HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Abstract Full Text (PDF) 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): Carolyn E. Reed Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Reed, C. E. Articles by Hawes, R. H. Search for Related Content PubMed PubMed Citation Articles by Reed, C. E. Articles by Hawes, R. H.

Ann Thorac Surg 1999;67:319-321
© 1999 The Society of Thoracic Surgeons

---

Original Articles

Esophageal cancer staging: improved accuracy by endoscopic ultrasound of celiac lymph nodes

^a Department of Surgery, Medical University of South Carolina, Charleston, South Carolina, USA
^b Division of Gastroenterology, Medical University of South Carolina, Charleston, South Carolina, USA

Address reprint requests to Dr Reed, Medical University of South Carolina, 171 Ashley Ave, Charleston, SC 29425
e-mail: reedce{at}musc.edu

Presented at the Forty-fifth Annual Meeting of the Southern Thoracic Surgical Association, Orlando, FL, Nov 12–14, 1998.

	Abstract

Top Abstract Introduction Patients and methods Results Comment References

 
Background. Clinical staging of esophageal cancer is required for optimal therapy but remains imprecise. Pathologic verification of involved lymph nodes could potentially direct treatment allocation. With the rising incidence of distal and gastroesophageal junction adenocarcinomas, assessment of the celiac axis lymph nodes (CLNs) becomes important because it is a common nodal drainage basin. Endoscopic ultrasound (EUS) permits evaluation of CLNs and biopsy by fine-needle aspiration. This study examined the usefulness of this staging tool.

Methods. A consecutive series of 62 patients with esophageal cancer considered resectable by computed tomographic scan underwent EUS for T and N staging and were retrospectively studied. A CLN visualized by EUS as greater than 5 mm was considered positive. Fine-needle aspiration of the CLN was performed routinely. Endoscopic ultrasound and computed tomographic staging were compared on the basis of pathologic verification of CLNs.

Results. It was possible to evaluate CLNs by EUS in 59 (95%) of 62 patients: positive in 19, negative in 40. In EUS-positive patients, fine-needle aspiration was positive in 15, falsely negative in 2, and not done in 2. By computed tomographic scan, CLNs were negative in 57 patients and positive in 2. The CLNs were positive in 23 of 54 patients eligible for CLN pathologic verification. All positive CLNs not identified by EUS (7 false-negative EUS) were microscopic foci in one or two nodes and were associated with T3 tumors. Sensitivity and specificity of EUS were 72% and 97%, respectively, compared with 8% and 100% for computed tomographic scan. When EUS identified CLNs, fine-needle aspiration confirmed positivity in 88% of cases.

Conclusions. Endoscopic ultrasound with fine-needle aspiration is useful in the detection and confirmation of CLN metastasis. In T3 tumors of the distal esophagus, a negative EUS result does not substantiate absence of CLN disease. Endoscopic ultrasound with fine-needle aspiration may be important in guiding treatment for patients with distal adenocarcinoma and documenting disease before neoadjuvant therapy.

	Introduction

Top Abstract Introduction Patients and methods Results Comment References

 
The staging of esophageal cancer remains imprecise. Computed tomography (CT) is useful for evaluating metastatic disease but does not allow accurate assessment of depth of tumor invasion or regional lymph node status. Endoscopic ultrasound (EUS) is presently the most accurate tool for estimating depth of tumor [1–3] and compared with CT has improved accuracy in the identification of metastatic regional lymph nodes [1–5]. However, histologic verification of involved lymph nodes is needed to clinically stage esophageal cancer more conclusively. Such ability would improve the design and interpretation of clinical trials and potentially help allocate patients to a particular treatment modality (ie, neoadjuvant therapy).

There is a rising prevalence of distal and gastroesophageal junction adenocarcinoma [6]. The celiac axis lymph nodes (CLNs) are considered by most surgeons to be a regional nodal basin of these tumors. Endoscopic ultrasound permits evaluation of CLNs and biopsy by fine-needle aspiration (FNA). The purpose of the present study was to evaluate the usefulness of this staging tool in potentially resectable tumors.

	Patients and methods

Top Abstract Introduction Patients and methods Results Comment References

 
Patients
Between January 1, 1994, and April 1, 1998, a consecutive series of 62 patients presenting with esophageal cancer and having no evidence of T4 or metastatic disease by CT scan were considered potential surgical candidates and underwent EUS staging at the Medical University of South Carolina. The status of the CLNs in this group was retrospectively reviewed.

