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10.1245/s10434-006-9166-x
Annals of Surgical Oncology 14:306-316 (2007)
© 2007 Society of Surgical Oncology
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Original Article

Lymphadenectomy for Adenocarcinoma of the Gastroesophageal Junction (GEJ): Impact of Adequate Staging on Outcome

Andrew P. Barbour1, Nabil P. Rizk1, Mithat Gonen2, Laura Tang3, Manjit S. Bains1, Valerie W. Rusch1, Daniel G. Coit1 and Murray F. Brennan, MD1

1 Department of Surgery, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA
2 Department of Epidemiology-Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA
3 Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA

Correspondence: Address correspondence and reprint requests to: Murray F. Brennan, MD; E-mail: brennanm{at}mskcc.org


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Introduction: Adequate staging of gastric cancer requires examination of at least 15 lymph nodes. Most resected patients are inadequately staged potentially confounding the interpretation of clinical data. The aim of this study was to determine whether adequate staging revealed different prognostic factors or improved survival compared with patients with <15 nodes examined after R0 resection for GEJ cancer.

Methods: A prospectively maintained database identified 366 patients with Siewert types II and III adenocarcinoma of the GEJ who underwent R0 resection without neoadjuvant therapy at a single institution. Patients were grouped into adequately (≥ 15 nodes examined) or inadequately staged (<15 nodes examined). Median follow up was 51 months.

Results: From 1985 through 2003, 250/366 (68%) patients were adequately staged and 116/366 (32%) were inadequately staged. There was no difference in operative mortality between adequately staged (5.2%) and inadequately staged patients (4.3%, P = NS). Adequately staged patients had more positive lymph nodes (median 2) compared with inadequately staged patients (median 1, P < 0.01). Multivariable analysis of adequately staged patients found the number of positive lymph nodes, T stage, and lymphovascular invasion to be independent prognostic factors for overall survival (OS). For inadequately staged patients only the number of positive lymph nodes and T stage were independent prognostic factors. Adequate staging was an independent prognostic factor for patients with advanced (T ≥ 2 Nany) tumors. For T1 tumors adequate staging was not associated with improved survival.

Conclusions: Patients with GEJ cancer should undergo adequate lymphadenectomy to permit examination of ≥ 15 lymph nodes allowing the accurate identification of prognostic variables. Removal of ≥ 15 lymph nodes is associated with more accurate survival estimates for patients with advanced disease.

Key Words: Gastroesophageal junction • Adenocarcinoma • Staging • Prognostic factors • Lymphadenectomy


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Outcomes for GEJ cancer remains poor and a variety of adjuvant protocols have been investigated.1–5 The principal therapeutic component of these trials, the operation, has had little quality control. Adequate lymphadenectomy was strongly recommended in the induction chemotherapy trial reported by Kelsen et al.,1 but no mention of the extent of lymph node involvement was made in the results. In the OEO2 trial, up to 30% of prescribed lymph nodes stations were not examined.2 The INT116 trial recommended D2 lymphadenctomy, but that "recommendation" was made post-operatively and was performed in 10% of cases.3 It has been proposed that surgical undertreatment may have undermined survival.6 Despite discrepancies between specific sites or numbers of positive nodes and outcome, the presence of any lymph node metastases is universally associated with a poor prognosis compared with node-negative patients.7 Because small variations in N stage distribution between treatment arms of a trial could have a significant impact on the final result, there is a need for consistency in the staging of GEJ cancer for future clinical trails.

The optimal extent of lymphadenectomy remains controversial in surgery for cancer of the gastro-esophageal junction (GEJ). Randomized trials have failed to show a benefit for D2 lymphadenectomy,8,9 while specialist units have shown that it can be done with low morbidity and mortality.10,11 Two-field lymphadenectomy has been proposed for GEJ cancer in order to improve both staging12 and outcome,13–15 but the data regarding the prevalence of lymph node metastases in specific stations is inconsistent. Clinical series report rates of mediastinal nodal involvement that vary from 7 to 40% for types II and III GEJ cancer with abdominal nodes being the more common sites of lymphatic metastasis for these tumors.12,16,17 Similar to gastric cancer, randomized trials in esophageal and GEJ cancer have not shown a benefit for more radical surgery in the form of transthoracic esophagectomy with two-field lymphadenectomy over transhiatal esophagectomy.18,19 Three-field lymphadenectomy has been shown to provide more accurate staging by identifying cervical lymph node metastases that may be involved in up to 17% of patients with types II and III GEJ cancer.20 The supporters of this approach suggest it had a survival benefit for esophageal cancer, but not for GEJ cancer20 although this suggestion is made based upon retrospective observations and not prospective randomized data. The specific sites of lymph node metastases, other than cervical,20 have not shown a consistent relationship with outcome.21

