Prognostic Factors Affecting Survival After Curative Resection in Patients with pT4aN0M0 Gastric Cancer

Gastric cancer is still one of the most common tumors in the
world, although shows decreasing trends in its incidence in recent
years...


Introduction
Gastric cancer is still one of the most common tumors in the world, although shows decreasing trends in its incidence in recent years. Surgery is the main method to provide the opportunity for radical cure [1][2][3][4]. The presence of lymph node metastases and the depth of tumor invasion are most important predictors of postoperative outcome for gastric cancer patients without distant organ metastasis [5][6].For advanced gastric cancer, compared to those with nodal metastases, the patients with node-negative gastric cancer have better prognosis [7][8]. A significant positive correlation was found between T staging and N staging in gastric cancer patients. However, in some other cases, postoperative pathological results revealed nodal metastases still do not developed even when tumor cells invade the serosa [9][10]. For these patients, more attention should be paid on long-term survival and prognostic factors associated because of its unique biological characteristics. The aim of this investigation was to evaluate the long-term survival and prognostic factors associated with pT4a patients with node-negative gastric cancer who underwent curative resection.

Patients
The data of gastric cancer patients who underwent curative gastrostomy (R0 resection) in our hospital from December 2009 to June 2016 was retrospectively analyzed. The patients underwent D2 or D2+ lymph node dissection accordance with the Japanese Gastric Cancer Association Guidelines and postoperative pathological TNM staging diagnosed as pT4aN0M0 based on the seventh edition of the Union for International Cancer Control TNM Classification [11] were enrolled in this investigation. Exclusion criterias were as follows: (1) Patients with lymph node metastases and/ or distant metastases. (2) Patients underwent preoperative chemotherapy and/ or radiation therapy. (3) The number of lymph nodes dissection was less than 16. (4) Suffered from other synchronous primary tumors simultaneously. Lymph node metastasis status was pathological examined by routine method in this investigation.

Date Collection
This study was approved by the Regional Ethics Committee of our institution. We collected and analyzed the data of patients,

Statistical Analysis
All statistical analyses were performed by SPSS 15.0. Survival curves were analyzed by using the Kaplan-Meier method, and the differences between subgroups were compared by means of the log-rank test. The independent prognostic factors identified by multivariate analysis by performed using the Cox proportional hazard regression model with a forward stepwise procedure.
Values of p< 0.05 were considered to be statistically significant.

Characteristics of Patients
In total, clinicopathological data of 991 patients was analyzed and 84 patients were recruited to the study. The complete demographic details of 84 patients are summarized in (Table 1).

Short-Term Outcomes and Postoperative Complications
Totally, 6 patients (7.1%) developed postoperative complications which identified within 30 days after operation and 3 cases developed more than one type. There was one duodenal stump leakage, one gastro-jejun anastomotic leakage, 3 of intestinal obstruction, 2 of postoperative anastomotic bleeding and wound infection were observed in 4 cases. There was no death during hospitalization. Data are provided in Table 2.

Long-Term Outcomes and Prognostic Factors
The follow-up periods ranged from 14 to 81 months, and the  (Figures 1 &2).

Discussion
Although lymph node metastases are confirmed as one of the most significant predictors of postoperative outcome for gastric cancer patients, it does not suggest node-negative patients have no chance of recurrence [12][13][14].Researchers have reported that the depth of tumor invasion was an independent predictor related to the postoperative survival rate, which is independent of lymph node metastasis [15]. We also found that he higher serum level of CEA was a negative predictor, patients with lower levels preoperatively had a longer OS than those patients with higher levels. CEA is a glycoprotein with a weight of 200 kDa, which play an important role in programmed cell death adhesion in mammals. It is one of the most common tumor markers which is widely using in cancer diagnosis and treatment decision especially in gastrointestinal cancer [21][22][23]. However, the value of serum level of CEA for postoperative surveillance remains poorly understood. We revealed that a high preoperative serum CEA level was independently associated with a poor prognosis after radical gastrectomy in patients with no lymph node metastases.
This finding may reflect a widely accepted hypothesis that the long-term outcome of cancer patients is not determined by tumor characteristics alone, but also associated with cancer-related microenvironment.

Conclusion
Although this study had limitations, the investigation demonstrated that the higher serum level of CEA and the presence of lymphatic invasion were associated with an unfavorable OS for patients with pT4aN0M0 gastric cancer who underwent curative gastrostomy combined with D2 or D2+ lymph node dissection.
Such patients should be considered to provide individual follow-up and adjuvant therapy because of an increased risk of postoperative recurrence.