Ann Thorac Surg 2007;83:1265-1272
© 2007 The Society of Thoracic Surgeons
Original Articles: General Thoracic
Appraisal of a Revised Lymph Node Classification System for Esophageal Squamous Cell Cancer
Dipok Kumar Dhar, PhDa,b,*,
Shinji Hattori, MDb,
Yasuhito Tonomoto, MDb,
Tadakazu Shimoda, PhDc,
Hoichi Kato, PhDd,
Mitsuo Tachibana, PhDb,
Kosho Matsuura, MDa,
Yojiro Mitsumoto, PhDa,
Alex G. Little, MDe,
Naofumi Nagasue, PhDb
a Naze Tokushukai Hospital, Amamioshima, Kagoshima, Japan
b Department of Digestive and General Surgery, Faculty of Medicine, Shimane University, Japan
c Department of Pathology, National Cancer Center, Tokyo, Japan
d Department of Surgery, National Cancer Center, Tokyo, Japan
e Department of Surgery, Wright State University, Dayton, Ohio
Accepted for publication December 4, 2006.
* Address correspondence to Dr Dhar, The UCL Institute of Hepatology, RF &UCL Medical School, 69–75 Chenies Mews, London WC1E 6HX, UK (Email: reghdkd{at}ucl.ac.uk).
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Abstract
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Background: Node-positive patients with esophageal carcinoma constitute a heterogeneous population with a variable prognosis, which the current staging system insufficiently addresses. To that end, 863 patients with a curative resection for esophageal squamous cell carcinoma were analyzed to evaluate a useful and simple nodal classification system.
Methods: Along with standard conventional clinicopathologic factors, data for metastatic lymph node (MLN) number, metastatic to examined LN ratio (MLN ratio), and MLN size were evaluated. The greatest microscopic dimension of the metastatic tumor inside the largest MLN (MLN size) was measured on histopathologic slides. Patients with MLNs were classified into n1 (<9 mm) and n2 (
9mm) groups, according to size of MLNs (n-stage).
Results: The paratracheal LNs most frequently contained the largest MLN and among them the right recurrent laryngeal LNs were the most common site (81.8%). Patients were stratified into significant groups by all the nodal criteria. In multivariable analysis, MLN size n-stage and MLN ratio N-stage were the best independent predictors for disease-free and overall survival, respectively. In the disease-free survival, MLN ratio N-stage subcategories were divided into prognostic groups according to the n-stage. A combined nodal staging strategy combining the n-stage and N-stage had the strongest prognostic value and was used for the tumor-node-metastasis classification with distinct separation of patients into prognostic groups.
Conclusions: Results of this study indicate that the MLN size may serve as an accurate metric to classify node-positive patients and a combination of the MLN ratio and size may have synergism in classifying node-positive patients into prognostically homogenous groups.
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Introduction
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Despite an aggressive therapeutic strategy, the overall outcome of patients with esophageal carcinoma has not improved much because of either a lack of efficacy of the currently employed therapeutic options or the targeting of these therapies to inaccurately or insufficiently staged patients [1, 2]. Standardized tumor staging facilitates the comparison of treatment results from different institutions and should correlate with patient prognosis. The Union International Contra la Cancrum (International Union Against Cancer) tumor (T), node (N), and metastasis (M) (UICC/TNM) system of classification is widely used by the clinicians to stratify patients into prognostic groups and select treatment strategies. With increased sophistication in cancer diagnosis and improvement in the understanding of cancer biology, amendments to this system over time are advocated [3]. Historically, esophageal cancer staging systems are less than ideal. The T category of the TNM classification has been improved by using the depth of wall penetration instead of tumor length; however, N staging remains imperfect.
Patients with lymph node positive cancer comprise a heterogenous population with variable prognostic outcomes and need to be prognostically stratified to optimize the treatment regimen [4]. In the literature, multiple criteria have been suggested to classify the node-positive patients, including the level of nodal involvement, number of metastatic lymph nodes (MLNs), ratio between number of dissected, and number of MLNs (MLN ratio), and presence or absence of extranodal spreading [5–13].