The current AJCC staging system for gastric cancer is based on the number, rather than the site of positive lymph nodes. This system requires the pathological assessment of at least 15 lymph nodes for patients to be considered adequately staged.22 Despite this recommendation, only 18% of gastric cancer resections are adequately staged in North America.23 The figures for surgery of the GEJ are likely to be similar in general surgical practice.

This study was undertaken in order to determine whether adequate staging (pathological assessment of at least 15 lymph nodes) identifies different prognostic factors in GEJ cancer compared with inadequately staged patients, and whether adequately staged patients exhibit improved survival.


   PATIENTS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
A prospectively maintained esophagogastric cancer database identified 366 patients with Siewert types II and III adenocarcinoma of the GEJ that underwent R0 resection without neoadjuvant therapy at the Memorial Sloan-Kettering Cancer Center from July 1985 to November 2003. Adenocarcinoma of the GEJ was defined as a tumor with the center within 5 cm proximal and distal of the anatomical gastroesophageal junction. Patients with high grade dysplasia (HGD) only were excluded. Demographic, pathologic, and treatment-related variables, including operative approach and type of lymphadenectomy, were prospectively recorded. Tumor location was further prospectively classified by clinicians and pathologists according to the anatomical criteria described by Siewert:24 type I –5 to –2 cm from the true cardia; type II –1 to +2 cm; type III +2 to +5 cm from the gastroesophageal junction.

Lymphadenectomy
All patients had their primary tumors resected at the Memorial Sloan-Kettering Cancer Center during the study period. All operations were performed with curative intent. The type of lymphadenectomy was indicated by the operating surgeon. D2 lymphadenectomy included lymph node stations 1–11 (excluding station 6), 19 and 20 in accordance with the guidelines of the Japanese Research Society for Gastric Cancer.25 Procedures where any of these lymph node stations were not included in the lymphadenectomy were defined as less than D2 lymphadenectomy. Proximal gastrectomy (PG) was defined as resection of the proximal stomach with intra-abdominal esophagogastric anastomosis and total gastrectomy (TG) was the removal of the entire stomach and proximal duodenum with intra-abdominal esophagojejunal reconstruction. Esophagogastrectomy was defined as resection of the proximal stomach and thoracic esophagus with anastomosis in the chest performed via left thoracoabdominal incision (thoracoabdominal); or right thoracotomy (TTE) with esophagogastric anastomosis in the chest (Ivor Lewis operation) or neck (three-phase operation); or via transhiatal approach with anastomosis in the neck (THE). The choice of operation type was based on the site of the tumor and surgeon preference with the aim of removing the primary tumor in its entirety and its draining lymphatics. Procedure-related mortality was defined as death in hospital or within 30 days of operation.

Pathological Analysis
Tumor grade and stage were assessed by experienced gastrointestinal pathologists and classified according to the sixth edition of the TNM staging system of the American Joint Committee on Cancer (AJCC) for gastric cancer.22 All possible lymph nodes associated with gastroesophagectomy specimens were dissected from the paraesophageal and paragastric soft tissue. Separate lymph nodes, which were dissected during the operation by surgeons, were entirely submitted for histopathologic assessment. Lymph nodes greater than 1.0 cm in diameter were bisected, submitted en face, and counted as single lymph nodes. In most cases, lymph node status was evaluated by routine hematoxylin and eosin (H&E) stained section. Patients were grouped into adequately (≥ 15 nodes examined) or inadequately staged (<15 nodes examined).