Of the 62 patients, 51 were male and 11 female. Tumor location was midesophageal in 13 patients, distal esophageal in 35, gastroesophageal junction in 13, and diffuse in 1 (mid and distal esophagus). Histologic studies revealed adenocarcinoma in 38 patients, squamous cell in 22, adenosquamous in 1, and carcinosarcoma in 1.

Endoscopic ultrasound and fine-needle aspiration
Endoscopic ultrasound was performed, after informed consent was obtained, in an outpatient endoscopy suite using topical oropharyngeal anesthesia and intravenous sedation (midazolam and meperidine). All EUS examinations were initially performed at 7.5- and 12-MHz frequencies using a radial scanning echoendoscope (Olympus GIF-UM 20; Olympus American Inc, Lake Success, NY). Dilation was performed up to 42F to 45F to allow passage of the 13-mm echoendoscope using wire-guided Savary-Gilliard dilators (Wilson-Cook Medical, Inc, Winston-Salem, NC). An attempt to visualize the celiac axis was made in all cases by positioning the echoendoscope in the proximal stomach. In normal subjects, EUS does not detect CLNs. In the present study, a node greater than 5 mm was considered positive. Peritumoral nodes that were greater than 10 mm in the short-axis diameter, round and hypoechoic, and having sharp borders were recorded as abnormal. Fine-needle aspiration biopsy of CLNs was performed using either a mechanical sector scanning biopsy echoendoscope (Olympus GF UM 30P; Olympus America Inc) or a linear array sector scanning echoendoscope (FG 32-UA; Pentax, Orangeburg, NY).

The instrument was placed in the stomach lumen opposite the identified CLN. The FNA needle–sheath system, consisting of a 23- or 24-gauge needle (Wilson-Cook, Olympus America Inc or Pentax) was inserted through the working channel of the endoscope. The needle was advanced from the metal sheath through the wall of EUS normal mucosa of the stomach and guided into the target site using real-time ultrasound. The stylet was removed, and suction was applied with a 10-mL syringe while the needle was manipulated back and forth within the lymph node. After 1 minute, the suction was released, and the needle was retracted. The aspirate was placed on glass slides, preserved with Diff-Quik stain (American Scientific Products, McGraw Park, IL), and reviewed immediately by an on-site pathologist to ensure adequate specimen (ie, lymphocytes). At least three adequate samples were obtained.

Pathologic verification
Histologic or cytologic examinations of the CLNs was possible in all evaluable cases but 1 by FNA, surgical resection, or laparoscopy (1 patient). Progressive disease occurred in 1 patient, which was verified by cervical exploration, and no laparotomy was performed. At the time of operation, CLNs (lymph nodes at the base of the celiac axis and the proximal left gastric artery) were dissected en bloc with the specimen and labeled by the surgeon (C.R.). When small, the entire lymph node was submitted. Larger lymph nodes were bisected and the two portions examined.

Analysis
The sensitivity and specificity of EUS for staging CLNs were calculated on the basis of pathologic verification and compared with CT scanning results. The negative and positive predictive values were assessed for EUS evaluation of CLNs.

	Results

Top Abstract Introduction Patients and methods Results Comment References

 
It was possible to evaluate CLNs by EUS in 59 (95%) of the 62 patients. In 3 patients, the obstructing tumors could not be dilated, and a catheter miniprobe (Olympus UM2R/3R, Olympus American Inc) was used to assess the proximal portion of the lesions. In the 59 remaining patients, CLNs were considered positive by EUS in 19 patients and negative in 40. In the EUS-positive patients, FNA was positive in 15 patients, falsely negative in 2, and not done in 2. There was no morbidity when FNA was added to EUS. By CT scan, CLNs were negative in 57 patients and positive in 2.

The CLNs were found to be positive in 26 of 57 patients eligible for CLN evaluation. One patient did not undergo laparotomy secondary to progressive disease found at initial cervical exploration. In another patient, primary tumor directly invaded the celiac axis, and separate assessment of the nodes was not possible. Of the 26 patients with positive CLNs, 7 were not identified by EUS. These 7 patients had microscopic foci of tumor in one or two celiac nodes (approximately 15% of all detected CLNs), and all these patients had T3 tumors. No false-negative EUS findings occurred in patients with T1 or T2 tumors.

