Our results showed that the postoperative GPS was an independent risk factor for poor prognosis in patients with GC. In addition, postoperative GPS is associated with advanced tumors, invasive surgery, and postoperative complications. To the best of our knowledge, this is the first report to demonstrate the impact of postoperative GPS in patients with GC and to compare this risk factor with other preoperative and postoperative systemic inflammatory response markers.
Systemic inflammatory response plays an important role in the development and progression of cancer. Until now, it has been reported that preoperative systemic inflammatory response markers are associated with the prognosis of GC [5, 6]. However, most studies have focused on preoperative conditions, and a few have examined the relationship between postoperative systemic inflammatory response and cancer survival. Takeno et al. showed that high-sensitivity inflammation-based GPS a month after surgery was an independent prognostic factor in patients with GC compared to GPS and modified GPS [7]. Miyatani et al. reported that the combination of the preoperative and postoperative NLR appears to be useful for predicting the prognosis of patients with GC [8]. Some reports indicate that the postoperative NLR in curative surgery for colorectal cancer or postoperative GPS in hepatectomy for colorectal liver metastases are independent prognostic factors [9, 14]. In the current study, using preoperative and postoperative prognostic markers, we identified the most suitable predictor and demonstrated that postoperative GPS was an independent risk factor for poor DFS and OS in patients with GC after gastrectomy. To the best of our knowledge, no other report has compared preoperative and postoperative multiple inflammatory response markers and prognosis; thus, these results are valuable.
GPS was first presented as a systemic inflammation response marker based on a combination of CRP and Alb levels in patients with inoperable non-small cell lung cancer [15]. Inflammatory cytokines, such as interleukin-1, interleukin-6, and tumor necrosis factor-α, have been reported to induce an increase in serum CRP levels [16]. Alb is the standard factor used to assess a patient’s nutritional status and decreases secondarily to a systemic inflammatory response. Inflammatory cytokines are known to be associated with tumor growth [17]. Therefore, GPS can function as a cytokine-mediated inflammatory response, as well as its role in prognosis [18, 19].
The postoperative systemic inflammatory response may be related to the influence of preoperative, intraoperative, and postoperative factors. Regarding preoperative factors, in the current study, there were significantly more patients with preoperative GPS 1 or 2 and advanced stage in the postoperative GPS 1 or 2 group. Given that the tumor was removed, it was unclear whether preoperative factors influenced the postoperative GPS. However, it has been reported that the half-life of Alb is 21 days and that intraoperative factors of advanced tumors may have affected the postoperative GPS [14]. In addition, even when the tumor is removed, the main cause of recurrence after surgery may be the growth of micrometastatic residual tumor cells that cannot be eradicated by surgery [20], and residual cancer cells may grow in response to postoperative inflammatory cytokine activity [21].
Regarding intraoperative factors, McSorley et al. showed a significant association between perioperative blood transfusion and postoperative systemic inflammatory response and survival following surgery for colorectal cancer [22]. In addition, an association between laparoscopic surgery and a lower postoperative systemic inflammatory response has been reported [22]. In the current study, patients who received blood transfusions and those who underwent laparotomy were significantly more common in the GPS 1 or 2 group. Blood transfusions and laparotomy may increase the postoperative systemic inflammatory response, as previously reported.
In terms of postoperative factors, Kubota et al. reported that postoperative complications affected DFS and OS among 1395 patients who underwent gastrectomy for GC [23]. Okumura reported that prolonged inflammation due to postoperative complications is associated with poor DFS and OS after resection for GC [24]. In the current study, postoperative complications were significantly more common in patients with a postoperative GPS of 1 or 2. This finding suggests that prolonged inflammation due to postoperative complications may contribute to the poor prognosis of patients with GC. Therefore, the poor prognosis of patients with postoperative GPS 1 or 2 in this study may be due to postoperative complications.
It remains unclear why an increased postoperative inflammatory response promotes recurrence and a poor prognosis in patients with GC. However, the present study revealed that preoperative, intraoperative, and postoperative factors were involved in the postoperative inflammatory response. Thus, surgeons can avoid postoperative systemic inflammatory responses and achieve a better prognosis for patients with GC through preoperative nutritional therapy, minimally invasive surgery, and avoidance of complications.
Our study has several limitations. This retrospective study was conducted at a single institution with a small number of cases. We assessed postoperative GPS one month after the operation; however, whether one month after surgery is an appropriate time to assess GPS for postoperative evaluation remains debatable. The selection between laparoscopic and open surgery is based on the judgment of the attending physician and is not standardized. A large prospective study is needed to confirm our findings.