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10.1245/s10434-006-9218-2
Annals of Surgical Oncology 14:317-328 (2007)
© 2007 Society of Surgical Oncology
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Original Article

Clinical impact of lymphadenectomy extent in resectable gastric cancer of advanced stage

Roderich E. Schwarz1 and David D. Smith2

1 Division of Surgical Oncology (RES), The Cancer Institute of New Jersey, New Brunswick, NJ 08903, USA
2 Division of Biostatistics (DDS), City of Hope Cancer Center, Duarte, CA 91010, USA

Correspondence: Address correspondence and reprint requests to: Roderich E. Schwarz, Department of Surgery, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, The Cancer Institute of New Jersey, 195 Little Albany Street, New Brunswick, NJ 08901, USA; E-mail: r.schwarz{at}umdnj.edu


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Background: Advanced, but potentially still curable gastric cancer (stages IIIA, IIIB, or stage IV M0) is associated with very high recurrence rates after gastrectomy. The value of an extended lymph node dissection (ELND) remains unclear in this setting.

Methods: A resected gastric cancer data set was created through structured queries to the SEER 1973–2000 database. Relationships between the number of lymph nodes (LNs) examined and survival outcomes were analyzed for the stage subgroups characterized by the N categories N2 or N3, and transmural tumor extension (T categories T2b or T3).

Results: The study group encompassed 1,377 patients, including T2b/3N2 (n = 1,076) and T2b/3N3 stage subgroups (n = 301). Total LN count (or number of negative LNs examined; P < 0.0001), number of positive LNs (P < 0.0001), age (P < 0.0001), primary site (P = 0.0002), T category (P = 0.0271), race (P = 0.0301) and gender (P = 0.0261) were independent prognostic survival predictors. A cut point analysis yielded the ability to detect significant survival differences for LN numbers up to 30 (N2) or up to 40 (N3), always in favor of the higher number of LNs examined. Best long-term survival outcomes were observed with negative LN counts of more than 15 (N2) or more than 20 (N3).

Conclusions: Even in transmural or serosa-positive gastric cancer with advanced nodal involvement, more extensive LN dissection and analysis influences survival. Stage-based survival prediction depends on total LN number and number of negative LNs. The mechanism remains uncertain, but is not limited to stage migration. ELND during potentially curative gastrectomy is recommended even for advanced gastric cancer.


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Gastric cancer remains a therapeutically challenging disease, with an estimated overall 5-year survival rate of 23% in the United States.1 Despite recent advances in multimodality treatment and targeted therapy, complete resection remains the mainstay of curative gastric cancer therapy. The majority of patients with gastric cancer in the United States present with advanced stages, and the majority of patients who undergo gastrectomy are found to have meta-static nodal involvement.2–4 Pathologic T and N staging criteria are the main prognostic determinants for completely resected gastric cancer after curative intent gastrectomy.5–7 Unfortunately, advanced, but potentially still curable (stages IIIA, IIIB, or stage IV M0) gastric cancer is associated with very high recurrence rates, even after R0 gastrectomy.8,9 Although attempts to control regionally advanced disease through wider resections have been described as early as 50 years ago and are more widely practiced in Asian and European centers,10,11 the value of an extended lymph node dissection (ELND) still remains debated in this setting. The rationale in favor of ELND includes the potential to provide more appropriate pathologic staging, better regional disease control, and possibly some survival advantage. For example, the diagnosis of N3 disease requires the examination of at least 16 LNs by definition, which is more likely accomplished with a retroperitoneal LN dissection in addition to a simple gastrectomy. Nevertheless, two European prospective randomized trials of D2 dissections at gastrectomy for gastric cancer have failed to demonstrate an overall survival benefit,12,13 but these findings are influenced by increased morbidity and mortality due to higher splenectomy and pancreatectomy rates in the D2 dissection groups.14,15 Long-term survival outcomes in the Dutch trial have suggested a superior survival after D2 dissection for patients with intermediate nodal involvement of N2 category.16 Recently, we have linked numeric LN counts to gastric cancer survival in patients with resected T1-3N0-1 disease, using information from a large U.S. population-based database.17 While stage migration appeared to be an obvious mechanism to explain some of this effect, better survival was observed for all early-stage subgroups at LN count cutoff points of up to 40. This finding suggests that another mechanism related to better regional disease clearance might possibly contribute to the improved survival. Our hypothesis was that if LN counts impact on postoperative survival therapeutically, that such benefits would also be discernable in regionally advanced stage groups. We thus investigated the relationship between LN numbers examined after gastrectomy and survival for transmural gastric cancers (T2b and T3) with N2 or N3 nodal categories, based on information from the Surveillance, Epidemiology, and End-Results (SEER) data set published by the National Cancer Institute. These stage subgroups were of interest for the analysis of numeric LN impact because of the suggested D2 dissection benefit in the Dutch trial (to the N2 subgroup), and in order to minimize the possibility of stage migration due to larger LN numbers examined by selecting the highest nodal stage category (N3).


