Huang CM, Lin BJ, Lu HS, Zhang XF, Li P, Xie JW. Effect of lymphadenectomy extent on advanced gastric cancer located in the cardia and fundus. World J Gastroenterol 2008; 14(26): 4216-4221 [PMID: 18636669 DOI: 10.3748/wjg.14.4216]
Corresponding Author of This Article
Chang-Ming Huang, Department of Oncology, Affiliated Union Hospital, Fujian Medical University, Xinquan Road No. 29, Fuzhou 350001, Fujian Province, China. hcmlr253@sohu.com
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Chang-Ming Huang, Bi-Juan Lin, Hui-Shan Lu, Xiang-Fu Zhang, Ping Li, Jian-Wei Xie, Department of Oncology, Affiliated Union Hospital of Fujian Medical University, Fuzhou 350001, Fujian Province, China
ORCID number: $[AuthorORCIDs]
Author contributions: Huang CM and Lin BJ conceived the study, analyzed the data, and wrote the draft of the manuscript and submitted the manuscript; Lu HS and Zhang XF helped revise the manuscript critically for important intellectual content; Li P and Xie JW helped collect data and design the study.
Correspondence to: Chang-Ming Huang, Department of Oncology, Affiliated Union Hospital, Fujian Medical University, Xinquan Road No. 29, Fuzhou 350001, Fujian Province, China. hcmlr253@sohu.com
Telephone: +86-591-87118266
Fax: +86-591-83320319
Received: April 23, 2008 Revised: May 16, 2008 Accepted: May 23, 2008 Published online: July 14, 2008
Abstract
AIM: To analyze the prognostic impact of lymphade-nectomy extent in advanced gastric cancer located in the cardia and fundus.
METHODS: Two hundred and thirty-six patients with advanced gastric cancer located in the cardia and fundus who underwent D2 curative resection were analyzed retrospectively. Relationships between the numbers of lymph nodes (LNs) dissected and survival was analyzed among different clinical stage subgroups.
RESULTS: The 5-year overall survival rate of the entire cohort was 37.5%. Multivariate prognostic variables were total LNs dissected (P < 0.0001; or number of negative LNs examined, P < 0.0001), number of positive LNs (P < 0.0001), T category (P < 0.0001) and tumor size (P = 0.015). The greatest survival differences were observed at cutoff values of 20 LNs resected for stage II (P = 0.0136), 25 for stage III(P < 0.0001), 30 for stage IV (P = 0.0002), and 15 for all patients (P = 0.0024). Based on the statistically assumed linearity as best fit, linear regression showed a significant survival enhancement based on increasing negative LNs for patients of stages III (P = 0.013) and IV (P = 0.035).
CONCLUSION: To improve the long-term survival of patients with advanced gastric cancer located in the cardia and fundus, removing at least 20 LNs for stage II, 25 LNs for stage III, and 30 LNs for stage IVpatients during D2 radical dissection is recommended.
Citation: Huang CM, Lin BJ, Lu HS, Zhang XF, Li P, Xie JW. Effect of lymphadenectomy extent on advanced gastric cancer located in the cardia and fundus. World J Gastroenterol 2008; 14(26): 4216-4221
At present, surgery is the most effective treatment for gastric cancer. As the standard procedure for advanced gastric cancer, D2 radical resection has been widely accepted and practiced[1–3]. The final results of a randomized Dutch trial[4] showed that patients with N2 disease might benefit from a D2 dissection, which required removing all the lymph nodes (LNs) of Group 1 and Group 2. According to another randomized Italian trial[5], a D2 lymphadenectomy was also advised. Lymph node metastasis is considered one of the most important prognostic factors[67], and adequate lymphadenectomy is advocated for gastric cancer. However, the number of LNs that should be removed and examined when performing a D2 lymphadenectomy has not been determined for advanced gastric cancer located in the cardia and fundus[8]. Therefore, the aim of this retrospective study was to evaluate the relative contributions of both the number of total resected LNs and the number of negative LNs to the outcome of patients with advanced gastric cancer located in the cardia and fundus, and provide further evidence for rational lymphadenectomy.