Previously, in a smaller number of patients, we reported that the greatest dimension of the largest MLN, as measured on hematoxylin and eosin-stained (H&E) histopathologic specimens, stratifies node-positive patients into prognostically homogeneous groups in most gastrointestinal cancers, including esophageal squamous cell cancer [14–16]. A similar notion for classification of node-positive patients with esophageal cancer has been advocated in other studies [17–19]. Fok and colleagues [20] observed that surgeons could distinguish small from grossly enlarged MLNs at operation and this could supplement the shortcomings of the present TNM classification. In this study, we measured the microscopic diameter of the tumor deposit in the largest MLN in a prospective database of a large number of patients with esophageal cancer treated in a single center. The goal was to determine if this lymph node assessment criterion, either alone or in combination with the above identified other criteria, would enhance current nodal staging strategies.
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Patients and Methods
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Between 1983 and 2003, a total of 1,888 patients underwent esophageal resection for esophageal carcinoma at the National Cancer Center, Tokyo, Japan. The 863 who underwent a curative resection, had a complete follow-up, and were without any preoperative therapy were included in this study. Four hundred twenty-four (49%) patients were without any MLN and 439 (51%) patients had metastasis in the resected LNs. The patient study group consisted of 744 (86%) men and 119 (14%) women, aged between 35 and 88 years (mean, 62.6; median, 62). The ethical committee of the National Cancer Center, Tokyo, Japan approved the study protocol. As this is a retrospective study, individual consent from patients was waived.
All patients underwent a standardized esophagectomy through a right thoracotomy and gastrointestinal continuity was restored mostly by a gastric and occasionally by a colonic interposition, as described previously [21]. Patients with cervical nodal involvement as detected by preoperative computed tomographic examination always underwent a three-field LN dissection including the cervical, thoracic, and abdominal basins. The rest of the patients had a two-field LN dissection until March 2000 and after that period a three-field LN dissection became a routine procedure for all patients with esophageal carcinoma in our institution. The LNs removed en bloc with the tumor specimen were harvested by the pathologists at the Central Pathological Department. Individual groups of lymph nodes dissected separately at operation were aliquoted in formalin and submitted to the pathological department. All lymph nodes were cut at several levels along the long axis, embedded in paraffin, and sectioned for H&E staining. Pathologists examined all slides and determined the metastatic status of dissected lymph nodes. The mean number of lymph nodes removed per patient at operation was 53.7 (range, 4 to 125; median, 53).
Hematoxylin and eosin stained archival lymph node sections were retrieved from the tissue bank and were used for the determination of the MLN size. The actual size of the metastatic tumor at its greatest dimension (in millimeters) inside the largest MLN was considered as the MLN size. The MLN number was the number of LNs with metastatic deposits and the MLN ratio was determined by dividing the total number of MLNs by the total number of harvested LNs in each patient. All MLNs were evaluated under a light microscope by two individual investigators with no knowledge of patient outcome. We used a standard microscope incorporating a calibrated measure in one of its eyepieces. In order to determine the microscopic size of the metastatic deposit at its largest diameter, we screened all the MLNs in a patient at low magnifications (x2 or x4) and selected the largest MLN for the measurement. The actual measurement was done at a higher magnification (x4 or x10) and a correction for the magnification was done before getting the final measurement. When more than one distinct metastatic deposit was present, the sum of all metastatic deposits was considered as the MLN size.
Tumors were classified using the pTNM category according to the UICC/American Joint Committee on Cancer [AJCC] 2002 classification. Eighty-one (18%) patients received chemotherapy, radiotherapy, or both in the postoperative period. Among the node-positive patients, a two-field lymph node dissection was executed in 160 (36.4%) and a three-field lymph node dissection was performed in 279 (63.6%). A prospective database was maintained for patients with esophageal carcinoma and the last follow-up was done in March 2005.
Statistical Analysis
Correlation between size of MLNs and number of MLNs was done by the Spearman rank correlation test. Kaplan-Meier estimates of survival for recurrence-free and overall survival were determined. Differences in survival were assessed with a log-rank test. Independent variables predicting survival were evaluated with the Cox proportional hazards model, incorporating all variables found to be significant in the univariate analysis. The Statview 4.5J (Abacus Concepts, Berkley, CA) was used for data analysis.
