Characteristics of patients
The baseline characteristics of patients are shown in Table 1. There were 196 males and 53 females in the population. The median age of all enrolled patients is 64y, range 31-82y. The details of pathology outcome showed that most patients (72.3%) had pure adenocarcinoma, and the remaining patients had mixed adenocarcinoma with signet ring or mucinous. There were 165 patients with tumors diameters larger than 4cm, and 84 patients with tumor diameters less than or equal to 4cm. Among then, 127 patients had lymphovascular invasion, and 154 patients had perineuronal invasion. Pathological differentiation showed that only 2 patients were G1, G2 accounts for 36.9%, and G3 remain the largest part, accounting for 62.2%.
Among the dissected lymph nodes, 70 patients had no positive lymph nodes, and 32 patients with PNLNR greater than 1, and 147 with PNLNR less than 1. Accoding to TNM stage, there were 23 patients defined as stage I, 45 patients stage II, 94 patients stage III and 87 patients stage IV.
In terms of surgery, there were a total of 3 types of surgical approaches, including 73 cases of left thoracotomy surgery, 1 case of Ivor Lewis surgery, and 175 cases of Transhiatal surgery. Total gastrectomy was performed in 115 patients, and proximal gastrectomy was performed in 134 patients. During surgery, a small part of patients (n=18) received intraoperative blood transfusion. After surgery, 53.4% patients stayed in the hospital more than 10 days, and 46.6% patients stayed less than or equal to 10 days. Long hospital stay is mainly due to postoperative complications, postoperative nutritional status and several other reasons. As to adjuvant chemotherapy, there were 100 patients received adjuvant chemotherapy, and the main chemotherapy regimens were SOX (S-1 and oxaliplatin) and XELOX (capitabin and oxaliplatin).
Survival data and prognostic factors
We conducted our last follow-up in October 2019 by telephone, outpatient or inpatient department visit. The median follow-up time was about 75 months. At the last follow-up, 111 patients are still alive. 1-year, 3-year and 5-year survival rate of all enrolled patients were72%, 59%, and 49%, respectively. The median survival time (mOS) of these patients was 70.1 months (95% CI 53.6-86.6m). Female patients had significant longer survival time than male patients (NA vs. 62.4m). Patients with pure adenocarcinoma had significant longer survival time than mixed pathology patients (85.4 vs. 42.5m). Patients with perineuronal invasion (NA vs. 48.1) or lymphovascular invasion (NA vs. 40.9) had shorter survival time. received blood transfusion (12.4 vs. 81.8) had shorter survival time (Figure 1). Patients received adjuvant chemotherapy (61.7 vs. 93.4) had longer survival time. The median survival time of no lymph node metastasis patients had not reached, while the median survival time of N2 and N3 patients was 64.5m and 24.0m, respectively. As to PNLNR, the mOS of patients with PNLNR≤ 1 was 10.3m, and patients with PNLNR>1 was 1.9m (Figure 2). The mOS of patients whose tumor size more than 4cm had also unreached, while mOS of those tumor size less than or equal to 4cm was 43.8m (Figure 3). pTNM stage was also significant related to survival time. Patients with elevated CA199, CEA, CA242 and AFP had shorter survival time (Table 2). Only 1 of 249 patients died within 30 days after surgery .
Prognostic factors including age, gender, pathology, tumor size, type of surgical approach, serum tumor biomarkers, and blood transfusion. Both univariate and multivariate analyses were applied (Table 2 and Table 3). Among the factors related to survival in univariate analyses, there were 16 factors had significant statistical differences, including gender, pathology, intraoperative blood transfusion, surgical approaches selection, and several serum tumor biomarkers. While factors including type of gastric resection, tumor differentiation, elevated serum AFP and serum ferritin had no significant differences. Then, the multivariate analysis was conducted to identify the predictive indicators for a good prognosis using the parameters which P value less than 0.5 by the univariate analysis. Multivariate analysis showed that intraoperative blood transfusion, tumor size more than 4cm, no adjuvant chemotherapy, higher positive/negative lymph node rate, perineuronal invasion and elevated serum CEA before surgery, stay more than 10 days in hospital after surgery are independent risk factors in resected Siewert type II AEG patients.