MATERIALS AND METHODS
Materials
Between January, 1996 and June, 2002, 236 patients diagnosed with primary gastric cancer located in the cardia and fundus was treated with curative resection at the Department of Oncology, Affiliated Union Hospital of Fujian Medical University, Fuzhou, China. The surgical procedure was defined as curative when no grossly visible tumor tissue (metastasis or LN involvement) remained after the resection and the resection margins were histologically normal. There were 197 male and 39 female patients whose ages ranged from 30 to 79 years (58.8 ± 9.8 years). All patients received a D2 or more extended dissection according to the Japanese Classification of Gastric Carcinoma (JCGC). Lymph nodes were meticulously dissected from the en bloc specimens, and the classification of the dissected LNs was determined by specialist surgeons who reviewed the excised specimens after surgery based on the Japanese Classification of Gastric Carcinoma[9]. The clinical and histopathologic data of each patient were collected and recorded in a specifically designed form. The tumors were histologically classified according to the WHO classification criteria and staged according to the 5th Edition of the TNM system[10], as listed in Table 1. The follow-up was carried out by trained investigators through mailings, telephone calls, visiting patients or recording the patients’ consultations at the outpatient service. The survival time was the time from diagnosis until the last contact, the date of death, or the date that the survival information was collected. All surviving patients were followed for more than five years. The median follow up for the entire cohort was 44 mo (range, 1-136 mo). The follow-up rate was 94.0%, with 222 cases involved.
Table 1 Clinical characteristics of the 236 patients.
Characteristics
n
Percentage
Gender
Male
197
83.5
Female
39
16.5
Age (yr)
< 60
103
43.6
≥ 60
133
56.4
Tumor size (cm)
< 3
88
37.3
3-6
97
41.1
> 6
51
21.6
Borrmann’s type
Type I, II
172
72.9
Type III, IV
64
27.1
Histological classification
Papillary adenocarcinomas
47
20
Tubular adenocarcinomas
101
42.8
Mucinous adenocarcinomas
29
12.3
Poorly differentiated adenocarcinomas
36
15.3
Undifferentiated carcinomas
8
3.4
Others
15
6.4
Depth of invasion (T category)
Muscularis (pT2)
25
10.6
Serosa (pT3)
118
50
Invasion to adjacent organs (pT4)
93
39.4
Lymph node involvement (N category)
pN0
42
17.8
pN1
97
41.1
pN2
68
28.8
pN3
29
12.3
Stage
II
48
20.3
III
128
54.2
IV
60
25.4
Type of gastrectomy
TG
190
80.5
PSG
46
19.5
Methods
Patients were stratified into five groups based on the number of total LNs removed as follows: < 15 LNs (36 cases), 15-19 LNs (43 cases), 20-24 LNs (62 cases), 25-29 LNs (40 cases) and ≥ 30 LNs (55 cases). Meanwhile, four groups were established based on the number of negative LNs as follows: 0-9 LNs (61 cases), 10-19 LNs (93 cases), 20-29 LNs (63 cases) and ≥ 30 LNs (19 cases). All calculations were performed using the SPSS 11.5 statistical package. Actuarial survival was determined via the Kaplan-Meier method, with univariate comparisons between groups through the log-rank test. Cox regression was used for multivariate analysis, with a backward elimination model for all covariates. A regression model to correlate negative 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. Significance of differences was assumed at P values less than 0.05 for all analyses.