Thirty-three patients underwent preoperative adjuvant therapy, with most receiving two cycles of 5-fluorouracil and cisplatin combined with concurrent radiotherapy. Three patients were EUS positive for involvement of CLNs and were found to have N0 disease at resection. Squamous cell carcinoma considered potentially resectable in 4 patients was declared unresectable after FNA of CLNs was positive (M1 disease). They were treated with chemoradiation or radiation. Three other patients who had FNA-positive CLNs chose to be treated by chemoradiotherapy alone.

The calculated sensitivity and specificity of EUS in the 57 patients with pathologic verification of CLNs was 72% and 97%, respectively. The CT sensitivity was 8% and specificity 100%. The positive predictive value of EUS was 95%, and the negative predictive value was 82%. When EUS identified CLNs, FNA confirmed positivity in 88% of cases.

	Comment

Top Abstract Introduction Patients and methods Results Comment References

 
The staging of cancer allows the physician to recommend treatment, anticipate the prognosis, and communicate and study the results of various treatment options. The staging of esophageal cancer has lacked precision in the identification of the T and N components. Computed tomography, the most frequently used staging tool, is helpful in evaluating adjacent organ involvement (T4 disease) and metastases, but is inaccurate in the assessment of nodal disease and depth of tumor invasion. Endoscopic ultrasound is presently the most accurate noninvasive method for staging the T and N components [1–5]. The ability to combine FNA with EUS potentially offers greater precision in staging by histologic verification of identified lymph nodes. Although not yet as refined, but in a manner similar to the mediastinoscopic evaluation of non–small cell lung cancer to confirm stage IIIA disease, this procedure could then aid in the allocation of treatment and the interpretation of the results of clinical trials.

At present, EUS with FNA of peritumoral lymph nodes cannot be performed because the needle would pass through the tumor in the esophageal wall. Abnormal periesophageal nodes distal or proximal to the tumor can be sampled. The CLNs are readily accessible for EUS-guided FNA. With the rising incidence of distal adenocarcinoma, CLNs become an important site of metastatic drainage. As in the case at many centers, we considered distal adenocarcinomas with CLN involvement to be locally advanced (ie, N1 disease) and still potential candidates for resection. The usefulness of the evaluation of CLNs by EUS and biopsy by FNA was assessed in a group of patients being considered for operation.

In the present series, the sensitivity of EUS for identification of positive CLNs was 72%, with a negative predictive value of 82%. As expected, CT was extremely poor in staging CLNs. It is doubtful that the sensitivity of EUS will ever be greater than 70% to 75% because microscopic foci of metastatic disease in normal lymph nodes (< 5 mm) will be missed. However, when CLNs are detected by EUS, FNA is highly successful in confirming metastasis.

To increase the yield of identifying positive CLNs before treatment, laparoscopic evaluation has been proposed. Both Luketich and associates [7] and Krasna and colleagues [8] have used thoracoscopic and laparoscopic staging to assess lymph nodes. Laparoscopy accurately identified the disease status of CLNs in 16 of 17 patients described by Krasna and associates [8]. Luketich and colleagues [7] compared EUS with minimally invasive operation in 26 patients. Endoscopic ultrasound was considered positive for N1 disease in 12 of 21 patients, whereas laparoscopy and thoracoscopy revealed N1 disease in 18 of these 21 patients. However, only a linear array echoendoscope was used in the Luketich study. Most centers stage with a radial scanner, which permits complete visualization in a 360-degree field. With the requirement of general anesthesia, an operative time often exceeding 3 hours, and the need for a 2- to 3-day hospital stay, laparoscopic and thoracoscopic staging are actually invasive staging tools. Luketich and colleagues [7] estimated total average charges at $20,000 to $25,000 for such staging. At our institution, EUS with FNA adds approximately 30 minutes to routine outpatient esophagoscopy, and total charges average $1,000.

Positron emission tomography is the newest staging modality, and its usefulness in esophageal cancer is undefined. At present, it is most useful in detecting distant metastatic disease. Peritumoral lymph nodes cannot easily be distinguished from the tumor. Celiac lymph nodes less than 10 mm in diameter containing metastatic tumor would fall below the sensitivity of positron emission tomography [9, 10].