   PATIENTS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
A gastric cancer data set was created through structured queries to the public version SEER 1973–2000 database, which includes combined records from 14 cancer registries within the United States.18 Stage information was created according to 6th edition American Joint Committee on Cancer Tumor Node Metastasis (AJCC TNM) criteria.19 Recoding of data for stage subcategory assignment was performed as outlined in detail before.17 In this analysis, relationships between the number of LNs examined and survival outcomes were analyzed only for the stage subgroups characterized by the N categories N2 or N3, and transmural tumor extension (T categories T2b or T3). T4 lesions were not included to avoid data heterogeneity, as resections in these cases were expected to be more extensive, and the likelihood for positive margins was judged to be higher. From a cohort of 65,560 patients, individuals were selected based on completeness of information, M0 status, with at least 7 (N2) or 16 (N3) LNs examined, and exclusive treatment through operation. Patients with incomplete information regarding gastrectomy status or grade, and those who had received additional treatment in form of chemotherapy or radiation, were excluded from the analysis. Similarly, patients with positive resection margins, whenever stated, were not included. The process of data extraction through database queries is depicted in Fig. 1Go.


Figure 1
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  		FIG. 1. Surveillance, Epidemiology, and End-Results (SEER) database data extraction process.

 
Overall survival was the primary outcome component of interest. The survival time as tabulated by SEER was the time from diagnosis until last contact, date of death, or the date used as a cutoff for the SEER database, in which case the survival information was censored. For the entire cohort, and in part for each stage subgroup, survival was analyzed through univariate, multivariate, cut point, and model projection statistics as previously applied.17 Actuarial survival was determined via the Kaplan-Meier method,20 with univariate comparisons between groups through the log-rank test.21 A regression model to correlate total LN counts with survival was obtained based on Kaplan-Meier 5-year survival estimates for each LN count interval, using the LN count interval midpoints to construct the independent variable.17 Cox regression was used for multivariate analysis, with a backward elimination model for all covariates.22 The threshold for keeping a variable in this elimination model was P = 0.05. Variables included into this multivariate calculation were: grade, T stage category (T2b versus T3), total number of LNs examined (and/or number of negative LNs), number of positive LNs, race, age, gender, tumor size, year of diagnosis, and tumor location. To link survival outcomes with LN count categories, we used Monte Carlo simulation for exact P values of the Kruskal-Wallis test as implemented in StatXact 4.0.1 software (Cytel, Cambridge, MA, USA). All other calculations were performed using the SAS 8.2 statistical software package (SAS, Cary, NC, USA). Simple group data comparisons based on parametric statistics were done via t-test. Significance of differences was assumed at P values of less than 0.05.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
Patient selection based on pathologic stage information
Out of 65,560 patients with gastric cancer in the SEER database, 40,063 were listed to have an adenocarcinoma with sufficient disease extent data to allow a TNM stage classification for further subgroup selection (Fig. 1Go). Of these, 33,180 had M0 disease, and 26,607 had been treated with gastrectomy exclusively. Sufficient surgical pathologic information regarding total number of LNs examined was available for 11,189 individuals. From these, the stage subgroups of interest were extracted. The study group finally selected encompassed 1,377 patients. One thousand seventy-six individuals (78%) had N2 disease, of which 710 were categorized as T2bN2, and 366 as T3N2. Three hundred and one individuals (22%) had N3 disease, of which 173 were staged as T2bN3, and 128 as T3N3. None of these patients had received adjuvant therapy. Eight hundred ninety-one patients were males (65%), and 486 were females (35%). The median age at diagnosis was 68 years, with a range from 20 to 97 years. The primary tumor location was distributed among whole stomach (22%), proximal (26%), middle (28%), and distal tumors (24%), respectively. The median (range) of tumor sizes was 6.0 cm (0.1–18.0 cm); patients with tumors listed as greater than 20 cm (n = 15) had been excluded from the analysis. The tumor grade spectrum included well-differentiated (1%), moderately differentiated (16%), poorly differentiated (79%), and undifferentiated tumors (4%), respectively. The median follow-up for the entire cohort was 13 months (range: 1–140); surviving patients had a median follow-up of 45.5 months (1–140).

