Balfe DM, Koehler RE, et al. Computed tomography in the staging of esophageal carcinoma. Radiology 1983;146:433–8.[Abstract/Free Full Text]
8. Whitteseey D. Prospective computed tomographic scanning in the staging of bronchogenic cancer. J Thorac Cardiovasc Surg 1988;95:876–82.[Abstract]
9. Pearson FG, Nelems JM, Henderson RD, Delarue NC. The role of mediastinoscopy in the selection of treatment for bronchial carcinoma with involvement of superior mediastinal lymph nodes. J Thorac Cardiovasc Surg 1972;64:382–90.[Medline]
10. Sennoke Y, Hiratsuka R, Doki K. Lymph node metastasis in cancer of the thoracic esophagus. Am J Surg 1981;141:216–8.[Medline]
11. Akiyama H, Tsurumaru M, Kawamura T, Ono Y. Principles of surgical treatment for carcinoma of the esophagus. Ann Surg 1981;194:438–46.[Medline]
12. Lefor AT, Merino MM, Steinberg SM, et al. Computerized tomographic prediction of extraluminal spread and prognostic implications of lesion width in esophageal carcinoma. Cancer 1988;62:1287–92.[Medline]
13. Markland CG, Manhari A, Davies P, et al. The role of computed tomography in assessing the operability of esophageal carcinoma. Eur J Cardiothorac Surg 1989;3:33–6.[Abstract]
14. Takashima S, Takeuchi N, Shiozaki H, et al. Carcinoma of the esophagus: CT vs MR imaging in determining resectability. AJR 1991;156:297–302.[Abstract/Free Full Text]
15. Lightdale CJ, Botet JF. Esophageal carcinoma: preoperative staging and evaluation of anastomotic recurrence. Gastrointest Endosc 1990:S11–6.
16. Dittler HJ, Rosch T, Lorenz R, et al. Failure of endoscopic ultrasonography to differentiate malignant from benign lymph nodes in esophagogastric cancer [Abstract]. Gastrointest Endosc 1992;38:240A.
17. Tio TL, Coene PPLO, Luiken GJHM, Tutgat GNJ. Endosonography in the clinical staging of esophagogastric carcinoma. Gastrointest Endosc 1990;36(Suppl):2–10.
18. Fok M, Cheng SWK, Wong J. Endosonography in patient selection for surgical treatment of esophageal carcinoma. World J Surg 1992;16:1098–103.[Medline]
19. Rice TW, Boyce GA, Sivall MV. Esophageal ultrasound and the preoperative staging of carcinoma of the esophagus. J Thorac Cardiovasc Surg 1991;101:536–43.[Abstract]
20. Murray GF, Wilcox BR, Starek PJK. The assessment of operability of esophageal carcinoma. Ann Thorac Surg 1977;23:393–9.[Abstract]
21. Dagnini G, Caldironi MW, Marin G, Buzzaccarini O, Tremolada C, Ruol A. Laparoscopy in abdominal staging of esophageal carcinoma. Gastrointest Endosc 1986;32:400–2.[Medline]

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This Article Abstract Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Mark J. Krasna Carolyn E. Reed Michael T. Jaklitsch David J. Sugarbaker Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Krasna, M. J. Articles by Sugarbaker, D. J. Search for Related Content PubMed PubMed Citation Articles by Krasna, M. J. Articles by Sugarbaker, D. J. Related Collections Related Article