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Results
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The total number of LNs and the number of MLNs excised per patient varied from 4 to 125 (mean, 53.7; median, 53) and 1 to 55 (mean, 4.2; median, 3), respectively. The MLN ratio varied from 0.01 to 1 (median, 0.05). The greatest microscopic dimension of metastatic tumor inside the largest MLN varied from 0.10 mm to 36 mm (mean, 10.1; median, 9 mm). After serial bisection at different cutoff points and two-sample log-rank test, the statistical power for prediction of patient survival decreased above the 8-mm cutoff value. Therefore, patients with MLNs were divided into two prognostic groups; n1 (MLNs < 9 mm, n = 216) and n2 (MLNs 9 mm, n = 223) (n stage). In addition, widely used standards for MLN number (3 or less and 4 or more, number N-stage) and MLN ratio (cutoff level <10% and >10%, MLN ratio N-stage) were used to stratify patients into prognostic groups. According to the number criterion, 269 patients had N1 disease and 170 patients had N2 disease in the MLN number N-stage. By the MLN ratio N-stage criterion, 307 were classified as having N1 disease and 132 had N2 disease. There was a significant direct correlation between the MLN size and both the number and ratio of MLNs (Spearman rank test, MLN number, p < 0.0001 and r2 = 46.8, and MLN ratio, p < 0.0001, and r2 = 35.6).
Location of the Largest MLN
Distribution of the largest MLN location in relation to the site of the primary tumor is shown in Figure 1. The regional LNs were numbered according to the Japanese classification [22]. The thoracic paratracheal LNs (No. 106) (64%), upper thoracic paraesophageal LNs (No. 105) (7%), and supraclavicular LNs (No. 104) (7%) were the most frequently involved sites when the tumor was located in the upper thoracic esophagus. The thoracic paratracheal LNs (31%) and right cardiac LNs (No.1) (14%) were most frequently involved when the tumor was located in the middle part of the esophagus. The right (No. 1) (28%) and left (No. 2) (16%) cardiac and thoracic paratracheal LNs (No. 106) (15%) were most commonly involved when the tumor was present in the lower thoracic esophagus. Considering all primary tumor locations, the paratracheal LNs (No. 106) were the most frequently involved and among them the right recurrent laryngeal LNs were the most frequently (81.8%) involved.
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Fig 1. Distribution percentages of the largest metastatic lymph node location in relation to the site of the primary tumor: (A) upper, (B) middle, and (C) lower part of the thoracic esophagus. Lymph node locations are numbered according to the Japanese classification [22].
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Survival Analysis
At last follow-up (range, 14 to 275 months; median, 91 months), a total of 234 (27%) of 863 patients had disease recurrence. When stratified according to our n-stage, there were significant differences in overall (OS) (p = 0.0006, log-rank test) and disease-free (DFS) (p < 0.0001, log-rank test) survival between patients with n1 and n2 disease (Fig 2A). Similarly, both the number and ratio (Fig 2B) of MLNs had significant impact on both OS (p < 0.0001, log-rank test) and DFS (p < 0.0001, log-rank test). Because of a better predictability of patient survival by the MLN ratio N-stage than the MLN number N-stage, in subgroup analyses, the MLN ratio N-stage was used. Subgroup analyses (Fig 3) showed that patients with both MLN ratio N1 and N2 disease could be further stratified in respect to the DFS by our n-stage (N1: DFS, p < 0.0003 and OS, p = 0.1419; N2: DFS, p = 0.0002 and OS, p = 0.1472). When the new n groups were split according to the MLN ratio N-stage, only patients belonging to the n2 group were significantly separated into prognostic groups (n1: DFS, p = 0.0528 and OS, p = 0.0022; n2: DFS, p < 0.0001 and OS, p < 0.0001).
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Fig 2. Disease-free survival according to our n-stage (A) and metastatic lymph node (MLN) ratio N-stage (B) are shown.
