Lymph node metastasis is one of the most important prognostic factors for AEG . In addition, AEG can cause LNM and hematogenous metastasis at an early stage. Hence, the long-term prognosis of AEG patients has been demonstrated to be poor . Radical surgery has been proposed as the effective treatment for AEG, including complete resection of lesions and lymph node dissection [19, 20]. However, Siewert II/III AEG is characterized by specific anatomical location and complex lymphatic drainage direction. Therefore, the correct evaluation of the lymph node metastasis can determine the extent of optimal lymph node dissection. The development of a reasonable treatment protocol is of great significance for improving the long-term prognosis in lymphatic metastasis patients with II/III AEG.
Certain studies have reported that the rates of mediastinal LNM are estimated from 5–25% [11, 13, 21, 22], whereas the recurrence rates of mediastinal LNM following surgery ranged from 0 to 11% [12, 21, 23, 24]. In the present study, Siewert II AEG was associated with celiac and thoracic lymph node metastasis. Metastasis to the celiac lymph nodes was noted, such as in the cases of No.1, 2, 7, 3, 11, 4, 8. In addition, the rate of mediastinal lymph nodes, such as that for No. 110 and No. 111, ranged from 3 to 7.1%. Particular attention has to be paid in order to perform both celiac and thoracic lymphadenectomy. However, in view of the low LNM rate of pyloric lymph nodes (NO.5 and No.6) , tumor resection may be considered for this type of patients. Yamashita et al further showed similar results in a previous retrospective study . Siewert III AEG patients did not present with mediastinal LNM and presented with tumor recurrence in the thoracic cavity. It should be noted that the mediastinal LND can increase surgical trauma and cardiopulmonary complication, notably in the elderly population . Therefore, mediastinal LND is not necessary for Siewert III AEG patients. However, No.5 and No.6 LNM rates were estimated to 10% and 16.7%, respectively. A previous study reported that the dissection of pyloric lymph nodes could improve long-term prognosis for Siewert III AEG [25, 28]. Therefore, this type of patients should be treated with dissection of the pyloric lymph nodes. Moreover, we should emphasize on the en-bloc resection and avoid fragmented resection .
The assessment of the risk of LNM can aid the selection of the appropriate extent of lymph node dissection and individualized treatment strategy. At present, there is no effective method to evaluate LNM prior to surgery. However, the clinicopathological data exert a favorable prediction effect. In the present study, the infiltration depth, gross type and intravascular cancer embolus were independent risk factors for lymph node metastasis in patients with Siewert II/III AEG. Previous studies have reported that the LNM rate was significantly increased following an increase in the tumor infiltration . The present study indicated similar outcomes demonstrating that the LNM rate was increased from 0 to 88.1% when the tumor infiltrated deeper gradually. This outcome may be attributed to the abundance of lymphatic capillaries in the submucosa, resulting in lymph node metastasis [31, 32]. In addition, whether the gross type is a risk factor for LNM remains a controversial issue. Several studies have demonstrated that the gross type was associated with LNM, while other reports have produced opposite results [31, 33, 34]. Moon et al reported that the gross type was not an independent risk factor for LNM . However, in the present study, the LNM rates of the depressed type (62.4%) and protruded type (18.2%) metastases were higher than those of the flat type (7.1%). The gross type was a risk factor for LNM, which was in accordance with the results of Choi et al . The present study indicated that although the gross type was not associated with LNM in the multivariate analysis, the opposite findings were noted in the univariate analysis . A similar Chinese study reported that the gross type was associated with metastasis and recurrence in the upper gastric cancer [37, 38]. Hence, the gross type may become a useful indicator for the prediction of LNM. However, we need to further verify these findings using large-sample data. In addition, among the 60 patients who were combined with intravascular cancer embolus, 45 patients exhibited LNM. The incidence was higher than those patients who did not present with intravascular cancer embolus. A previous study demonstrated that 54 gastric cancer patients with intravascular cancer embolus exhibited 51 cases with lymph node metastasis (94.4%) . This may be due to the capillary wall that does not contain a basal membrane and is composed of endothelial cells. The majority of these cells are irregularly arranged. Therefore, the capillary wall has greater permeability than the capillary and is more susceptible to cancer cell invasion . Nevertheless, since it is difficult to determine whether patients present with intravascular cancer embolus preoperatively, tumor infiltration depth and gross type remain valuable indicators for the prognosis of the disease.
In the present study, survival analysis revealed that LNM exhibited significant differences in the 3-year overall survival rate. The data indicated that patients with LNM exhibited worse long-term prognosis. It was reported that proximal gastric cancer could develop LNM and exhibit early recurrence . Kim et al revealed that the survival rate was decreased following an increase in the LNM rate . The data indicated that LNM was an independent prognostic risk factor for 86 patients . A study conducted in China revealed that the 3-year and 5-year survival rates of 231 gastric cancer patients without LNM were 69.7% and 63%, respectively, while the survival rates of 481 gastric cancer patients with LNM were 38.4% and 28.7%, respectively (P = 0.001). In addition, a multi-center study demonstrated that Siewert II AEG patients with mediastinal LNM exhibited a higher recurrence rate and a poor prognosis . As a result, LNM should be considered a prognostic evaluation index for gastric cancer patients who have received radical operation.
However, perioperative chemotherapy can improve the long-term prognosis of AEG patients to some extent. The current result was consistent with previous studies . The EORTC40954 clinical trial indicated that the preoperative chemotherapy combined with surgery could increase R0 resection but failed to show survival benefit in stage III and IV (cM0) of AEG or gastric cancer patients . In addition, the FNCLCC and FFCD9703 clinical trials revealed that perioperative chemotherapy could improve the curative surgical rate, the overall survival (OS) and the disease-free survival (DFS) . In 2011, the ACTS-GC trial reported that postoperative treatment with S-1 chemotherapy could prolong the 5-year OS and DFS . The CLASSIC study for stage II to stage IIB gastric cancer revealed that patients who received chemotherapy following surgery exhibited optimal prognosis than those treated with surgery alone . Recently, the POET trial compared chemotherapy and surgery with induction chemotherapy, chemoradiotherapy and surgery . The data demonstrated that induction chemotherapy and chemoradiotherapy could prolong progression-free survival (PFS) . Therefore, chemotherapy has become a necessary treatment modality in advanced AEG.
The present study exhibits certain limitations. It is a retrospective, single-center study, involving a small number of samples. Therefore, the results are unlikely to fully reflect the regulation of LNM and long-term prognosis. There may be certain bias in the analysis of the clinical data. Hence, we need to further confirm the current findings by large-sample, randomized controlled studies.