RESULTS
Analysis based on total and negative LNs examined
Overall, 82.2% of patients (194/236) had LN metastasis. The incidences of LN metastasis were 56% for T2, 78.8% for T3 and 93.5% for T4. A total of 5615 LNs were picked up for histological examination, with 4005 being negative. The median of total LN number was 23 (range, 7-74; mean 23.8 ± 8.8) per patient, and the median of negative LNs was 16 (range, 0-48; mean 16.9 ± 9.3) per patient. There were no differences between T subcategories regarding total LNs resected [median (range): T2, 22 (9-31); T3, 26 (7-47); T4, 23 (7-74); Kruskal-Wallis, P = 0.062] or negative LN counts [median (range): T2, 12 (9-28); T3, 21 (1-45); T4, 17 (1-48); Kruskal-Wallis, P = 0.502].
Multivariate survival analysis
The five-year overall survival rate of the entire cohort was 37.5%. The backwards elimination model yielded the following independent prognostic variables: total LN count (or number of negative LNs examined; P < 0.0001), number of positive LNs (P < 0.0001), T category (P < 0.0001) and tumor size (P = 0.015). The covariates gender (P = 0.052), age (P = 0.329), Borrmann type (P = 0.373), histological grade (P = 0.132), and type of gastrectomy (P = 0.093) all failed to retain significance levels in this model. The risk ratios and 95% confidence intervals are listed in Table 2. The number of negative LNs and the total number of LNs examined behaved interchangeably and maintained a similar significance level when substituted for each other. This suggests that the number of negative LN can reflect the extent of lymphadenectomy, as can the total number of LNs.
Table 2 Multiple stepwise regression analysis with the Cox proportional hazards model (n = 236).
Impact of total LN counts by univariate survival analysis
When five-year overall survival was compared by increasing total LN count, higher LN counts were generally associated with better survival (Figure 1A). Of the entire cohort, for the T4, N2 and N3 categories, the best survival outcomes were observed with total LN counts no less than 30. For the N1 category, the best survival outcomes were observed with total LN counts between 25 and 29, as shown in Table 3. When adjusted for the T category, the survival rate of the 25-29 LNs group was higher than that of the < 15 (χ2 = 13.41, P = 0.0002), 15-19 (χ2 = 7.06, P = 0.008) and 20-24 LNs groups (χ2 = 5.69, P = 0.017). The survival rate of the ≥ 30 LNs group was higher than that of the < 15 (χ2 = 7.03, P = 0.008), and the 15-19 LNs groups (χ2 = 4.91, P = 0.03). When adjusted for the N category, the survival rate of the 25-29 LNs group was higher than that of 15-19 (χ2 = 9.67, P = 0.002) and 20-24 LNs groups (χ2 = 5.68, P = 0.02); the survival rate of the ≥ 30 LNs group was higher than that of the 15-19 (χ2 = 6.56, P = 0.01) and 20-24 LNs groups (χ2 = 4.56, P = 0.03).
Figure 1 A: Five-year survival curve for all patients according to five total LN strata; B: Five-year survival curve for all patients according to four different negative LN strata.
Table 3 Five-year overall survival by stage subgroups and total number of LNs dissected.
< 15
15-19
20-24
25-29
≥30
P
n
OS (%)
n
OS (%)
n
OS (%)
n
OS (%)
n
OS (%)
pTcategory
T2
4
25.0
8
50.0
9
55.6
3
33.3
1
0
0.2612
T3
20
13.8
23
22.6
25
45.1
24
37.0
26
48.5
0.6093
T4
12
4.6
12
7.5
28
13.5
13
23.1
28
37.5
0.0015
pNcategory
N0
8
15.0
10
41.7
11
60.0
8
62.5
5
40.0
0.2487
N1
16
8.7
15
13.3
24
37.8
15
52.9
27
40.7
0.0005
N2
12
7.7
17
8.3
19
12.5
10
25.0
10
30.0
0.0034
N3
NA
1
0
8
0
7
0
13
7.6
0.0016
Total
36
19.4
43
25.0
62
37.4
40
45.0
55
38.2
0.0009
Cut point analysis of survival differences relating to total LNs dissected
In an attempt to identify the optimal total LN count cutoff, survival comparisons were made for all stage groups at increasing total LN counts between 7 and 35. The greatest discrepancies, as measured by the chi-square test, were stage dependent, and varied from the cutoff levels of 20 (stage II), 25 (stage III), and 30 (stage IV) to the cutoff level of 15 (entire cohort), as listed in Table 4.