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Fig 3. Kaplan-Meier disease-free survival of patients when metastatic lymph node (MLN) size n-stage groups (A, B) and MLN ratio N-stage groups (C, D) were further stratified by the MLN size n-stage and MLN ratio N-stage, respectively.
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Multivariable Analysis
The following parameters were significant predictors of survival in the univariate analysis and were included in the multivariable analysis: age, operation time, intraoperative blood loss, venous and lymphatic invasion, tumor size, T-stage, extent of LN dissection, new n-stage, MLN number N-stage, and MLN ratio N-stage. For DFS, the new n-stage (hazard risk [HR] 2.24, p < 0.0001) was the strongest independent predictor. Other cofactors retaining independent predictability were venous invasion (HR1.85, p = 0.0006), T-stage (HR1.68, p = 0.0099), and operation time (HR 0.869, p = 0.0184) (Table 1). In the OS, patient’s age (HR1.29, p = 0.0002), venous invasion (HR1.42, p = 0.0147), and MLN ratio N-stage (HR1.66, p = 0.0073) became independent predictors (data not shown).
A combination of the new n-stage and MLN ratio N-stage was used to construct a combined N-stage where patients with both n1 and N1 disease were considered to have N1 disease, patients with both n2 and N2 diseases as N3, and all others were grouped under the N2 stage. This combined N-stage system had significant impact on both DFS and OS (Fig 4A). When incorporated in the multivariable analysis, the combined N-stage became the strongest independent predictor in both the DFS (p < 0.0001) and OS (p = 0.0030) (data not shown).
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Fig 4. Disease-free survival curves according to the combined N-stage (A) (MLN ratio N-stage + MLN size n-stage) and (B) TNM stage incorporating the combined N-stage. In combined N-stage, patients with both n1 (MLN size n-stage) and N1 (MLN ratio N-stage) disease were considered to have N1 disease, patients with both n2 and N2 diseases as N3, and all others were grouped under the N2 stage. (MLN = metastatic lymph node; TNM = tumor node metastasis.)
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TNM Classification
Patients were stratified into four prognostic groups according to the T-stage, combined N-stage, and M-stage (distant visceral metastasis) as follows: stage I, T1/T2N0MO; stage II, T3N0M0, T1/T2N1M0; stage III, T4N0M0, T3N1M0, T1/T2N2M0; and stage IV, T4N1/N2M0, T3N2M0, any T N3, M1. As shown in Figure 4B, this approach stratified patients into prognostically homogenous groups and the 5-year DFS and OS for stage I, II, III, and IV were 80% and 67%, 65% and 55%, 34% and 47%, and 7.5% and 27%, respectively (DFS, p < 0.0001, HR, N1 vs N2, 1.99 and N2 vs N3 3.72; and OS, p < 0.0001, HR, N1 vs N2, 1.18 and N2 vs N3 1.98). Patients with UICC/TNM (2002) stage were reclassified according to the new TNM classification, which showed that those with stages IIb, III, and IV were heterogenous in respect to prognosis and could be further separated by the new classification (Table 2).
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Table 2 Stratification of Union International Contra la Cancrum (UICC) Tumor Node Metastasis (TNM) Stages According to the New TNM Staging, and Survival Differences Between the New Subgroups
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Comment
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Staging patients with esophageal carcinoma remains a clinician’s challenge. In the era of multidisciplinary approaches to treat cancers, optimum staging to obtain precision in identification of severity of the disease is necessary to tailor treatment appropriately and for documentation of disease for exchange of information. Currently, stage classification of esophageal carcinoma falls short of meeting some of these goals [3, 4]. In this study we have shown that adoption of a simple criterion may contribute to these goals.