Statistical Analysis
Statistical analysis was carried out with SPSS for Windows, version 12.0 (Statistical Package for the Social Sciences, SPSS, Inc., Chicago, IL, USA), SAS, version 9.0 (Statistical Analysis System, Cary, NC, USA) and R version 2.0 (http://www.r-project.org). Continuous variables were expressed as median (range) and compared using the Wilcoxon test, whereas categoric variables were compared using the {chi}2 or Fisher’s exact test. Follow up time was calculated from the date of definitive surgery. Overall survival probabilities were estimated by the Kaplan–Meier method, including postoperative deaths, with differences in survival rates assessed using the log-rank test to determine univariate significance. Factors that were deemed of potential importance on univariate analysis (P < 0.05) were included in the multivariate analysis. Proportional hazards regression was used for multivariate analysis of these factors. Continuous variables that were significant were categorized using the maximal {chi}2 method.26


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
Demographics
The male-to-female ratio was 4:1 and the median age was 66 (range 25–90 years) for the 366 study patients. The clinicopathological characteristics of the patients are displayed in Table 1Go. There were 18 (4.9%) procedure-related deaths. The median overall survival (OS) was 30 months for the entire cohort and the median follow-up was 51 months for survivors.


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  		TABLE 1. Patient demographics and pathological stage
 
Clinical Factors
There were 264 patients (72%) with Siewert type II and 102 patients (28%) with Siewert type III invasive adenocarcinoma of the GEJ. There were 196/366 (54%) patients with T3 tumors and 61% had node-positive disease. The median tumor size was 4.0 cm (range 0.1–13 cm). Lymphovascular invasion (LVI) was present in 145/366 (40%) and LVI was not available for two patients. Perineural invasion (PNI) was present in 175/366 (48%) and PNI was not available for one patient. Tumor differentiation was reported as poor (n = 186 or 51%), moderate (n = 146 or 40%) or well differentiated (n = 29 or 8%). Tumor differentiation was not available for 5/366 patients. Post-operative chemotherapy was administered to 8/366 (2%) patients and 7/366 (2%) patients received post-operative chemoradiotherapy.

Lymphadenectomy and Adequate Staging
Of the 366 patients, 250 (68%) were adequately staged and 116 (32%) were inadequately staged. Prior to the introduction of the revised AJCC staging system in 1997, 136/208 (65%) patients were adequately staged compared with 115/158 (73%) patients treated after the introduction of the new staging system. This difference was not statistically significant (P = 0.14, Fisher’s exact test). There was no difference in operative mortality between adequately staged (5.2%) and inadequately staged patients (4.3%, P = NS). There were no differences between adequately and inadequately stage patients with respect to age, gender, T stage, tumor size (in cm), AJCC stage, LVI, PNI or tumor differentiation (poor versus well or moderate) (Table 2Go). In contrast, adequately staged patients were significantly higher N stage (P < 0.01) and had more positive lymph nodes (median 2, range 0–29) compared with inadequately staged patients (median 1, range 0–11, P < 0.01, Table 2Go).


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  		TABLE 2. Comparison of clinicopathological variables for adequately and inadequately staged patients
 
There was no significant difference in operative mortality rate between less than D2 lymphadenectomy (2.9%) and D2 or greater lymphadenectomy (5.8%). D2 lymphadenectomy was associated with significantly more lymph nodes examined (median 21) than less extensive lymphadenectomies (median 14, P < 0.01). Adequate staging was achieved in 180/243 (74%) patients that underwent D2 lymphadenectomy, compared with 34/69 (49%) patients that underwent less than D2 lymphadenectomy (P < 0.01).

The majority of patients (51%) underwent procedures with one field (abdominal only) lymphadenectomy, including total gastrectomy (n = 13) or proximal gastrectomy via laparotomy (n = 53) or left thoracoabdominal (n = 63) and transhiatal esophagectomy (n = 59). The remainder of the patients were treated with two-field (abdominal and thoracic) lymphadenectomy by Ivor Lewis (n = 159) or three-phase esophagectomy (n = 11). The type of procedure was unavailable for eight patients. There was no significant difference in operative mortality rate between one-field (5.9%) and two-field lymphadenectomy (4.1%, P = 0.48). Compared with one-field lymphadenectomy, two-field lymphadenectomy resulted in a higher rate of adequate staging (62% compared with 75%, P < 0.01) and a higher number of nodes examined (median 18 versus 22, P < 0.01).