Table 4 Overall survival by total LN count, each stagesubgroup cut point analysis.
Total LN count
Stage II
Stage III
Stage IV
Total
χ2
P
χ2
P
χ2
P
χ2
P
7-14 vs≥ 15
0.17
0.6842
20.04
< 0.0001
4.36
0.0369
9.23
0.0024
≤ 19 vs≥ 20
5.22
0.0136
18.46
< 0.0001
8.70
0.0032
2.15
0.0425
≤ 24 vs≥ 25
0.27
0.6051
22.05
< 0.0001
9.07
0.0026
6.49
0.0109
≤ 29 vs≥ 30
1.20
0.2726
8.70
0.0032
13.70
0.0002
5.89
0.0153
Impact of negative LN counts by univariate survival analysis
The five-year survival, based on categories, showed considerable variations with increasing counts of negative LNs. An obvious trend toward better survival results for higher negative LN counts was observed (Table 5). Figure 1B shows the overall survival curve for all patients according to different negative LN strata. When adjusted for T category, the survival rate of the 20-29 LNs group was higher than that of the 10-19 LNs group (χ2 = 10.51, P = 0.0012); when adjusted for N category, the survival rate of the 20-29 LNs group was higher than that of either the 0-9 (χ2 = 14.99, P = 0.0001) or the 10-19 LNs group (χ2 = 5.23, P = 0.02); the survival rate of the 10-19 LNs group was higher than that of the 0-9 LNs group (χ2 = 19.05, P < 0.0001).
Table 5 Overall five-year survival by stage subgroup and number of negative LNs.
0-9
10-19
20-29
≥30
Log-rank P value
n
OS (%)
n
OS (%)
n
OS (%)
n
OS (%)
pTcategory
T2
4
0
15
47.1
6
83.3
NA
0.4907
T3
23
6.7
46
38.2
37
51.4
12
58.3
< 0.0001
T4
35
3.6
32
12.0
20
40.0
6
16.7
< 0.0001
pNcategory
N0
1
0
19
65.8
18
66.7
4
40.0
0.0317
N1
12
15.2
37
24.5
34
47.1
14
42.9
0.0328
N2
30
5.1
28
22.4
9
33.3
1
0
0.0055
N3
18
0
9
11.1
2
50.0
NA
0.0114
Total
61
4.8
93
33.8
63
53.9
19
45.0
< 0.0001
Projected impact of negative LN counts on overall survival
Based on the statistical linearity regression, the impact of negative LN counts on overall survival was analyzed. For the stage II subgroup, the hypothetical baseline five-year survival (based on the y-intercept, i.e. no negative LN) was 39.6%. Similarly, for the stage III subgroup, the baseline five-year survival (with an assumed zero negative LNs) was 15.4%. For the stage IV subgroup, the baseline five-year survival (also with an assumed zero negative LNs) was 2.5%. For all patients, the calculated five-year survival rate at baseline was 11.2%. For every ten extra LNs added to the negative LN count, the calculated overall survival increased by 5.77% (stage II), 6.09% (stage III), 7.65% (stage IV) or 6.24% (the entire cohort). In this setting, the regression showed a statistically significant survival improvement based on increasing negative LN number only for patients with stages III (P = 0.013) and stages IV (P = 0.035). The results for stage II had no statistical significance (P = 0.195).
