Gastric cancer (GC) is one of the most prevalent death-related cancers all over the world. Surgical resection combined with lymphadenectomy is a pivotal treatment for GC patients. From 1997 to 2002, the International Union Against Cancer (UICC) and the American Joint Committee on Cancer (AJCC) have established the lymph node (LN) classification of GC, which is mainly based on the number of metastatic lymph nodes (LNs) [
According to the 7th edition of UICC/AJCC TNM system, regardless of total number of excised LNs, N0 classification is defined as the negative LNs metastasis [
To obtain a reliable assessment of N classification for GC patients, the UICC/AJCC recommends that at least 15 LNs should be dissected during surgery, irrespective of LN location [
From August 1995 to January 2011, a total of 300 patients who had curable gastric cancer and underwent radical gastrectomy at our single center were retrospectively reviewed. Inclusion criteria were listed as follows. (1) Primary adenocarcinoma was confirmed histopathologically. (2) No lymph node or distant metastasis (any T stage, N0, and M0) was reported in final pathological diagnosis. (3) No history of gastrectomy or other malignancies was detected via reviewing medical records. Patients who suffered from advanced gastric cancer would receive additional chemotherapy prior to surgery, with alkylating drugs and fluorouracil as main chemotherapeutic agents. The clinicopathological characteristics of all patients were collected from our medical database. The protocol of current study was approved by the Research Ethics Committee of Sun Yat-sen University, with informed consent obtained from all patients or their legal representatives.
All patients who underwent radical gastrectomy plus D2 lymphadenectomy were included in final analysis. A curative tumor resection was defined as macroscopic removal of all visible tumors and metastatic LNs, with pathologically negative resection margins of 6–8 cm (R0 resection) achieved. Subtotal (proximal or distal) or total gastrectomy was selected according to the individual condition during surgery. Billroth I reconstruction was performed after a proximal gastrectomy, while Billroth II fashion was applied after a distal gastrectomy. Roux-en-Y anastomosis between esophagus and small intestine was applied after a total gastrectomy.
Primary tumors were resected en bloc with D2 lymphadenectomy according to the Japanese Gastric Cancer Association guidelines. D2 lymphadenectomy involves the removal of all LNs in N1 and N2 stations. The perigastric LNs near lesser curvature (stations 1, 3, and 5) and greater curvature (stations 2, 4, and 6) were grouped together as N1 station. LNs near left gastric artery (station 7), common hepatic artery (station 8), celiac artery (station 9), and splenic artery (stations 10 and 11) were grouped together as N2 station.
If the LNs around spleen or splenic vessels were invaded by tumors, spleen would be excised, with an extra-vessel sheath lymphadenectomy performed meanwhile. All LNs were harvested immediately from the resected specimen by experienced surgeons, as the standard procedure [
According to the total number of dissected LNs, all patients can be artificially categorized into five groups: 1–15 LNs (
All patients had routinely been followed up after operation every 3 months for the first year, every 6 months for the second year, and twice a year thereafter. The routine examination during followup included a physical examination, blood chemistry, CXR, ultrasound of liver and abdomen, and bone scan the tumor marker levels. The follow-up period ranged from the first day of therapy until death or the last visit. The last following time in this study was January 2012. The survival time ranged from the first diagnosis of gastric cancer until the last contact after surgery, the date of death, or the date that the survival information was collected. In sum, nine patients were lost in the followup and the follow-up rate is 96%.
Data were expressed as mean ± SD if not indicating otherwise. The Kaplan-Meier method was used to investigate overall survival rate and potential prognostic factors. Factors associated with clinical outcomes were assessed by univariate analysis for quantitative variables and
A total of 300 patients (M : F, 16 : 1) were included in the final analysis, with average age of 56.3 (range: 26–81) years. Among this cohort, 7786 pieces of LNs were harvested during surgery (mean 26, range 10–91). The characteristics of enrolled subjects are shown in Table
Overall survival univariate analysis for predictive factors of survival.
Variables | Number, |
Survival, Mo |
|
|
---|---|---|---|---|
Gender | 0.912 | 0.364 | ||
Male | 205 (68.3%) |
|
||
Female | 95 (31.7%) |
|
||
Age (years) | 2.562 | 0.195 | ||
<60 | 172 (57.3%) |
|
||
≥60 | 128 (42.7%) |
|
||
Tumor Size (cm) | 0.352 | 0.624 | ||
<4 | 185 (61.7%) |
|
||
≥4 | 115 (38.3%) |
|
||
Tumor Location | 4.256 | 0.405 | ||
Upper third | 42 (14.0%) |
|
||
Middle third | 52 (17.3%) |
|
||
Lower third | 206 (68.7%) |
|
||
T Category | 41.012 | <0.001 | ||
T1 | 90 (30.0%) |
|
||
T2 | 55 (18.3%) |
|
||
T3 | 117 (39.0%) |
|
||
T4 | 38 (12.7%) |
|
||
Histopathological type | 15.375 | 0.079 | ||
Adenocarcinoma | 249 (83.0%) |
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||
Mucinous adenocarcinoma | 21 (7.0%) |
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||
Signet ring cell carcinoma | 30 (10.0%) |
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||
Histopathological grading | 25.654 | 0.125 | ||
Well/medicate differentiated | 199 (66.3%) |
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||
Poor/undifferentiated | 101 (33.7%) |
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Examined Lymph nodes, |
46.23 | <0.001 | ||
1–15 | 74 (24.7%) |
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||
16–20 | 53 (17.7%) |
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||
21–25 | 45 (15.0%) |
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||
26–30 | 36 (12.0%) |
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≥30 | 92 (30.6%) |
|
Data in survival present with median ± SD. Chi-square test was used to compare the categorical variables.
