Gastric cancer is the fourth most common cancer in the world, and the second most common cause of cancer-related death, affecting approximately 736,000 people in 2008 [
The aim of this study was to clarify the differences in clinicopathological characteristics in patients with gastric cardia cancer with or without EGJ invasion and to investigate optimal clinical management of gastric cardia cancer.
We retrospectively studied patients who underwent curative surgery, including lymph node dissection, for gastric cardia and subcardial cancers at the Digestive Disease Center, Showa University Northern Yokohama Hospital between October 2001 and December 2010. Clinical and histological data and prognoses were determined based on medical records.
Patients who underwent curative surgery for gastric cardia or subcardial cancer were included in this study. Inclusion criteria were (i) presence of histologically proven carcinoma of the upper-third of the stomach; (ii) histologically solitary tumors; (iii) no prior treatment by endoscopic resection, chemotherapy, or radiation therapy. Exclusion criteria were (i) presence of synchronous or metachronous malignancy; (ii) presence of severe organ dysfunction. All disease was pathologically staged using the AJCC/UICC TNM Cancer Staging Manual (7th ed.). All patient data were approved for use by the institutional review board of Showa University Northern Yokohama Hospital. This study was registered with the University Hospital Medical Information Network in Japan, number UMIN000008774.
Any gastric cancer entered in the proximal 5 cm of the stomach with EGJ invasion is defined as esophageal cancer by the AJCC/UICC, whereas any cancer near the EGJ without EGJ invasion is defined as gastric cancer. Thus, we categorized tumors centered in the proximal 5 cm of the stomach into two types, according to presence of EGJ invasion. Categorization criteria were (i) any histological carcinoma centered in the stomach within 5 cm from EGJ, with EGJ invasion (type Ge); (ii) any histological carcinoma centered in the stomach within 5 cm from EGJ, without EGJ invasion (type G). Type Ge tumors were staged using both esophageal cancer and gastric cancer staging manuals.
Statistical analysis was performed using JMP Statistical Discovery 9.0.3 (SAS Institute, Cary, USA). Fisher’s exact test and
A total of 80 patients were eligible and studied. Median follow-up period of the surviving patients was 32.5 months. Clinicopathological characteristics of the patients are summarized in Table
Clinicopathological characteristics of patients (
Variable | Number of subject |
---|---|
Age (year, mean ± SD) | 67.6 ± 10.8 |
Sex | |
Male | 61 (76.3%) |
Female | 19 (23.7%) |
Pathological tumor size (mm, mean ± SD) | 46.8 ± 22.7 |
Macro type | |
Type 0 | 31 (38.8%) |
Type 1 | 4 (5.0%) |
Type 2 | 18 (22.5%) |
Type 3 | 22 (27.5%) |
Type 4 | 1 (1.3%) |
Type 5 | 4 (5.0%) |
Main histological type† | |
Differentiated | 48 (60.0%) |
Undifferentiated | 32 (40.0%) |
Distance between EGJ and tumor epicenter | |
≤20 mm | 21 (26.3%) |
>20 mm | 59 (73.8%) |
Esophageal invasion | |
Yes | 26 (32.5%) |
No | 54 (67.5%) |
Lymphatic invasion | |
L0 | 32 (40.0%) |
L1 | 48 (60.0%) |
Venous invasion | |
V0 | 32 (40.0%) |
V1 | 48 (60.0%) |
V2 | 0 |
Depth of tumor invasion | |
pT1 | 29 (36.3%) |
pT2 | 11 (13.8%) |
pT3 | 26 (32.5%) |
pT4 | 14 (17.5%) |
Lymph node metastasis | |
pN0 | 45 (56.3%) |
pN1 | 12 (15.0%) |
pN2 | 11 (13.8%) |
pN3 | 12 (15.0%) |
Distant metastasis | |
M0 | 65 (81.3%) |
M1 | 15 (18.8%) |
TNM stage | |
I | 32 (40.0%) |
II | 21 (26.3%) |
III | 12 (15.0%) |
IV | 15 (18.8%) |
Extent of gastrectomy | |
Proximal | 31 (38.8%) |
Total | 49 (61.3%) |
Surgical approach | |
Laparoscopic surgery | 30 (37.5%) |
Hand-assisted laparoscopic surgery | 17 (21.3%) |
Open surgery | 33 (41.3%) |
Splenectomy | |
No | 56 (70.0%) |
Yes | 24 (30.0%) |
Thoracotomy | |
No | 74 (92.5%) |
Yes | 6 (7.5%) |
Postoperative chemotherapy | |
No | 45 (56.3%) |
Yes | 35 (43.8%) |
†Differentiated: papillary carcinoma, well differentiated adenocarcinoma, moderately differentiated adenocarcinoma; Undifferentiated: poorly differentiated adenocarcinoma, signet-ring cell carcinoma, mucinous adenocarcinoma.
Comparison of clinicopathological characteristics between type Ge and G tumor groups are summarized in Table
Comparison of clinicopathological characteristics of patients with gastric cardia cancer with or without esophageal invasion.