DISCUSSION
Over the last few decades, an increase in the incidence of upper third gastric cancer has been reported by many investigators around the world[11–13]. It is generally accepted that the prognosis of patients with this type of carcinoma is worse than for tumors in other parts of the stomach[1415]. The only potentially curative treatment for this disease is complete surgical resection, with an en bloc LN dissection. The D2 radical resection has been regarded as the standard surgical procedure for advanced gastric cancer[16]. Lymph node dissection during the D2 radical resection is not confined to the anatomical extent, but also to the number of LNs dissected. The current edition of the UICC staging manual recommends examining at least 15 LNs for adequate gastric cancer staging. However, is that adequate for advanced gastric cancer located in the cardia and fundus? It was reported that patients with advanced gastric cancer located in the cardia and fundus often showed a higher frequency of perigastric LNs and higher proportion of overall LN metastasis[17]. Koufuji et al[18] investigated 49 cases with an upper gastric cancer invading the esophagus who underwent surgical treatment. The incidences of LN metastasis were 0% for T1, 67% for T2, 81% for T3 and 80% for T4. Ichikura et al[19] retrospectively analyzed 65 cases with cardiac carcinoma and found that the incidences of LN metastasis were 68% for Siewert’s type II tumors, and 94% for Siewert’s type III tumors. In the present study, 82.2% of patients had LN metastasis. For these patients, it is better to determine the extent of lymphadenectomy according to the extent of LN metastases preoperatively or intraoperatively. However, this is difficult to achieve as there is lack of reliable measures for clinical diagnosis preoperatively and for comprehensive LN biopsy intraoperatively[2021]. If the LNs were not completely removed, the probability of residual tumor cells would increase, leading to poor prognosis. Therefore, some investigators advocated removing adequate LNs intraoperatively to avoid this situation[22–24]. However, it is not certain how many LNs need to be dissected in a D2 lymphadenectomy. Liu et al[25] showed, in 147 patients with adenocarcinoma of the stomach who had undergone gastrectomy with curative intent, that for stage III disease, removal of >15 LNs appeared to provide a considerable survival advantage, compared with removal of < 15 LNs. Another study favoring this opinion was from Barbour et al[26]. They suggested that patients with Siewert type II and III adenocarcinoma of the gastroesophageal junction (GEJ) should undergo adequate lymphadenectomy to permit examination of ≥ 15 LNs, allowing accurate identification of prognostic variables. Removal of ≥15 LNs is associated with more accurate survival estimates for patients with advanced disease. For adenocarcinoma of the GEJ, a minimum removal of 25 LNs was recommended by Gee et al[27]. Our present observations showed that better long-term survival outcomes were obtained with higher numbers of LNs resected during D2 lymphadenectomy. This is consistent with the research results of Schwarz et al[28]. We suggest that for adequate LN resection, including total LNs and the number of negative LNs, the removal of 20 LNs for stage II, 25 LNs for stage III, 30 LNs for stage IV and 15 LNs for the entire cohort be recommended during D2 radical dissection.
Total LNs and number of negative LNs can reflect the extent of LN dissection and influence survival[2930]. In the present study, total LN count or negative LN counts turned out to be independent protective factors, according to the symbols of regression coefficient. These two factors behaved interchangeably, and maintained a similar significance level when substituted for each other. Furthermore, an impact of total LNs or negative LNs on survival was observed. In the univariate survival analysis, higher total LN counts may translate into better outcomes. The effect was much more significant with T4 and N2, N3 disease. We thus postulate that even in locally advanced disease with adjacent organ invasion or advanced nodal involvement that is still resectable, adequate LN dissection influences survival.
The contribution of negative LN counts to the prognosis of patients is partly due to LN microme-tastases. In patients without lymph metastases identified by HE staining, about 20% had LN micrometastases[31]. del Casar et al[32] reviewed 144 patients with primary gastric adenocarcinoma who underwent surgery and found that lymphatic and/or blood vessel tumoral invasion (LBVI) was present in 46 patients (31.9%), which was significantly associated with a poorer overall patients’ survival. Therefore, curability was reported as one of the most reliable predictors of long-term survival for LN-negative gastric carcinoma patients[33]. A similar study[34] examined the impact of the number of negative LNs on survival. The study was conducted in patients with stage III colon cancer, and demonstrated that a higher number of negative nodes was associated with better survival. In our study, the impact of negative LN on survival in these stage patients also showed an obvious trend toward better survival for higher negative LN counts. For every ten extra LNs added to the negative LN count, the calculated overall survival increased by 6.09% for stage III, and 7.65% for stage IV patients, based on the linear regression. Generally, better long term survival was observed with higher total LNs or negative LNs, showing the contribution of sufficient lymphadenectomy toward reducing residual tumor cells. For the curative-intent gastrectomy of locally advanced disease, retrieval and examination of adequate numbers of LNs is suggested for gastric cancer located in the cardia and fundus.