Several studies have recommended the number of MLNs as a useful criterion to classify node-positive patients [5]. However, a lack of consensus on the cutoff point (varies from 1 to 8) and a strong dependency of predictability on the number of resected nodes indicate that this criterion could be further refined. To overcome this shortcoming, a ratio-based (involved to dissected LNs) classification has been advocated [23, 24]. In esophageal cancer, results of several carefully done studies indicate that the ratio-based classification serves better than the number based classification [8, 9, 11, 25]. In our study, both the MLN number and MLN ratio were significant prognostic factors; however, the MLN ratio N-stage had a stronger prognostic impact than the MLN number N-stage. As far as DFS, both subgroups of the MLN ratio N-stage could be separated into prognostic groups by the MLN size n-stage, whereas only the n2 group of the n-stage could be split into prognostic groups by the MLN ratio N-stage (Fig 3). A multivariable prognostic analysis shows that among the several clinicopathologic factors MLN size n-stage is the strongest independent prognosticator for DFS. Similarly, two other groups reported that the area of metastatic tumor inside LNs, as assessed by using an image grabbing analysis technique, was an independent prognostic indicator for esophageal cancer [18, 19].
Metastatic involvement of regional LNs and the extent of involvement may serve as the barometer of the malignant potential of the primary tumor as well as the competency of the host immune response. The number of involved MLNs and the maximum size of the tumor inside a MLN may represent the vertical and horizontal axes of the metastatic profile of a primary tumor, respectively. It seems that the ratio-based classification has a trend to understage some of the patients, whereas the size-based classification may upstage. From this perspective, it seems worth taking into consideration both criteria for the purpose of formulation of an optimum stage classification. As expected, this new paradigm has the strongest predictability for both the DFS and OS in the multivariable analysis (data not shown). When incorporated in the TNM classification, this approach distinctly stratified patients into four prognostic groups with a 5-year DFS of 80%, 65%, 34%, and 7.5% for patients with stages I, II, III, and IV, respectively.
The LN size-based classification has several advantages over number-based classification [14–16]. It is a very simple and objective method to classify node-positive patients and is applicable at any hospital having a microscope. Accumulated evidence shows that an extended lymphadenectomy in experienced hands improves tumor clearance and produces a beneficial effect on patient prognosis [26, 27]. However, because of increased morbidity and mortality rate, lymphadenectomy is often restricted to the periesophageal region. As shown in Figure 1, most of the largest MLNs are located in the immediate vicinity of the primary tumor and could easily be dissected at operation and thus a complete staging could be achieved with the n-stage approach. Results of this study show that particular attention should be paid to the paratracheal and cardiac LNS because they most frequently harbor the largest MLN. Among the patients who underwent a three-field LN dissection, the cervical LN involvement was more than three times higher when the paratracheal or abdominal MLNs were 9 mm or greater in size (53 of 157) than those with MLNs less than 9 mm in size (13 of 122) (p = 0.0001, 
2 test data not shown). Therefore, patients with a MLN in the thoracic or abdominal echelon of 9 mm or greater in size may benefit from a cervical LN dissection.
The UICC N-stage in gastric carcinoma is based on the number of MLNs; however, patients with metastasis in the nonregional LNs (metastasis in retropancreatic, mesenteric, and paraaortic LNs) cannot be classified with this criterion, which makes the classification more complicated. Also in esophageal cancer, the nonregional MLNs are classified as distant metastatic disease (M1); however, the prognosis of this group of patients is not always dismal [28, 29]. In our previous studies, we showed that our classification scheme has a unique ability to predict prognosis without separating nodes into regional and nonregional compartments [14, 15]. Accurate preclinical staging helps in decision making regarding the appropriate treatment option, whereas intraoperative assessment of the extent of the LN involvement helps in optimization of extent of dissection. With the advent of sophisticated investigative techniques such as positron emission tomography, MLN size could be identified with high precision and may help in designing appropriate treatment. Luketich and colleagues [30] described that when the MLN size is 1 cm or greater then the MLNs could be diagnosed with 100% accuracy by using a positron emission tomography scan. The disadvantage of the size-based classification lies with the upstaging effect in a certain number of patients. In our previous studies, we measured the size of the largest MLN itself rather than the actual size of the metastatic deposit inside the MLN and found that reactively enlarged MLNs with tiny metastatic deposits caused upstaging effect. In this study, we found that the actual size of metastatic deposit had a superior predictability of prognosis than the macroscopic size of the largest MLN (p < 0.0001 vs p = 0.0011, respectively, data not shown) and the actual size of the metastatic tumor deposit was considered as MLN size. Still, during measuring the size of the metastatic tumor, we encountered an upstaging effect of the criterion due to the presence of scattered hemorrhagic, cystic, and necrotic spots inside a MLN, which may compromise an accurate measurement of the tumor deposits. Therefore, a more precise classification might be achieved if a second largest MLN with homogenous metastatic deposit is selected when these erroneously enlarged nodes are found.