Variable | With esophageal invasion ( |
Without esophageal invasion ( |
|
---|---|---|---|
Age (year, mean ± SD) | 65.3 ± 10.8 | 68.6 ± 10.8 | 0.271 |
Sex | 0.773 | ||
Male | 19 (73.1%) | 42 (77.8%) | |
Female | 7 (26.9%) | 12 (22.2%) | |
Pathological tumor size (mm, mean ± SD) | 61.9 ± 18.9 | 39.5 ± 20.8 | <0.001** |
Main histological type† | 0.811 | ||
Differentiated | 15 (57.7%) | 33 (61.1%) | |
Undifferentiated | 11 (42.3%) | 21 (38.9%) | |
Distance between EGJ and tumor epicenter | <0.001** | ||
≤20 mm | 15 (57.7%) | 6 (11.1%) | |
>20 mm | 11 (42.3%) | 48 (88.9%) | |
Lymphatic invasion | 0.003** | ||
L0 | 4 (15.4%) | 28 (51.9%) | |
L1 | 22 (84.6%) | 26 (48.2%) | |
Venous invasion | <0.001** | ||
V0 | 3 (11.5%) | 29 (53.7%) | |
V1 | 23 (88.5%) | 25 (46.3%) | |
Depth of tumor invasion | 0.028* | ||
pT1 | 4 (15.4%) | 25 (46.3%) | |
pT2 | 3 (11.5%) | 8 (14.8%) | |
pT3 | 13 (50.0%) | 13 (24.1%) | |
pT4 | 6 (23.1%) | 8 (14.8%) | |
Lymph node metastasis | 0.002** | ||
pN0 | 7 (26.9%) | 38 (70.4%) | |
pN1 | 6 (23.1%) | 6 (11.1%) | |
pN2 | 5 (19.2%) | 6 (11.1%) | |
pN3 | 8 (30.8%) | 4 (7.4%) | |
Distant metastasis | 0.010* | ||
M0 | 11 (42.3%) | 54 (100%) | |
M1 | 15 (57.7%) | 0 | |
TNM stage | <0.001** | ||
I | 3 (11.5%) | 29 (53.7%) | |
II | 6 (23.1%) | 15 (27.8%) | |
III | 2 (7.7%) | 10 (18.5%) | |
IV | 15 (57.7%) | 0 | |
Extent of gastrectomy | 0.150 | ||
Proximal | 7 (26.9%) | 24 (44.4%) | |
Total | 19 (73.1%) | 30 (55.6%) | |
Surgical approach | 0.037* | ||
Laparoscopic surgery | 6 (23.1%) | 24 (44.4%) | |
Hand-assisted laparoscopic surgery | 4 (15.4%) | 13 (24.1%) | |
Open surgery | 16 (61.5%) | 17 (31.5%) | |
Splenectomy | <0.001** | ||
No | 9 (34.6%) | 47 (87.0%) | |
Yes | 17 (65.4%) | 7 (13.0%) | |
Thoracotomy | 0.013* | ||
No | 21 (80.8%) | 53 (98.2%) | |
Yes | 5 (19.2%) | 1 (1.9%) | |
Postoperative chemotherapy | 0.002** | ||
No | 8 (30.8%) | 37 (68.5%) | |
Yes | 18 (69.2%) | 17 (31.5%) |
*
†Differentiated: papillary carcinoma, well differentiated adenocarcinoma, moderately differentiated adenocarcinoma; Undifferentiated: poorly differentiated adenocarcinoma, signet-ring cell carcinoma, mucinous adenocarcinoma.
Incidence of lymph node metastases is summarized in Table
Comparison of lymph node metastasis in patients with gastric cardia cancer, with or without esophageal invasion.