Rice and associates [11] have shown that for patients with esophageal carcinoma, T status is an important predictor of N disease. The likelihood of N1 disease was 77% for 219 patients with T3 disease. In our series, the 7 patients who had false-negative EUS assessment of CLNs had T3 tumors. One could argue that this select group might benefit from laparoscopic assessment. However, 4 of these patients had peritumoral lymph nodes that were classified as positive. With the anticipated development of a sheathed aspiration needle, the need for more aggressive staging would be limited to very few patients.

Ultimately, the usefulness of a staging tool will depend on its ability to affect treatment decisions. The best treatment for T3 or N1 disease, or both, remains controversial and requires further study. Pathologic verification of N1 disease has the potential of providing baseline information against which effectiveness of treatment can be measured.

In conclusion, EUS with FNA is useful in the detection and confirmation of CLN metastasis. In T3 tumors of the distal esophagus, negative EUS results do not substantiate absence of CLN disease. Endoscopic ultrasound with FNA may prove to be critically important in guiding treatment of patients with distal adenocarcinomas and in documenting involved CLNs before preoperative neoadjuvant therapy.

	References

Top Abstract Introduction Patients and methods Results Comment References

 

1. Ziegler K., Sanft C., Zeitz M., et al. Evaluation of endosonography in TN staging of oesophageal cancer. Gut 1991;32:16-20.[Abstract/Free Full Text]
2. Botet J.F., Lightdale C.J., Zauber A.G., et al. Preoperative staging of esophageal cancer: Comparison of endoscopic US and dynamic CT. Radiology 1991;181:419-425.[Abstract/Free Full Text]
3. Tio T.L., Coene P.P.L.O., Schouwink M.H., Tytgat G.N.J. Esophagogastric carcinoma: preoperative TNM classification with endosonography. Radiology 1989;173:411-417.[Abstract/Free Full Text]
4. Grimm H., Soehendra N., Hamper K., et al. Endosonography versus computed tomography for determination of loco-regional spread in esophageal cancer: a prospective controlled study. In: Ferguson M.K., Little A.G., Skinner D.B., eds. Diseases of the esophagus, vol 1: Malignant diseases. Armonk, NY: Futura, 1990:125-134.
5. Vilgrain V., Mompoint D., Palazzo L., et al. Staging of esophageal carcinoma: comparison of results with endoscopic sonography and CT. AJR Am J Roentgenol 1990;155:277-281.[Abstract/Free Full Text]
6. Blot W.J., Devesa S.S., Kneller R.W., Fraumeni J.F. Rising incidence of adenocarcinoma of the esophagus and gastric cardia. JAMA 1991;265:1287-1291.[Abstract]
7. Luketich J.D., Schauer P., Landreneau R., et al. Minimally invasive surgical staging is superior to endoscopic ultrasound in detecting lymph node metastases in esophageal cancer. J Thorac Cardiovasc Surg 1997;114:817-823.[Abstract/Free Full Text]
8. Krasna M.J., Flowers J.L., Attar S., McLaughlin J. Combined thoracoscopic/laparoscopic staging of esophageal cancer. J Thorac Cardiovasc Surg 1996;111:800-807.[Abstract/Free Full Text]
9. Block M.I., Patterson G.A., Sundaresan R.S., et al. Improvement in staging of esophageal cancer with the addition of positron emission tomography. Ann Thorac Surg 1997;64:770-777.[Abstract/Free Full Text]
10. Luketich J.D., Schauer P.R., Meltzer C.C., et al. Role of positron emission tomography in staging esophageal cancer. Ann Thorac Surg 1997;64:765-769.[Abstract/Free Full Text]
11. Rice T.W., Zuccaro G., Adelstein D.J., Rybicki L.A., Blackstone E.H., Goldblum J.R. Esophageal carcinoma: depth of tumor invasion is predictive of regional lymph node status. Ann Thorac Surg 1998;65:787-792.[Abstract/Free Full Text]

This article has been cited by other articles:

				P. Singh, B. Camazine, Y. Jadhav, R. Gupta, P. Mukhopadhyay, A. Khan, R. Reddy, Q. Zheng, D. D. Smith, R. Khode, et al. Endoscopic Ultrasound As a First Test for Diagnosis and Staging of Lung Cancer: A Prospective Study Am. J. Respir. Crit. Care Med., February 15, 2007; 175(4): 345 - 354. [Abstract] [Full Text] [PDF]