Prognostic Variables
Factors associated with survival for all patients were determined by Kaplan–Meier and log rank analyses (Table 3Go). Univariable analyses identified T stage, tumor size >4 cm, N stage, number of positive lymph nodes, number of negative lymph nodes, LVI, PNI and poor differentiation as prognostic factors. Siewert type, age, gender, post-operative therapy and the type of lymphadenectomy were not prognostic factors. Multivariable analysis identified the number of positive nodes, T stage, LVI and the number of negative nodes as independent prognostic factors (Table 3Go).


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  		TABLE 3. Univariable and multivariable prognostic factors for 366 Siewert types II and III GEJ cancer undergoing R0 resection
 
Univariable Kaplan–Meier and log-rank survival analyses were undertaken separately for patients that were adequately and inadequately staged in order to determine whether adequate lymph node staging impacted on the identification of significant clinicopathological factors (Table 4Go). For adequately staged patients T stage was a significant prognostic factor and there were significant survival differences observed between T1 and T2 (P = 0.008, log rank), T1 and T3 (P < 0.001, log rank), and T2 and T3 tumors (P = 0.001, log rank). For inadequately staged patients, no significant survival difference was observed between T2 and T3 tumors (P = 0.58, log rank), but T1 tumors showed significantly better survival than T2 (P < 0.001, log rank) and T3 tumors (P < 0.001, log rank). Other significant prognostic factors for both adequately and inadequately staged patients were N stage, number of positive nodes, number of negative nodes, LVI, PNI, poor differentiation, and tumor size >4 cm (Table 4Go). Siewert type, age, gender and the type of lymphadenectomy were not prognostic variables.


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  		TABLE 4. Univariable prognostic factors for adequately (n = 250) and inadequately staged patients (n = 116)
 
Multivariable analysis of adequately staged patients using a model that incorporated T stage, number of positive nodes, number of negative nodes, LVI, PNI, differentiation and tumor size >4 cm found in addition to the number of positive lymph nodes, T stage, LVI, and differentiation to be independent prognostic factors for overall survival (OS) (Table 5Go). In contrast, only the number of positive lymph nodes and T stage were found to be independent prognostic factors for inadequately staged patients using the same multivariable model (Table 5Go). Finally, we examined the association between percentage of positive lymph nodes compared to total nodes examined (dichotomized to ≤10 and >10% positive nodes) and survival for inadequately staged patients. Multivariable analyses found that >10% positive lymph nodes was not a significant prognostic factor for inadequately staged patients (data not shown).


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  		TABLE 5. Multivariable analysis of 250 adequately staged patients and 116 inadequately staged patients
 
Impact of Staging on Survival
Having established that adequate staging had an impact on prognostic variables, we sought to determine whether adequate staging and type of lymphadenectomy affected actuarial survival. The prevalence of regional lymph node metastasis in GEJ cancer is proportional to the depth of tumor invasion. As a result, the value of extended lymphadenectomy for early gastric and esophageal cancer has been questioned. Therefore, we analysed the impact of adequate staging separately for early, that is T1 Nany (n = 73), and advanced, that is T ≥ 2 Nany, GEJ tumors (n = 293). First, the impact of adequate staging on 73 T1 Nany patients was analyzed. Univariable analysis revealed that adequate staging was not associated with improved actuarial survival for the node-negative early GEJ cancer patients (n = 67, median survival not reached, 5-year survival 77% for adequately staged compared with 73% for inadequately staged, Fig. 1aGo, Kaplan–Meier method, P = 0.93). The type of lymphadenectomy was not associated with improved survival (data not shown). Positive lymph nodes were identified in 5/48 (10%) adequately staged patients compared with 1/24 (4%) inadequately staged patients (P = 0.65). Survival analyses were not undertaken for this group due to the small sample size.


Figure 1
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  		FIG. 1. Kaplan–Meier overall survival analysis for adequately and inadequately staged T1 node-negative patients with Siewert types II and III GEJ adenocarcinoma that underwent R0 resection (P = 0.93, log rank).