Number of LNs examined by stage subgroup
The median number of total LNs examined was 17 for all patients, with a range from 7 to 94. Absolute and relative frequencies of total LN counts by stage subgroup are represented in Fig. 2Go. For patients with either T2b-3N2 gastric cancer stage assignment, the median total LN number was 15 (range: 7–94). In this N2 stage subgroup, 50% of patients had 15 or more LNs examined, and 25% had 20 or more LN analyzed; the median number of positive LNs was 10 (7–15), that of negative LNs 4 (0–84). For the T2b-3N3 subgroup, all individuals had at least 16 LNs examined by definition; the median total LN count was 27 (16–86), with 39% of patients having had 30 or more LNs examined. In this subgroup, the median number of positive LNs was 20 (16–68), that of negative LNs 5 (0–47). There were some differences between T subcategories regarding positive LN counts [T2b: median 10 (7–51); T3: median 11.5 (7–68); Wilcoxon P = 0.0027], but not in total LN counts [T2b: median 16 (7–94); T3: median 17 (7–82); Wilcoxon P = 0.11] or negative LN counts [T2b: median 4 (0–84); T3: median 4 (0–68); Wilcoxon P = 0.34].


Figure 2
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  		FIG. 2. Frequency of categorized number of total lymph nodes examined, for each stage subgroup. a T2b N2 (n=710); b T2b N3 (n=173); c T3 N2 (n=366); d T3 N3 (n=128).

 
Multivariate survival analysis
A multivariate analysis of overall survival was conducted for the entire patient cohort including all stage subgroups. The backwards elimination model yielded these prognostic variables: total LN count (or number of negative LNs examined; P < 0.0001), number of positive LNs (P < 0.0001), age (P < 0.0001), location of the primary within the stomach (P = 0.0002), T category (P = 0.0271), race (P = 0.0301), and gender (P = 0.0342). Information on risk ratio and 95% confidence intervals is listed in Table 1Go. The number of negative LNs obtained, and the total number of LNs examined behaved interchangeably, and maintained a similar significance level when substituted for each other. Co-linearity between these covariates prevented an analysis with simultaneous entry. The covariates tumor size, tumor grade, and the year of diagnosis failed to retain significance levels in this model.


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  		TABLE 1. Parameter estimates and risk ratios for all stage subgroups combined on the basis of the Cox proportional hazards model (n = 1,377)
 
Univariate survival analysis of total LN count impact
Based on a median follow-up of 13 months (45.5 months for survivors), overall survival was calculated for the entire patient cohort and separate stage subgroups. Univariate survival results by stage subgroup and total LN counts are depicted in Figs. 3Go–7GoGoGoGo. At cutoff points of 15, 20, 25, or 30 total LNs examined, overall survival was significantly different, always in favor of the higher LN count. No survival differences were seen for the entire patient cohort at a cutoff of 40 total LNs (Fig. 7Go). For patients with N2 disease, survival rates were significantly better with total LN count comparisons of 20 to 30 (Figs. 4Go–6GoGo); for the N3 subgroup, significant differences were observed for cutoff points of 30 and 40 (Figs. 6Go, 7Go), favoring higher LN counts.


Figure 3
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  		FIG. 3. Actuarial overall survival curve for patients with T2b-3N2 gastric cancer, comparing patients with less than 15 total lymph nodes examined to those with 15 or more total lymph nodes examined. Group survival (in %) over time.

 

Figure 4
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  		FIG. 4. Actuarial overall survival curves, by stage groups, comparing patients with less than 20 total lymph nodes examined to those with 20 or more total lymph nodes examined. A, entire cohort; B, T2b-3N2; C, T2b-3N3. Group survival (in %) over time (in years from diagnosis).

 

Figure 5
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  		FIG. 5. Actuarial overall survival curves, by stage groups, comparing patients with less than 25 total lymph nodes examined to those with 25 or more total lymph nodes examined. A, entire cohort; B, T2b-3N2; C, T2b-3N3. Group survival (in %) over time (in years from diagnosis).