				C. J. Lightdale and K. G. Kulkarni Role of Endoscopic Ultrasonography in the Staging and Follow-Up of Esophageal Cancer J. Clin. Oncol., July 10, 2005; 23(20): 4483 - 4489. [Abstract] [Full Text] [PDF]

				H.L. van Westreenen, M. Westerterp, P.M.M. Bossuyt, J. Pruim, G.W. Sloof, J.J.B. van Lanschot, H. Groen, and J.Th.M. Plukker Systematic Review of the Staging Performance of 18F-Fluorodeoxyglucose Positron Emission Tomography in Esophageal Cancer J. Clin. Oncol., September 15, 2004; 22(18): 3805 - 3812. [Abstract] [Full Text] [PDF]

				M. Koshy, N. Esiashvilli, J. C. Landry, C. R. Thomas Jr., and R. H. Matthews Multiple Management Modalities in Esophageal Cancer: Epidemiology, Presentation and Progression, Work-up, and Surgical Approaches Oncologist, April 1, 2004; 9(2): 137 - 146. [Abstract] [Full Text] [PDF]

				C. E. Reed General thoracic surgery and the Southern Thoracic Surgical Association: the second 25 years Ann. Thorac. Surg., November 1, 2003; 76(90050): S14 - 16. [Full Text] [PDF]

				D. K. Dhar, M. Tachibana, N. Kinukawa, M. Riruke, H. Kohno, A. G. Little, and N. Nagasue The Prognostic Significance of Lymph Node Size in Patients With Squamous Esophageal Cancer Ann. Surg. Oncol., December 1, 2002; 9(10): 1010 - 1016. [Abstract] [Full Text] [PDF]

				M. B. Wallace, P. J. Nietert, C. Earle, M. J. Krasna, R. H. Hawes, B. J. Hoffman, and C. E. Reed An analysis of multiple staging management strategies for carcinoma of the esophagus: computed tomography, endoscopic ultrasound, positron emission tomography, and thoracoscopy/laparoscopy Ann. Thorac. Surg., October 1, 2002; 74(4): 1026 - 1032. [Abstract] [Full Text] [PDF]

				M. J. Krasna, X. Jiao, J. R. Sonett, Z. Gamliel, A. Eslami, Y. Raefaly, and Y. Mao Thoracoscopic and laparoscopic lymph node staging in esophageal cancer: do clinicopathological factors affect the outcome? Ann. Thorac. Surg., June 1, 2002; 73(6): 1710 - 1713. [Abstract] [Full Text] [PDF]

				K. S. Parmar, J. B. Zwischenberger, A. L. Reeves, and I. Waxman Clinical impact of endoscopic ultrasound-guided fine needle aspiration of celiac axis lymph nodes (M1a disease) in esophageal cancer Ann. Thorac. Surg., March 1, 2002; 73(3): 916 - 920. [Abstract] [Full Text] [PDF]

				M. A. Eloubeidi, M. B. Wallace, B. J. Hoffman, M. B. Leveen, A. Van Velse, R. H. Hawes, and C. E. Reed Predictors of survival for esophageal cancer patients with and without celiac axis lymphadenopathy: impact of staging endosonography Ann. Thorac. Surg., July 1, 2001; 72(1): 212 - 219. [Abstract] [Full Text] [PDF]

				H. Igaki, H. Kato, Y. Tachimori, H. Sato, H. Daiko, and Y. Nakanishi Prognostic evaluation for squamous cell carcinomas of the lower thoracic esophagus treated with three-field lymph node dissection Eur. J. Cardiothorac. Surg., June 1, 2001; 19(6): 887 - 893. [Abstract] [Full Text] [PDF]

				T. Nishimaki, O. Tanaka, N. Ando, H. Ide, H. Watanabe, M. Shinoda, W. Takiyama, H. Yamana, K. Ishida, K. Isono, et al. Evaluation of the accuracy of preoperative staging in thoracic esophageal cancer Ann. Thorac. Surg., December 1, 1999; 68(6): 2059 - 2064. [Abstract] [Full Text] [PDF]

This Article Abstract Full Text (PDF) 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): Carolyn E. Reed Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Reed, C. E. Articles by Hawes, R. H. Search for Related Content PubMed PubMed Citation Articles by Reed, C. E. Articles by Hawes, R. H.