COMMENTS
Background
The incidence rates of upper third gastric cancer, mostly located in the cardia and fundus, has increased in recent years. Few studies have investigated the relative contributions of both the number of total resected lymph nodes (LNs) and the number of negative LNs to the outcome of patients with advanced gastric cancer located in the cardia and fundus.
Research frontiers
Some researches have considered D2 radical dissection to be standard procedure for advanced gastric cancer located the cardia and fundus, which requires the removal of Group 1 and Group 2 LNs. The dissected LN count is found to have strong association with patient survival.
Innovations and breakthroughs
The authors retrospectively reviewed 236 patients with gastric cancer in the cardia and fundus who were treated with D2 radical resection in a hospital in Fujian between 1996 and 2002 to investigate how the numbers of dissected LNs affect patients’ survival outcomes.
Applications
The authors suggest that importance should be attached to removing enough LNs so as to reduce residual tumor cells in patients with advanced gastric cancer located in the cardia and fundus.
Peer review
This article demonstrated that in advanced gastric cancer located in the cardia and fundus, the number of lymphadenectomy with/without metastasis of gastric cancer cells influenced the prognosis of the patients. This finding has important information for gastrointestinal surgeons.
Footnotes
Supported by (in part) The Follow-up Office established by the Department of Oncology, Affiliated Union Hospital of Fujian Medical University, Fujian Province, China
Volpe CM, Driscoll DL, Douglass HO Jr. Outcome of patients with proximal gastric cancer depends on extent of resection and number of resected lymph nodes.Ann Surg Oncol. 2000;7:139-144.
[PubMed] [DOI][Cited in This Article: ]
Di Martino N, Izzo G, Cosenza A, Vicenzo L, Monaco L, Torelli F, Basciotti A, Brillantino A, Marra A. [Total gastrectomy for gastric cancer: can the type of lymphadenectomy condition the long-term results?].Suppl Tumori. 2005;4:S84-S85.
[PubMed] [DOI][Cited in This Article: ]
Kulig J, Popiela T, Kolodziejczyk P, Sierzega M, Szczepanik A. Standard D2 versus extended D2 (D2+) lymphadenectomy for gastric cancer: an interim safety analysis of a multicenter, randomized, clinical trial.Am J Surg. 2007;193:10-15.
[PubMed] [DOI][Cited in This Article: ]
Hartgrink HH, van de Velde CJ, Putter H, Bonenkamp JJ, Klein Kranenbarg E, Songun I, Welvaart K, van Krieken JH, Meijer S, Plukker JT. Extended lymph node dissection for gastric cancer: who may benefit? Final results of the randomized Dutch gastric cancer group trial.J Clin Oncol. 2004;22:2069-2077.
[PubMed] [DOI][Cited in This Article: ]
Marubini E, Bozzetti F, Miceli R, Bonfanti G, Gennari L. Lymphadenectomy in gastric cancer: prognostic role and therapeutic implications.Eur J Surg Oncol. 2002;28:406-412.
[PubMed] [DOI][Cited in This Article: ]
Rodriguez Santiago JM, Munoz E, Marti M, Quintana S, Veloso E, Marco C. Metastatic lymph node ratio as a prognostic factor in gastric cancer.Eur J Surg Oncol. 2005;31:59-66.
