Postoperative hypoalbuminemia, albumin supplementation, and short-term complications after radical gastrectomy in elderly gastric cancer patients

Objective To examine the association between early postoperative hypoalbuminemia and complications within 30 days after radical gastrectomy in older patients with gastric cancer, and to further explore the association between postoperative albumin supplementation and short-term outcomes among patients who developed hypoalbuminemia. Methods This single-center retrospective cohort study included 378 elderly patients who underwent radical gastrectomy for gastric cancer at the First Hospital of Jilin University from January to December 2023. Patients were classified into a hypoalbuminemia group (<30 g/L) and a normal albumin group (>=30 g/L) according to the lowest serum albumin level within the first 7 postoperative days. The primary outcome was Clavien-Dindo grade >=3 complications within 30 days after surgery, and the secondary outcome was Clavien-Dindo grade >=2 complications and postoperative length of stay. Covariates in the main adjusted models were prespecified on the basis of clinical relevance. Firth penalized logistic regression was used for the primary outcome because of the limited number of events, whereas conventional logistic regression was used for Clavien–Dindo grade ≥2 complications. Postoperative nadir albumin was also examined as a continuous variable. Among patients with hypoalbuminemia, propensity score matching was used to explore the association between postoperative albumin supplementation and short-term outcomes. A POD1 landmark sensitivity analysis was additionally performed to reduce temporal overlap between postoperative albumin assessment and complication occurrence. Results Among the 378 patients, 246 were classified into the hypoalbuminemia group and 132 into the normal albumin group. The incidence of Clavien–Dindo grade ≥3 complications was higher in the hypoalbuminemia group than in the normal albumin group (15.9% vs. 2.3%, P < 0.001). After adjustment for age, body mass index, American Society of Anesthesiologists physical status, preoperative serum albumin, surgical approach, surgical method, intraoperative blood transfusion, and pathological TNM stage, postoperative hypoalbuminemia remained associated with Clavien–Dindo grade ≥3 complications (adjusted OR, 4.51; 95%CI, 1.55–17.54; P = 0.004). When postoperative nadir albumin was modeled continuously, each 5-g/L decrease was associated with an adjusted OR of 4.71 (95%CI, 2.43–9.51; P < 0.001). The incidence of Clavien–Dindo grade ≥2 complications was also higher in the hypoalbuminemia group (61.8% vs. 24.2%, P < 0.001). The corresponding adjusted ORs were 3.75 (95%CI, 2.16–6.62; P < 0.001) for the categorical model and 4.21 (95%CI, 2.54–7.21; P < 0.001) per 5-g/L decrease in postoperative nadir albumin. Postoperative length of stay was longer in the hypoalbuminemia group [6.0 (5.0–9.0) d vs. 5.0 (4.0–6.0) d, P < 0.001]. In the POD1 landmark sensitivity analysis, the associations were attenuated. Lower POD1 serum albumin remained associated with Clavien–Dindo grade ≥2 complications in both the categorical model (adjusted OR, 1.90; 95%CI, 1.09–3.34; P = 0.024) and the continuous model (adjusted OR per 5-g/L decrease, 2.08; 95%CI, 1.36–3.22; P < 0.001), whereas the associations with grade ≥3 complications were no longer statistically significant. After 1:1 propensity score matching, 154 patients with hypoalbuminemia were included, with 77 patients in each supplementation group. Conditional logistic regression accounting for the matched-pair structure showed an association between recorded postoperative albumin supplementation and Clavien–Dindo grade ≥2 complications (OR, 2.00; 95%CI, 1.12–3.58; P = 0.020). Conclusions Lower serum albumin levels during postoperative days 1–7 were associated with Clavien–Dindo grade ≥3 and grade ≥2 complications within 30 days after radical gastrectomy in older patients with gastric cancer. However, these associations were attenuated in the POD1 landmark sensitivity analysis, particularly for grade ≥3 complications, highlighting the potential influence of temporal overlap and reverse causation. Because the albumin assessment window overlapped with the complication surveillance period, the main findings should be interpreted as associations rather than evidence of temporal sequence or causality. Among patients with hypoalbuminemia, recorded postoperative albumin supplementation was not associated with a lower incidence of complications; this finding may have been influenced by confounding by indication, residual confounding, and reverse causation. Postoperative assessment should therefore consider surgical trauma, inflammatory response, volume status, and overall recovery rather than relying on a single serum albumin value.