 

Figure 6
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  		FIG. 6. Actuarial overall survival curves, by stage groups, comparing patients with less than 30 total lymph nodes examined to those with 30 or more total lymph nodes examined. A, entire cohort; B, T2b-3N2; C, T2b-3N3. Group survival (in %) over time (in years from diagnosis).

 

Figure 7
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  		FIG. 7. Actuarial overall survival curves, by stage groups, comparing patients with less than 40 total lymph nodes examined to those with 40 or more total lymph nodes examined. A, entire cohort; B, T2b-3N2; C, T2b-3N3. Group survival (in %) over time (in years from diagnosis).

 
When 3-year overall survival was tabulated and compared by increasing total LN count categories, higher LN counts were generally associated with better survival (Table 2Go). For the entire cohort, and for most stage categories except the T2b subgroups, best survival outcomes were observed with total LN counts between 30 and 40. Small patient numbers in the LN count interval of 40 and greater may prevent the detection of additional survival increases. Conversely, the worst survival results were consistently observed at the lowest LN count interval, with the single exception that of the T3N3 subgroup.


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  		TABLE 2. Three-year actuarial overall survival by stage subgroup and total number of lymph nodes examined
 
In an attempt to identify the optimal total LN count cutoff, survival comparisons were created for all stage groups at increasing total LN counts between 10 and 40. This cut point analysis yielded the ability to detect significant survival differences for LN numbers up to 30 (N2) or up to 40 (N3), always in favor of the higher number of LNs examined (Table 3Go). Greatest comparative discrepancies, as measured by the resulting chi-square statistic, were stage group-dependent, and varied from cutoff levels of 20 (T2b-3N2), 30 (T2b-3N3), to 15 (entire cohort).


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  		TABLE 3. Overall survival by total lymph node (LN) count, each stage subgroup cut point analysis for detecting the total lymph node number related to greatest overall survival differences
 
Survival impact of negative LN counts
Three-year survival results, based on categories of increasing counts of negative LNs obtained, showed considerable variations, again with an obvious trend toward better survival results for higher negative LN counts (Table 4Go). The smallest absolute 3-year survival difference between negative LN numeric categories observed was 17% (T2bN3), the largest 42% (T3N2). Generally, negative LN counts of 20 to 30 were linked with best survival results for the entire patient cohort and for most stage subgroups. For the T2bN2 subgroup, best survival results were observed in the category with negative LN counts of 15 to 19; in the T3N3 subgroup, which contains the lowest patient number per cell, this was observed with 10 to 14 negative LNs.


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  		TABLE 4. Three-year actuarial overall survival by stage subgroup and number of negative lymph nodes obtained
 
Projected numeric LN impact on overall survival
Based on the statistically assumed linearity as best fit, LN number impact on overall survival was calculated, both for total and negative LN counts. For the T2b-3N2 subgroup, the hypothetical baseline 3-year survival (based on the y-intercept, i.e. 0 LNs examined) was 10%; similarly, for the T2b-3N3 subgroup, the baseline 3-year survival (also with an assumed 0 LNs examined) was 2% (Table 5Go). For all patients combined, the calculated 3-year survival rate at baseline was 7%. For every ten extra LNs added to the total LN count, the calculated overall survival increased by: 5.7% (T2b-3N2), 4.6% (T2b-3N3), or 5.9% (entire cohort). Despite the small incremental increases in survival, benefits based on increasing LN counts were obvious for all groups analyzed, but reached statistically significant differences only for the N3 subgroup. Figure 8Go represents a graphic display of this calculated numeric LN count effect on 3-year survival. Negative LN counts were analyzed in a similar fashion. For the entire cohort, the projected survival impact at 3 years of every ten negative LNs identified above a zero baseline count was 6% above a 13% 3-year survival (Table 6Go). For patients with N2 disease, this gain was calculated as 6.1% above a 15% survival, and for individuals with N3 categories, the increase was 4.8% above a 6% baseline survival. In this setting, the model showed a statistically significant survival enhancement based on increasing negative LN numbers only for patients with T2b-3N3 cancers. The resulting projected survival curve is depicted in Fig. 9Go.


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  		TABLE 5. Projected numeric total lymph node (LN) impact on 5-year overall survival
 

Figure 8
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  		FIG. 8. Plots of actuarial overall survival at 3 years versus the total number of lymph nodes examined, by stage group. A, T2b-3N2; B, T2b-3N3. The shaded area represents the 95% confidence intervals.