[PubMed] [DOI][Cited in This Article: ]
Griffiths EA, Pritchard SA, Mapstone NP, Welch IM. Emerging aspects of oesophageal and gastro-oesophageal junction cancer histopathology - an update for the surgical oncologist.World J Surg Oncol. 2006;4:82.
[PubMed] [DOI][Cited in This Article: ]
Japanese Gastric Cancer Association. Japanese Classification of Gastric Carcinoma - 2nd English Edition -.Gastric Cancer. 1998;1:10-24.
[PubMed] [DOI][Cited in This Article: ]
Chien CR, Chen SW, Hsieh CY, Liang JA, Yang SN, Huang CY, Lin FJ. Retrospective comparison of the AJCC 5th edition classification for nasopharyngeal carcinoma with the AJCC 4th edition: an experience in Taiwan.Jpn J Clin Oncol. 2001;31:363-369.
[PubMed] [DOI][Cited in This Article: ]
Kubo A, Corley DA. Marked regional variation in adenocarcinomas of the esophagus and the gastric cardia in the United States.Cancer. 2002;95:2096-2102.
[PubMed] [DOI][Cited in This Article: ]
Cai L, Zheng ZL, Zhang ZF. Risk factors for the gastric cardia cancer: a case-control study in Fujian Province.World J Gastroenterol. 2003;9:214-218.
[PubMed] [DOI][Cited in This Article: ]
Mueller JD, Stein HJ, Oyang T, Natsugoe S, Feith M, Werner M, Rudiger Siewert J. Frequency and clinical impact of lymph node micrometastasis and tumor cell microinvolvement in patients with adenocarcinoma of the esophagogastric junction.Cancer. 2000;89:1874-1882.
[PubMed] [DOI][Cited in This Article: ]
Kim DY, Joo JK, Ryu SY, Park YK, Kim YJ, Kim SK. Clinicopathological characteristics and prognosis of carcinoma of the gastric cardia.Dig Surg. 2006;23:313-318.
[PubMed] [DOI][Cited in This Article: ]
Bruno L, Nesi G, Montinaro F, Carassale G, Lassig R, Boddi V, Bechi P, Cortesini C. Clinicopathologic findings and results of surgical treatment in cardiac adenocarcinoma.J Surg Oncol. 2000;74:33-35.
[PubMed] [DOI][Cited in This Article: ]
Degiuli M, Sasako M, Ponti A, Calvo F. Survival results of a multicentre phase II study to evaluate D2 gastrectomy for gastric cancer.Br J Cancer. 2004;90:1727-1732.
[PubMed] [DOI][Cited in This Article: ]
de Manzoni G, Morgagni P, Roviello F, Di Leo A, Saragoni L, Marrelli D, Guglielmi A, Carli A, Folli S, Cordiano C. Nodal abdominal spread in adenocarcinoma of the cardia. Results of a multicenter prospective study.Gastric Cancer. 1998;1:146-151.
[PubMed] [DOI][Cited in This Article: ]
Koufuji K, Shirouzu K, Aoyagi K, Yano S, Miyagi M, Imaizumi T, Takeda J. Surgery and clinicopathological features of gastric adenocarcinoma involving the esophago-gastric junction.Kurume Med J. 2005;52:73-79.
[PubMed] [DOI][Cited in This Article: ]
Ichikura T, Ogawa T, Kawabata T, Chochi K, Sugasawa H, Mochizuki H. Is adenocarcinoma of the gastric cardia a distinct entity independent of subcardial carcinoma?World J Surg. 2003;27:334-338.
[PubMed] [DOI][Cited in This Article: ]
Shimoyama S, Yasuda H, Hashimoto M, Tatsutomi Y, Aoki F, Mafune K, Kaminishi M. Accuracy of linear-array EUS for preoperative staging of gastric cardia cancer.Gastrointest Endosc. 2004;60:50-55.
