To find an accurate and simple predictor for postoperative short-term complications after gastrectomy.

Two hundred and twenty-three patients undergoing gastric cancer resection between October 1, 2015 and September 30, 2016 were enrolled in this study. Univariate and multivariate analyses were used to identify risk factors for complications after gastrectomy. The cutoff values and diagnostic accuracy were examined by receiver operating characteristic curves.

Sixty-two (27.8%) patients had short-term complications after gastric cancer resection. The postoperative decrease in serum albumin (∆ALB) was an independent risk factor for complications (OR = 17.957, 95%CI: 6.073-53.095, P < 0.001). The cutoff value was 14.0% and the area under the curve was higher than that of C-reactive protein on postoperative day 3 (area under the curve: 0.806 vs 0.709). Patients with ∆ALB ≥ 14.0% were more likely to have short-term complications after gastrectomy (46.7% vs 5.0%, P < 0.001), prolonged hospital stay (17.2 ± 10.8 d vs 14.1 ± 4.2 d, P = 0.007) and higher comprehensive complication index (P < 0.001) than those with ∆ALB < 14.0%.

Postoperative ∆ALB with a cutoff of 14.0% can be used to recognize patients who have high risk of short-term complications following gastric cancer resection.

Gastric cancer is one of the most common malignancies and is the third leading cause of cancer-related mortality in China. Surgery provides the only possibility of cure in patients with gastric cancer. Despite improvements in perioperative care and surgical procedures, postoperative complications remain a major impediment and threat to survival after gastric cancer surgery[1-3]. Therefore, it is crucial to specify a reliable and simple risk assessment index to indicate the possibility of postoperative complications, and the likelihood of early and safe patient discharge.

Many preoperative or postoperative indexes, such as C-reactive protein (CRP; a proinflammatory cytokine increasing in parallel with postoperative surgical stress), white blood cell count and albumin (ALB), have been identified as risk factors for complications after gastrectomy[4-8]. There are many studies revealing the association between serum ALB and postoperative outcomes. For example, preoperative hypoalbuminemia can predict surgical site infections[9]. Ryan et al[10] found that postoperative hypoalbuminemia on postoperative day (POD) 1 was associated with complications following esophagectomy. Sang et al[11] also found that hypoalbuminemia on POD 2 was an independent risk factor for acute kidney injury in patients with living donor liver transplantation. However, these studies mainly focused on the impact of serum ALB on nutritional status of patients[12,13].

ALB is also a negative acute phase protein and decreases after surgery, because of trauma and increased capillary leakage[14]. Norberg et al[15] observed an immediate and sharp decrease of serum ALB level (∆ALB) by 33% after major abdominal surgery, which occurred even earlier than the change in CRP. Unfortunately, few studies have identified the change in serum ALB level as a marker in predicting the outcomes of gastrectomy.

This study aimed to clarify whether the reduction of ALB level after surgery could be a predictor for short-term complications following gastric cancer resection. Therefore, the ∆ALB on POD 1 was examined and its diagnostic accuracy in gastric cancer was investigated.

In this study, serum ALB was mainly considered as an acute phase protein. The ∆ALB was an independent risk factor for prolonged hospital stay and complications after gastrectomy. Patients were distinguished as having low or high risk of complications after gastrectomy by the cutoff value of 14.0% in ∆ALB, which was more accurate than CRP level on POD 3.

Numerous studies have shown that preoperative and postoperative hypoalbuminemia are risk factors for complications after surgery[9-12], while few have specifically focused on the relationship between decreased serum ALB after surgery and clinical outcomes. Hübner et al[21] reported that stress response led to a reduction in postoperative albumin levels, which was consistent with the findings in our study. After major abdominal surgery, the albumin synthesis rate remained the same, whereas the fractional synthesis rate increased, leading to a decrease in plasma ALB[15]. However, sequestration into the interstitial space may contribute most to a postoperative drop in ALB level[14,21]. Capillary leakage is especially common in some malnourished patients with surgical trauma followed by an increased transcapillary escape rate of ≥ 100%[14,22,23]. To summarize, multiple factors affect the reduction in serum ALB after surgery and the stress response plays an important role in the change[23].