 

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  		TABLE 6. Projected numeric negative lymph node (LN) impact on 3-year overall survival
 

Figure 9
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  		FIG. 9. Plots of actuarial overall survival at 3 years versus the number of negative lymph nodes identified, by stage group. A, T2b-3N2; B, T2b-3N3. The shaded area represents the 95% confidence intervals.

 
Early postoperative deaths based on LN numbers
Among the entire cohort, there were 62 deaths (5%) within 1 month of diagnosis and 163 deaths (12%) within 3 months of diagnosis. There were no statistically significant differences between T2b and T3 patients with respect to deaths within 1 or 3 months (P = 0.4551 and P = 0.0978, respectively). Similarly, there were no obvious differences in 1- or 3-month mortality rates when we compared N2 and N3 patients (P = 0.26 and P = 0.60, respectively).

Early mortality was analyzed by the number of LNs resected, choosing total LNs categories as used in Table 2Go. For T2b patients, there was no statistically significant difference between LN count categories at 1 month (P = 0.0812) but there was a difference at 3 months (P = 0.0022). For T3 patients, similar analyses yielded P = 0.0671 at 1 month, and P = 0.4841 at 3 months. Mortality at 3 months in the T2b group was greater in those individuals with fewer LNs resected. For T2b patients who had between 7 and 9 LNs resected, the proportion of those who were dead at 3 months was 18% (17/96). Three-month mortality rates for T2b patients in the other LN count categories were: 10–15 LNs: 37/301 (12%); 16–19 LNs: 22/152 (14%); 20–24 LNs: 7/139 (5%); 25–29 LNs: 6/74 (8%); 30–39 LNs: 1/60 (2%); and 40 or more LNs: 2/46 (4%), respectively.

Stage migration
To test for the effect of stage migration and the number of LNs examined, we performed logistic regressions with N stage category as the dependent variable, and the following variables as independent predictors: total LNs examined, number of positive LNs found, and number of negative LNs examined. The regression result showed a proportional increase in N stage category as the number of LNs examined increased (P < 0.0001). In a separate regression analysis, as the number of negative LNs increased, N stage category increased, too (P = 0.0439). Based on the results of our cut point analysis (see Table 3Go), significant survival differences with lower total LN count cutoff points were primarily observed for N2 patients (or the entire cohort), but not for the N3 subgroup, indicating an obvious stage migration effect for patients with N2, but not N3 disease.


   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
The findings demonstrate that even in transmural or serosa-positive gastric cancer with advanced nodal involvement, more extensive LN dissection and analysis influences survival. This extends our earlier observation that postgastrectomy survival of T1-3N0-1 gastric cancer is strongly dependent on numeric LN evaluation.17 While we consider this apparent benefit of larger LN numbers removed for gastric cancer survival to mostly reflect the beneficial therapeutic potential of ELND, nontherapeutic mechanisms that could account for this observation can by no means be excluded. The following is an attempt to highlight potential nontherapeutic and therapeutic explanations, and reach a practical conclusion.

Stage migration, due to inappropriate understaging of the disease, was suggested to be a dominant factor in early-stage gastric cancer survival, when fewer than 10–15 LNs are examined to assign a N category.4,5,23,24 Recommended LN counts that would minimize such effect range from 1025 over 158,26 to 25 LNs.11 The SEER data for N0 and N1 resected gastric cancer indicate the greatest cutoff effect at a LN count of ten, suggesting that stage migration for these nodal categories is most prevalent when increasing total LNs up to ten have been examined.17 We think that for the N2 stage subgroups this phenomenon still exists, perhaps of lesser relevance than for N0 or N1 categories, as total LN counts of 15 or less still would preclude a proper N3 assignment, and as the median LN counts for the N2 group are indeed lower than those for the N3 cohort. At least 50% of patients with an N2 assignment were found to have the recommended minimum of 15 LNs examined, in comparison with 22% of N0 and 28% of individuals with N1 disease.17 The only patient group for which stage migration can be expected to be minimal is that with a N3 category. Obviously, less extensive disease with lesser survival hazards may "migrate" into this category due to more extensive regional dissection, but no higher nodal category exists to which patients could be assigned when greater regional LN numbers are examined, and in contrast to metastatic extraregional nodes, overwhelming regional LN burden would not qualify for a M1 assignment.19 It is precisely for this reason that we elected to investigate any potential therapeutic survival impact of ELND in this patient group. The significantly superior survival results of N3 gastric cancer with more than 40 total LNs examined or more than 20 negative LNs obtained thus have to be explained by mechanisms which are most likely different from stage migration.