In conclusion, results of this large series of patients reinforce our previous observation that the greatest dimension of the largest MLN serves as an efficient metric to classify the node-positive patients with esophageal carcinoma. In synergy with the MLN ratio N-stage, this new n-stage further increases the predictability of patient prognosis and supplements the UICC/TNM stage classification. This unique classification system may be applicable after either an extended or limited resection and without separating the MLNs into regional and nonregional categories. However, these crude methods of classification alone may not satisfactorily reflect the biological aggressiveness of the tumor and should eventually be supplemented by more sophisticated molecular markers such as expression status of the epidermal growth factor receptor or vascular endothelial growth factor receptor. Until these sophisticated molecular biological techniques are available for general use, this new classification addresses the present need for a useful classification system for node-positive patients with esophageal carcinoma.
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Acknowledgments
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The authors are grateful to Ms S. Sekine, Department of Pathology, National Cancer Center, Tokyo and Mrs M. Nada, Department of Digestive and General Surgery, Shimane University for their technical assistance for this work.
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References
|
|---|
- Parkin DM. Global cancer statistics in the year 2000 Lancet Oncol 2001;2:533-543.[Medline]
- Siewert JR, Stein HJ, Feith M, Bruecher BL, Bartels H, Fink U. Histologic tumor type is an independent prognostic parameter in esophageal cancer: lessons from more than 1,000 consecutive resections at a single center in the Western world Ann Surg 2001;234:360-367.[Medline]
- Rice TW, Blackstone EH, Rybicki LA, et al. Refining esophageal cancer staging J Thorac Cardiovasc Surg 2003;125:1103-1113.[Abstract/Free Full Text]
- Demeester SR. Lymph node involvement in esophageal adenocarcinoma: if you see one, have you seen them all? J Thorac Cardiovasc Surg 2003;126:947-949.[Free Full Text]
- Nakagawa S, Kanda T, Kosugi S, Ohashi M, Suzuki T, Hatakeyama K. Recurrence pattern of squamous cell carcinoma of the thoracic esophagus after extended radical esophagectomy with three-field lymphadenectomy J Am Coll Surg 2004;198:205-211.[Medline]
- Siewert JR, Fink U, Beckurts KT, Roder JD. Surgery of squamous cell carcinoma of the esophagus Ann Oncol 1994;5(suppl 3):1-7.[Medline]
- Akiyama H, Tsurumaru M, Udagawa H, Kajiyama Y. Radical lymph node dissection for cancer of the thoracic esophagus Ann Surg 1994;220:364-372.[Medline]
- Hagen JA, DeMeester SR, Peters JH, Chandrasoma P, DeMeester TR. Curative resection for esophageal adenocarcinoma: analysis of 100 en bloc esophagectomies Ann Surg 2001;234:520-530.[Medline]
- Eloubeidi MA, Desmond R, Arguedas MR, Reed CE, Wilcox CM. Prognostic factors for the survival of patients with esophageal carcinoma in the U.S.: the importance of tumor length and lymph node status Cancer 2002;95:1434-1443.[Medline]
- Roder JD, Busch R, Stein HJ, Fink U, Siewert JR. Ratio of invaded to removed lymph nodes as a predictor of survival in squamous cell carcinoma of the oesophagus Br J Surg 1994;81:410-413.[Medline]
- Waterman TA, Hagen JA, Peters JH, DeMeester SR, Taylor CR, Demeester TR. The prognostic importance of immunohistochemically detected node metastases in resected esophageal adenocarcinoma Ann Thorac Surg 2004;78:1161-1169.[Abstract/Free Full Text]
- Lerut T, Coosemans W, Decker G, et al. Collaborative Workgroup for Esophageal Carcinoma Extracapsular lymph node involvement is a negative prognostic factor in T3 adenocarcinoma of the distal esophagus and gastroesophageal junction J Thorac Cardiovasc Surg 2003;126:1121-1128.[Abstract/Free Full Text]
- Nishimaki T, Suzuki T, Suzuki S, Kuwabara S, Hatakeyama K. Outcomes of extended radical esophagectomy for thoracic esophageal cancerOutcomes of extended radical esophagectomy for thoracic esophageal cancer. J Am Coll Surg 1998;186:306-312.[Medline]
- Dhar DK, Tachibana M, Kinukawa N, et al. The prognostic significance of lymph node size in patients with squamous esophageal cancer Ann Surg Oncol 2002;9:1010-1016.[Medline]
- Dhar DK, Kubota H, Kinukawa N, et al. Prognostic significance of metastatic lymph node size in patients with gastric cancer Br J Surg 2003;90:1522-1530.[Medline]
- Dhar DK, Yoshimura H, Kinukawa N, et al. Metastatic lymph node size and colorectal cancer prognosis J Am Coll Surg 2005;200:20-28.[Medline]
- Ide H, Nakamura T, Hayashi K, et al. Esophageal squamous cell carcinoma: pathology and prognosis. World J Surg 199;18:321–30.