 
For 293 patients with advanced tumors, that is ≥T2 Nany, survival analyses were stratified by AJCC N stage in order to determine whether adequate staging resulted in significant stage migration. For the 79 patients with node-negative advanced tumors, adequate staging resulted in significantly better survival estimates (n = 49, median survival 76 months) compared with inadequate staging (n = 30, median survival 35 months, Table 6Go, P < 0.05, log rank). Compared with inadequate staging, adequate staging also resulted in significantly better actuarial survival for the ≥T2 N1 and ≥T2 N2 groups (Table 6Go). Inadequate staging had the effect of "upstaging" the N stage for this group of patients with ≥T2 tumors (Fig. 2Go). Inadequately staged N0 patients (n = 30, median survival 35 months) demonstrated similar survival to adequately staged N1 patients (n = 95, median survival 27 months, Fig. 2AGo,P = 0.79, log rank), and inadequately staged N1 patients (n = 49, median survival 17 months) demonstrated similar survival compared with adequately staged N2 patients (n = 43, median survival 18 months, Fig. 2BGo,P = 0.40, log rank). There was no difference in survival between inadequately staged N2 (n = 12, median survival 11 months) and adequately staged N3 patients (n = 17, median survival 9 months, Fig. 2CGo,P = 0.89, log rank). In contrast, the type of lymphadenectomy (less than D2 versus D2 or greater, or one-field versus two-field) was not of prognostic significance for any N stage (data not shown).


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  		TABLE 6. Effect of adequate and inadequate staging on actuarial survival for 73 patients with early (T1) tumors and 293 patients with advanced (≥T2) tumors, stratified by N stage
 

Figure 2
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  		FIG. 2. (A) Kaplan–Meier overall survival analysis N0 (n = 49, P = 0.03) and N1 (n = 95, P = NS) adequately staged compared with N0 (n = 30) inadequately staged Siewert types II and III GEJ adenocarcinoma patients with advanced (T2 or greater) tumors that underwent R0 resection. (B) Kaplan–Meier overall survival analysis for adequately staged N1 (n = 95, P = 0.03) and N2 (n = 43, P = NS) patients compared with inadequately staged N1 (n = 49) patients with advanced (T2 or greater) tumors that underwent R0 resection. (C) Kaplan–Meier overall survival analysis for adequately staged N2 (n = 43, P = 0.05) and N3 (n = 17, P = NS) patients compared with inadequately staged N2 (n = 12) patients.

 

   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
The goal of surgery for cancer of the GEJ is R0 resection, but the optimal extent of lymphadenectomy remains controversial. Siewert and collegues,7 who described the anatomical classification of GEJ tumors, applies the AJCC gastric staging system to types II and III adenocarcinoma. Adherence to gastric cancer nodal staging systems that relied on the site of positive lymph nodes relative to primary was historically poor. In 1997, the AJCC redefined the pathological nodal status based on the number of involved nodes and this has been shown to be associated with more accurate survival estimates compared with older, location-based staging.22,41 The current AJCC staging system for gastric cancer requires the assessment of at least 15 lymph nodes for patients to be adequately staged. This provides a minimum standard for both the surgery and pathological analysis of this disease. In this study, we have demonstrated that adequately staged patients have additional prognostic factors compared with inadequately staged patients. Furthermore, for patients with advanced GEJ cancer adequate staging was associated with improved survival estimates.

The multivariable analyses of adequately and inadequately staged patients revealed T stage and the number of positive lymph nodes to be independent prognostic factors. Both T and N stage form the basis of the AJCC staging system for esophageal and gastric cancer,22 but N stage with increasing number of positive nodes have consistently been shown to be the strongest prognostic factors for GEJ cancer following R0 resection, as demonstrated in this study.7,27,28 The assessment of ≥15 lymph nodes ensures accurate N staging that permits the identification of additional prognostic factors that may allow further refinement of the AJCC staging system. The adequacy of the AJCC staging system for GEJ cancer has been questioned as either the gastric or esophageal system may be used.29 We performed the analyses in this study on a homogeneous group of patients (all with adenocarcinoma and R0 resection) using prognostic variables previously validated in a nomogram for gastric and GEJ cancer that has been shown to more accurately predict outcome than the AJCC system.30,31