Variable | With esophageal invasion ( |
Without esophageal invasion ( |
|
---|---|---|---|
Overall | 19 (73.1%) | 16 (29.6%) | <0.001** |
Depth of tumor invasion | |||
pT1 | 2/4 (50.0%) | 0/15 | 0.035* |
pT2 | 2/3 (66.7%) | 4/8 (50.0%) | 0.576 |
pT3 | 9/13 (69.2%) | 7/13 (53.8%) | 0.344 |
pT4 | 6/6 (100%) | 5/8 (62.5%) | 0.154 |
Location of lymph node | |||
Cervical LN | 0 | 0 | — |
Mediastinal LN | 2 (7.7%) | 0 | 0.103 |
Perigastric LN | 17 (65.4%) | 15 (27.8%) | 0.002** |
Left paracardial | 8 (30.8%) | 3 (5.6%) | 0.004** |
Right paracardial | 10 (38.5%) | 6 (11.1%) | 0.006** |
Lesser curvature | 12 (46.2%) | 12 (22.2%) | 0.028* |
Greater curvature | 4 (15.4%) | 2 (3.7%) | 0.100 |
Suprapyloric | 0 | 1 (1.9%) | 0.675 |
Infrapyloric | 1 (3.8%) | 0 | 0.325 |
Left gastric artery | 4 (15.4%) | 7 (13.0%) | 0.508 |
LN at Celiac trunk | 1 (3.8%) | 2 (3.7%) | 0.698 |
LN along hepatic artery | 2 (7.7%) | 1 (1.9%) | 0.245 |
LN along splenic artery | 3 (11.5%) | 1 (1.9%) | 0.098 |
LN at splenic hilum | 3 (11.5%) | 0 | 0.032* |
*
Although the usual tumor location of type Ge tumors is in the stomach, AJCC/UICC Cancer Staging Manual defines type Ge tumors as esophageal cancer. We investigated discrepancies between disease stages by the AJCC/UICC TNM gastric cancer and esophageal cancer staging manual (7th ed.). The stage discrepancy was visualized in Figure
Staging comparison of gastric cardia cancer with esophageal invasion (
The 5-year overall survival rate was 57.3%. Twenty-five patients had recurrent diseases (peritoneum: 11; lymph nodes: 9; liver: 3; lung: 3; bone: 1; adrenal gland: 1; anastomosis: 1), and 24 patients died. Eighteen, 1, and 5 of 24 patients died of cancer, surgical complication, and other causes. Overall survival rates were compared between the patients with type G and Ge tumors. In patients with pT1–4 tumors, although not significantly, the type G tumor group had a higher survival rate (5-year overall survival rate, 64.9%) than the type Ge tumor group (5-year overall survival rate, 49.0%) (
(a) Overall survival rates were compared between the patients with type G and Ge tumors. In patients with pT1–4 tumors, although not significantly, the type G tumor group had a higher survival rate than the type Ge tumor group (
Overall survival
Overall survival compared with tumor types and TNM stage
The aim of this study was to clarify the clinicopathological differences between gastric cardia cancer with and without esophageal invasion. Gastric cardia cancers with esophageal and EGJ invasion have been treated as EGJC [
Siewert et al. argued that complete surgical resection and lymph node metastasis were independent prognostic factors in EGJC, and subtotal esophagectomy had less survival effectiveness for the patients with type II adenocarcinoma [
We studied any tumor centered in the proximal 5 cm of the stomach, and simply categorized them in 2 groups including types Ge and G according to the presence of EGJ invasion. Whereas there were significantly differences in patients background between type Ge and G tumor groups, type G tumor group showed some differences in clinicopathological characteristics. In lymph node metastasis, approximately 70% and 30% of the patients with type Ge and G tumors, respectively, had lymph node metastases in this study. Although no cervical lymph node metastasis was recognized in either tumor group, lower mediastinal lymph node metastasis was recognized in only the type Ge tumor group. Especially, there was significant difference of incidence of nodal metastasis in left paracardial, right paracardial, and lesser curvature lymph node between two tumor groups. To achieve complete resection, we should perform partial or total gastrectomy and lower esophagectomy with lower mediastinal and abdominal lymphadenectomy for the type Ge tumor. For type G tumor, it was not necessary to perform mediastinal lymphadenectomy because there was no mediastinal lymph node metastasis in the type G tumor group.
Because EGJ invasion generally occurs with tumor progression in gastric cancer, it is reasonable that type Ge tumors have deeper depth of invasion and more widespread nodal metastasis than type G tumors. Additionally, esophageal invasion could increase risk of mediastinal lymph node metastasis. Therefore, the survival rate of patients with type Ge tumor was inferior, but not significantly, to patients with type G tumor.
The AJCC/UICC TNM staging system for esophageal cancer defines nodal metastasis at perigastric lymph nodes (other than the left and right paracardial lymph nodes) as distant metastasis [
As clinicopathological characteristics and survival between type Ge and G tumor groups differ, it is appropriate to distinguish type Ge with type G tumor; however, it is unclear from this study that we should treat type Ge tumors as esophageal cancer, because this study analyzed too small number of the patients to clarify the validity.
Because the AJCC/UICC Cancer Staging Manual categorizes gastric cardia cancer with EGJ invasion as esophageal cancer, EGJ invasion is an important factor in diagnosis and treatment for gastric cardia cancer. We retrospectively studied patients who underwent curative surgery for gastric cardia and subcardial cancers to clarify the differences in clinicopathological characteristics and prognoses in patients with gastric cardia cancer with (type Ge) or without (type G) EGJ invasion. Among patients with pT1 tumor, those with type Ge tumor had significantly higher incidence of lymph node metastasis, whereas mediastinal lymph node metastases were seen in only 2 patients with type Ge tumors.
As patients with Ge tumors staged by either esophageal or gastric cancer staging manuals showed no significant difference in survival rates, it is adequate to distinguish type Ge from type G tumor because of their clinicopathological differences. Therefore, it seems that to regard type Ge tumor as esophageal cancer is adequate.
The authors declare that they have no conflict of interests.
H. Ito conceived and designed the study, collected clinical data, and performed the statistical analysis and interpretation of data. H. Inoue participated in the study design and performed interpretation of data. N. Odaka, H. Satodate, M. Suzuki, S. Mukai, Y. Takehara, and T. Omoto collected clinical data. SK participated in the study design and coordination. All authors read and approved the final manuscript.
The authors are extremely grateful to all the patients and to the clinical staff who cared for these patients. They also are thankful to Dr. Shigeharu Hamatani for his reliable pathological diagnoses.