- Doi N, Imada T, Aoyama N, Kameda Y, Koizumi H. Prognostic significance of the carcinoma area in the thickest part of the lymph node Hepatogastroenterology 2000;47:728-732.[Medline]
- Komori T, Doki Y, Kabuto T, et al. Prognostic significance of the size of cancer nests in metastatic lymph nodes in human esophageal cancers J Surg Oncol 2003;82:19-27.[Medline]
- Fok M, Law SY, Wong J. Operable esophageal carcinoma: current results from Hong Kong World J Surg 1994;18:355-360.[Medline]
- Igaki H, Kato H, Tachimori Y, Nakanishi Y, Shimoda T. Surgery for clinical T3 carcinomas of the upper thoracic oesophagus and the need for new strategies Br J Surg 2005;92:1235-1240.[Medline]
- Japanese Society for Esophageal Diseases Guide lines for the clinical and pathologic studies on carcinoma of the esophagus Jpn J Surg 1976;6:69-78.[Medline]
- Siewert JR, Bottcher K, Stein HJ, Roder JD. Relevant prognostic factors in gastric cancer: ten-year results of the German Gastric Cancer Study Ann Surg 1998;228:449-461.[Medline]
- Inoue K, Nakane Y, Iiyama H, et al. The superiority of ratio-based lymph node staging in gastric carcinoma Ann Surg Oncol 2002;9:27-34.[Medline]
- van Sandick JW, van Lanschot JJ, ten Kate FJ, Tijssen JG, Obertop H. Indicators of prognosis after transhiatal esophageal resection without thoracotomy for cancer J Am Coll Surg 2002;194:28-36.[Medline]
- Tachibana M, Kinugasa S, Yoshimura H, Dhar DK, Nagasue N. Extended esophagectomy with 3-field lymph node dissection for esophageal cancer Arch Surg 2003;138:1383-1389.[Abstract/Free Full Text]
- Altorki NK, Skinner DB. Occult cervical nodal metastasis in esophageal cancer: preliminary results of three-field lymphadenectomy J Thorac Cardiovasc Surg 1997;113:540-544.[Abstract/Free Full Text]
- Korst RJ, Rusch VW, Venkatraman E, et al. Proposed revision of the staging classification for esophageal cancer J Thorac Cardiovasc Surg 1998;115:660-669.[Abstract/Free Full Text]
- Lerut T, Nafteux P, Moons J, et al. Three-field lymphadenectomy for carcinoma of the esophagus and gastroesophageal junction in 174 R0 resections: impact on staging, disease-free survival, and outcome: a plea for adaptation of TNM classification in upper-half esophageal carcinoma Ann Surg 2004;240:962-972.[Medline]
- Luketich JD, Schauer PR, Meltzer CC, et al. Role of positron emission tomography in staging esophageal cancer Ann Thorac Surg 1997;64:765-769.[Abstract/Free Full Text]
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Abstract
Introduction