The present study highlights the importance of poor differentiation and LVI as prognostic factors for adequately staged patients. Previous studies of esophageal adenocarcinoma have also shown tumor grade to be of prognostic significance while Langley et al.32 did not. Similarly, the prognostic significance of tumor grade in gastric cancer is also inconsistent.33,34 Lymphovascular invasion has been shown to be of prognostic significance in esophageal35 and gastric cancer.36,37 For types II and III GEJ cancer, Von Rahden et al.38 reported not only that LVI was a prognostic factor, but that it was a more powerful predictor of outcome than T stage or R status. Our data further support LVI as a determinant of outcome. We did not find LVI or poor differentiation to be prognostic factors for inadequately staged patients. This may be due to a lack of power to detect statistical significance. An alternative explanation for this observation may be that for the adequately staged, the number of positive lymph nodes is assigned the appropriate prognostic significance (HR 1.06/positive node) allowing the effect of other variables on survival to be assessed. This contrasts with the inadequately staged group in which the number of positive nodes carries a higher risk of death (HR 1.21), representing the likelihood that for a patient to be node-positive in the setting of an inadequate lymph node sampling they are likely to have a higher number of truly positive lymph nodes and hence a worse prognosis. Inconsistency in the significance of grade and LVI in previous studies may be due to the inclusion of inadequately staged patients. While we wait for consistency in molecular staging, this study supports incorporating these additional clinicopathological variables into future staging systems or nomograms. Furthermore, tumor differentiation and LVI should be included as standard in pathology reports.

Adequate staging was achieved in 68% of patients in this series without additional mortality. Similarly, both D2 and two-field lymphadenectomy demonstrated similar operative mortality rates compared with less than D2 and one-field lymphadenectomy, respectively. These findings are similar to those of other high volume centers that have shown that extended lymphadenectomy can be achieved with acceptable mortality,15,39,40 whereas in the broader setting of multicenter trials, more radical lymphadenectomy has been associated with increased morbidity and mortality.9,18 Thus, adequate staging can be achieved without additional risk in a specialist unit. Extended lymphadenectomies in the form of D2 and two-field procedures were associated with higher rates of adequate staging in this series. However, there were still a significant number of patients that underwent less than D2 lymphadenectomy that were adequately staged, similar to our experience with gastric cancer.41 These data argue that pathological assessment of the specimen is as important as surgical quality control42 with techniques such as fat clearing able to increase lymph node numbers twofold.43

Adequate staging was associated with improved outcome for the majority of patients with types II and III GEJ cancer following R0 resection. In the analysis of the subgroups, adequate staging lost its significance for T1 patients. This is not a surprising finding given that the prevalence of positive lymph nodes in early gastric44 and esophageal cancer45 is less than 20% and, therefore, inadequately staged T1 N0 patients are likely to be truly node-negative. In contrast, a significant improvement in prognosis was seen for adequately staged T2 or 3 N0 and node-positive patients. This group of patients with advanced disease has a high prevalence of positive nodes and the examination of ≥15 lymph nodes would be expected to identify positive nodes that might be missed with less rigorous lymph node sampling. Evidence of such stage migration associated with adequate staging was apparent for the patients with advanced tumors. For patients with greater than T2 tumors, inadequate staging effectively upstaged the N stage of these patients compared with adequately staged patients. In contrast, the type of lymphadenectomy (less than D2 versus D2 or greater; one-field versus two-field) was not associated with improved outcome. These data are consistent with the results of randomized trials in gastric cancer8,9 and esophageal and GEJ cancer18 that failed to show a benefit for extended lymphadenectomy. There was significant overlap between adequacy of staging and type of lymphadenectomy in the present study. These findings argue that the improved survival associated with adequate staging was largely due to stage migration, rather than treatment effect and builds upon previous studies in gastric cancer that have shown improved survival for stages II and III patients that have ≥15 nodes examined.23,41

This study shows that surgical (and pathological) quality control, in the form of adequate staging, has an impact on estimation of prognosis for patients with Siewert types II and III GEJ cancer that have undergone R0 resection. Chemotherapy and radiotherapy are standardized in adjuvant trials, but to date surgery has not. The multicenter nature of these trials and the need to recruit clinicians to participate in the studies has made it difficult to be prescriptive with surgery in the past.8 As surgical oncologists, we need to move forward with the treatment of GEJ cancer and perform an adequate lymphadenectomy to permit the assessment of ≥15 lymph nodes. In the appropriate setting, adequate staging can be achieved without additional mortality. This will permit more accurate prognostication for individual patients and facilitate the interpretation of future clinical trials.


   ACKNOWLEDGMENTS
 
The authors thank Marianne Beninati for her assistance and meticulous data acquisition.

Received for publication July 2, 2006. Accepted for publication July 3, 2006.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

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