The clinical outcomes of all patients after surgery are shown in Table
Correlation between number of examined lymph nodes and clinical outcomes.
Variables | Overall | Number of examined lymph nodes |
|
|
||||
---|---|---|---|---|---|---|---|---|
1–15 | 16–20 | 21–25 | 26–30 | >30 | ||||
Hospital stay, day |
|
|
|
|
|
|
0.431 | 0.634 |
Transfusion volume, ML |
|
|
|
|
|
|
0.536 | 0.571 |
Operation time, min |
|
|
|
|
|
|
0.576 | 0.621 |
Postop. Complication, |
||||||||
No | 288 (96.0%) | 72 (97.3%) | 51 (96.2%) | 43 (95.6%) | 34 (94.4%) | 88 (95.7%) | 3.423 | 0.228 |
Yes | 12 (4.0%) | 2 (2.7%) | 2 (3.8%) | 2 (4.4%) | 2 (5.6%) | 4 (4.3%) |
Data present as mean ± SD without specific statement. Postop: postoperative; chi-square test was performed to compare differences.
The average overall survival time of GC patients was 50.2 ± 30.5 months. By Cox proportional hazard analysis, cancer-specific survival was significantly correlated with number of dissected LNs (
Prognostic factors retained in multivariate analysis.
Factors |
|
Relative risk | 95% CI |
---|---|---|---|
Invasion depth | <0.001 | 1.704 | 1.418–2.048 |
No. of examined lymph nodes | <0.001 | 1.616 | 1.468–1.779 |
Cox proportional hazard analysis was used to investigate the potential prognostic factors of survival in GC patients without lymph node metastasis.
During the follow-up period, 12 patients (4%) suffered from postoperative complications, with one case for pancreatitis, three for anastomotic fistula, five for intra-abdominal abscess, two for bowel obstruction, and one for intra-abdominal hemorrhage. According to linear regression analysis, no significant correlation was detected between examined LNs number and complication incidence (
To evaluate the relationship between survival time and dissected LNs number, subgroup analysis based on the T category was performed subsequently. For patients with T1 tumors, no significant correlation was found between the two factors. For patients beyond T1 stage, the number of dissected LNs was positively correlated to the overall survival time. However, this correlation was not observed when the number of examined LNs was more than 30 (Table
A stratified analysis between examined LNs and survival rate in all patients.
|
1–15 | 16–20 | 21–25 | 26–30 | >30 |
| ||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
|
ST |
|
ST |
|
ST |
|
ST |
|
ST | |||
T1 | 90 | 21 |
|
17 |
|
12 |
|
14 |
|
26 |
|
0.06 |
T2 | 55 | 10 |
|
13 |
|
8 |
|
6 |
|
18 |
|
0.002 |
T3 | 118 | 31 |
|
15 |
|
18 |
|
14 |
|
42 |
|
0.000 |
T4 | 37 | 12 |
|
8 |
|
9 |
|
2 |
|
6 |
|
0.000 |
|
||||||||||||
Sum | 300 | 74 |
|
53 |
|
45 |
|
36 |
|
92 |
|
0.000 |
ST: survival time (month for unit);
In the present study, the findings indicate that the GC-specific survival for patients without LN metastasis was significantly correlated with the depth of tumor invasion and the number of dissected LNs during surgery. By subgroup analysis, increased number of dissected LNs was found to be helpful in prolonging survival time in GC patients beyond T1 stage.
LN metastasis is one of the most crucial indicators of poor prognosis for patients with resectable gastric cancer. Furthermore, the location and total number of examined LNs are independent factors in predicting survival of patients with gastric cancer. Previous studies have shown that total number of examined LNs was associated with postoperative pathological grading and overall survival. Properly increasing the number of examined LNs during surgery could further improve the accuracy of pathological grading, which is helpful in prediction of survival for GC patients [
The UICC/AJCC TNM classification recommends that at least 15 LNs should be examined to accurately evaluate pathological N category of gastric cancer. Additionally, LN metastasis rate is recommended to be considered as a prognostic factor of gastric cancer [
It has been confirmed that LN-negative GC has similar clinicopathological features to early GC [
In this study, patients who had gastric cancer without LN metastasis and underwent curative operation were retrospectively reviewed. However, due to individual pathophysiological conditions and various surgeon’s preferences, there was a wide difference in dissected LNs number among all patients [
The prognostic predictive value of total LN dissected number in survival of LN-negative GC had been reported, but no common consensus has been reached yet. Actually, the core problem focused on determination of optimal number of examined LNs during operation. Bouvier’s study suggested that a reliable staging for LN-negative GC required at least 10 dissected LNs [
It has been proven that the total number of examined LNs is significantly related to the prognosis of patients with advanced gastric cancer [
In addition, the total number of examined LNs was also significantly related to the prognosis of early gastric cancer [
Several studies have suggested that postoperative complications were not correlated with the number of dissected LNs during surgery [
In conclusion, our results indicate that 26–30 of dissected LNs from resected tumors during standard gastrectomy with D2 lymphadenectomy could increase overall survival of LN-negative GC. Properly increasing the number of harvested LNs during surgery is a safe procedure and would not increase the incidence of postoperative complications.
All authors have declared no conflict of interests.
Wu Song and Yujie Yuan contributed equally to this study.