[PubMed] [DOI][Cited in This Article: ]
Rasanen JV, Sihvo EI, Knuuti MJ, Minn HR, Luostarinen ME, Laippala P, Viljanen T, Salo JA. Prospective analysis of accuracy of positron emission tomography, computed tomography, and endoscopic ultrasonography in staging of adenocarcinoma of the esophagus and the esophagogastric junction.Ann Surg Oncol. 2003;10:954-960.
[PubMed] [DOI][Cited in This Article: ]
Baxter NN, Tuttle TM. Inadequacy of lymph node staging in gastric cancer patients: a population-based study.Ann Surg Oncol. 2005;12:981-987.
[PubMed] [DOI][Cited in This Article: ]
Bouvier AM, Haas O, Piard F, Roignot P, Bonithon-Kopp C, Faivre J. How many nodes must be examined to accurately stage gastric carcinomas? Results from a population based study.Cancer. 2002;94:2862-2866.
[PubMed] [DOI][Cited in This Article: ]
Saito H, Fukumoto Y, Osaki T, Fukuda K, Tatebe S, Tsujitani S, Ikeguchi M. Distinct recurrence pattern and outcome of adenocarcinoma of the gastric cardia in comparison with carcinoma of other regions of the stomach.World J Surg. 2006;30:1864-1869.
[PubMed] [DOI][Cited in This Article: ]
Liu KJ, Loewen M, Atten MJ, Millikan K, Tebbit C, Walter RJ. The survival of stage III gastric cancer patients is affected by the number of lymph nodes removed.Surgery. 2003;134:639-644; discussion 644-646.
[PubMed] [DOI][Cited in This Article: ]
Barbour AP, Rizk NP, Gonen M, Tang L, Bains MS, Rusch VW, Coit DG, Brennan MF. Lymphadenectomy for adenocarcinoma of the gastroesophageal junction (GEJ): impact of adequate staging on outcome.Ann Surg Oncol. 2007;14:306-316.
[PubMed] [DOI][Cited in This Article: ]
Schwarz RE, Smith DD. Clinical impact of lympha-denectomy extent in resectable gastric cancer of advanced stage.Ann Surg Oncol. 2007;14:317-328.
[PubMed] [DOI][Cited in This Article: ]
Smith DD, Schwarz RR, Schwarz RE. Impact of total lymph node count on staging and survival after gastrectomy for gastric cancer: data from a large US-population database.J Clin Oncol. 2005;23:7114-7124.
[PubMed] [DOI][Cited in This Article: ]
Lee HK, Yang HK, Kim WH, Lee KU, Choe KJ, Kim JP. Influence of the number of lymph nodes examined on staging of gastric cancer.Br J Surg. 2001;88:1408-1412.
[PubMed] [DOI][Cited in This Article: ]
Wu ZY, Li JH, Zhan WH, He YL, Wan J. Effect of lymph node micrometastases on prognosis of gastric carcinoma.World J Gastroenterol. 2007;13:4122-4125.
[PubMed] [DOI][Cited in This Article: ]
del Casar JM, Corte MD, Alvarez A, Garcia I, Bongera M, Gonzalez LO, Garcia-Muniz JL, Allende MT, Astudillo A, Vizoso FJ. Lymphatic and/or blood vessel invasion in gastric cancer: relationship with clinicopathological parameters, biological factors and prognostic significance.J Cancer Res Clin Oncol. 2008;134:153-161.
[PubMed] [DOI][Cited in This Article: ]
Kim DY, Seo KW, Joo JK, Park YK, Ryu SY, Kim HR, Kim YJ, Kim SK. Prognostic factors in patients with node-negative gastric carcinoma: a comparison with node-positive gastric carcinoma.World J Gastroenterol. 2006;12:1182-1186.
[PubMed] [DOI][Cited in This Article: ]
Johnson PM, Porter GA, Ricciardi R, Baxter NN. Increasing negative lymph node count is independently associated with improved long-term survival in stage IIIB and IIIC colon cancer.J Clin Oncol. 2006;24:3570-3575.
[PubMed] [DOI][Cited in This Article: ]