Higher LN counts in the gastrectomy specimen could be surrogates for other factors which themselves are linked to superior survival. High LN numbers may be found in generally healthier individuals, with better nutrition, immune response, or performance status. For example, the implications of obesity in terms of a greater challenge in identifying LNs within the operative specimen have been postulated before.27 LN counts may vary between patients of various ethnicities, as does comorbidity, stage, and survival.28 High LN counts could also reflect special practice patterns that may translate into better outcomes, such as ELND being more likely performed in high-volume centers, by high-volume surgeons, and possibly with experienced pathologists more likely to conduct a specimen examination of appropriate diligence.29,30 Furthermore, patients undergoing gastrectomy in high-volume centers could be selected differently, so that confounding factors with increased survival hazards may be underrepresented in the high LN count group. The trend towards lower 3-month postoperative mortality in T2b patients, as demonstrated in this analysis, could certainly point into that direction. Finally, the findings presented herein have to be taken with appropriate caution, as they are obtained through highly selected cases from a database which lacks complete information on some prognostic details, such as margin status (R classification) or other histopathologic parameters with prognostic implications (Lauren type, Borrmann class). The validity of any possible conclusions drawn from such analysis does not only carry limitations due to the inherent quality of the data collection process, but also reflects the general inferiority of a retrospective analysis in comparison with a prospectively randomized comparative clinical trial.

Despite these caveats, we believe that the results speak for a therapeutic benefit as a result of ELND, even in patients with more advanced yet resectable gastric cancer. Although the perceived benefit is small, it is represented as an increased median survival, and does translate into a long-term survival benefit of around 10%. This percentage appears to represent well the subset of patients theoretically benefiting from ELND: those who have obvious or occult metastases to LNs beyond the immediate perigastric distribution only, but without cancer progression mechanisms that lead to diffuse peritoneal or systemic relapse, and which limit survival irrespective of the effects of optimized locoregional control.6,7 The impact of negative LN numbers on survival in these stage groups also support a therapeutic effect of ELND. In both N2 and N3 categories, an obvious survival benefit was observed at total LN counts of at least ten above the number of positive nodes, extending into the optimal survival observed at negative LN counts of 20 or greater. This corroborates findings from a gastric cancer nomogram, which places due prognostic weight to negative LN numbers, in addition to positive LN counts, after R0 resection.31 Interestingly, this prognostic nomogram has been validated through data from the Dutch trial which itself failed to demonstrate an obvious survival benefit after D2 dissection of gastric cancer.32 From this R0 subset of the Dutch trial we know that the median number of positive LNs was 1, and that of negative LNs 21; only 27% of patients was assigned one out of stages IIIA, IIIB, or IV. Is the lack of survival differences after D2 dissection16 thus a function of limited numbers of patients who would be at risk for a regional-only recurrence, aside from the other factors related to postoperative mortality?13,14 For the Dutch trial, the observed long-term survival benefit of D2 dissections for patients in the N2 subgroup would support this assumption.33

Stage-based survival prediction of advanced gastric cancer without distant metastases depends on total LN number and number of negative LNs. The clinical implications of these findings have to be discussed in the context of routine quantitative LN examinations for staging of operative specimens, and cannot reflect possible alternate directions such as sentinel LN biopsies.34,35 In addition, our results cannot indicate whether ELND influences the possible choice of postoperative adjuvant therapy36 nor suggest implications of LN status after preoperative chemoradiation or chemotherapy. However, for the curative-intent gastrectomy of locoregionally advanced gastric cancer, retrieval and examination of larger numbers of LNs are suggested. This should include the quest to surgical pathologists for a meticulous examination of the LN dissection specimens. The recommended minimum goal of 15 LNs to satisfy current AJCC staging criteria appears insufficient in this context. Especially for N3 categories, the minimum goal theoretically should be set to at least ten LNs above the number of positive nodes. Practically, this would require at least 25 LNs as postulated before,11 although counts of 40 or more total LNs appear even yet superior. It is assumed that multinodal resections in this setting can function as an asset to multimodal therapeutic approaches for these patients, too. The mechanism remains uncertain, but is not limited to stage migration. As long as operative morbidity is not affected negatively, ELND during potentially curative gastrectomy is recommended even for advanced gastric cancer.

Received for publication August 11, 2006. Accepted for publication August 16, 2006.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

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