Nevertheless, increasing evidence shows that postoperative CRP level, as a risk factor for postoperative inflammation, can be used to predict complications after gastrectomy[7,24]. For instance, Kim et al[16] found that the CRP level on POD 4 was one of the most reliable predictors for complications following gastric cancer resection, when compared to many systematic inflammatory markers (white blood cells, neutrophils, platelet counts and CRP on POD 1). However, in previous studies, certain drawbacks were found by using postoperative CRP as a marker of complications after gastrectomy, which lacks accuracy in certain conditions[16,21,25]. Rettig et al[5] discovered that increased CRP levels after surgery were not early enough to identify patients at high risk for postoperative complications. In our study, ∆ALB was an independent predictive marker for complications after gastrectomy in multivariate analysis. The AUC of ∆ALB was larger than that of CRP on POD 3, suggesting ∆ALB was a better positive predictive marker. According to these findings, ∆ALB had a higher predictive value and tended to be more precise than CRP.

∆ALB could be more precise than CRP in predicting complications after gastrectomy because it is more accurate in reflecting the stress response after surgical trauma. As previously mentioned, the serum ALB level decreases earlier than CRP level after major abdominal surgery. The postoperative reduction in ALB level is associated with systemic inflammatory response syndrome, which leads to increased fractional synthesis and pathological capillary leakage of serum ALB[14]. Besides, serum ALB has a series of significant physiological functions, including free radical scavenging, maintenance of colloid osmotic pressure, change of capillary membrane permeability, and anticoagulant effects[26]. Hypoalbuminemia inhibits the innate immune response by promoting granuloma formation and reducing collagen synthesis. As a result, the systemic immune status is more sensitive to infection and other postoperative complications[27]. In contrast, CRP is involved in innate immunity as an early defense against infection, enhancing phagocytosis by macrophages and assisting complement binding to damaged cells or foreign matter[28]. From the above, the finding that ∆ALB could be more precise than CRP in predicting complications after gastrectomy is understandable, and serum ALB is a better predictor of both systemic inflammation and nutritional status.

However, it remains to be established whether ALB supplementation benefits patients with a large ∆ALB after gastrectomy. Golub et al[29] reported that routine ALB infusion was not beneficial to patients in the surgical intensive care unit. For patients with postoperative hypoalbuminemia, ALB infusion was deemed to be useless after major gastrointestinal surgery[30]. No studies have ever demonstrated the benefit for patients with preoperative hypoalbuminemia. Instead, exogenous ALB administration might increase risks of edema, extravasation of albumin, or other postoperative complications[31]. More intensive perioperative care might relieve an early ∆ALB following gastric cancer resection and improve patient outcomes by reducing postoperative generalized inflammation[9].

There were several limitations to the current study. First, it was a retrospective observational analysis, so the possibility of residual confounding factors could not be entirely excluded. Second, it was a single-center study and the outcome might have been influenced by the small number of patients enrolled and perioperative management strategies in our hospital. To verify the conclusions, multicenter prospective studies involving a large volume of data are needed. Third, whether the findings in our study could be applied to other operations, such as esophagectomy or liver resection, is not known for sure.

In conclusion, this study confirmed that a postoperative ∆ALB can predict short-term complications following gastric cancer resection. The ∆ALB could be more accurate than postoperative CRP in predicting complications after gastrectomy. Surgeons are warned of potential postoperative complications in patients whose serum ALB levels are reduced by > 14.0%.

The authors gratefully acknowledge all of the investigators for their contributions to the trial, and Dr. Xiao-Fei Shen from Nanjing University and Dr. Hua-Tong Liu from Australian National University, who provided medical writing assistance.