Early decrease in postoperative serum albumin predicts severe complications in patients with colorectal cancer after curative laparoscopic surgery

This retrospective study protocol was approved by the Medical Institutional Ethics Committee of Jiangsu province. Eligible patients with primary CRC undergoing elective laparoscopic colectomy at the Department of General surgery, Taizhou People’s Hospital from July 2015 to July 2017 were included. The inclusion criteria were as follows: (1) adult patients aged over 18, (2) first pathologically diagnosed with primary CRC supported by operative and pathological results, and (3) patients who underwent a curative laparoscopic resection of primary tumors for the first time. The exclusion criteria were as follows: (1) with tumor metastasis found either pre-operatively or intra-operatively, (2) with emergency operation due to complications (bowel obstruction, perforation, etc.), (3) with neo-adjuvant treatment, (4) accompanied by other malignancies; (5) and with laparotomy or laparoscopic conversion to laparotomy.

The surgical procedures, including the extent of both colectomy and lymph node dissection, were conducted according to the Colorectal Cancer Treatment Guidelines [9]. All the enrolled patients received the same perioperative managements. The diet was not resumed until the patients passed flatus. No patients died within postoperative day (POD) 30 in this present study.

The baseline characteristics (age, gender, etc.), intraoperative data (duration of operation, intraoperative blood transfusion, etc.), and laboratory data (CRP, Alb, etc.) were obtained from the database for the analysis. The pathological classifications were evaluated following the guidance of the 7th edition of American Joint Committee on Cancer (AJCC) TNM Classification.

The primary outcome was the occurrence of postoperative complications within postoperative 30 days [10]. Postoperative severe complications were defined as grade III and IV according to the Clavien–Dindo classification [11]. Enrolled patients were initially grouped according to the presence of severe complications.

As reported by previous studies [12], the relative change of the serum Alb (∆Alb) was defined as (preoperative Alb − nadir Alb within POD2)/preoperative Alb × 100%. The relative changes of the hemoglobin (Hb) and hematocrit (Hct) were with the same definitions. The median ∆Alb level was accepted as the cutoff value for the discrimination of high versus low value [7].

Data were analyzed by the SPSS 23.0 (SPSS, Inc., IA, USA) and GraphPad Prism 5.0 (GraphPad Inc., CA, USA), and a p < 0.05 was considered statistically significant. Before the study, we performed a sample size estimation of 150 patients. According to our clinical experience and previously published reports [7], the estimated incidence of postoperative severe complications was used as a basis for the minimum sample size estimation. Categorical data are presented as a number with percentage, whereas quantitative data is presented as median (range) or mean ± standard error (SE) respectively. Mann–Whitney U test or Student t test was used for continuous variables analysis, whereas chi-square test or Fisher’s exact test was used for categorical variables analysis as appropriate. Only those potential risk factors (p < 0.05) on univariate analysis were enclosed into the final multivariate logistic regression analysis. Binary multivariate stepwise logistic regression model was used in this study. The continuous data used in the logistic model was divided into two groups (high vs low, using the median value as the cutoff value). The predictive value of ∆Alb for postoperative severe complications was evaluated by receiver operating characteristic (ROC) curve analysis.

Of 218 consecutive patients, 25 patients were excluded according to the exclusion criteria (6 tumor metastases found intra-operatively, 7 emergency operations, 4 with neo-adjuvant treatment, 3 laparoscopic conversions to laparotomy, and 5 lack of albumin values within postoperative 2 days), which is shown in Fig. 1. A total of 193 patients were finally included in the multivariate analysis dataset, of which 60.1% (116/193) were male patients, as shown in Table 1. Eventually, 38 patients had postoperative severe complications according to the Clavien–Dindo grade, with an incidence of 19.7%. Postoperative severe complications included 6 severe bleedings, 9 anastomotic leakages, 18 severe infections, 4 bowel obstructions, and 1 severe cardiopulmonary failure. The mean age and BMI of the total cohort were 53.4 years and 20.8 kg/m² respectively. Patients with severe complications had an older age than those without severe complications (52.5 ± 11.7 vs 57.2 ± 12.1, p = 0.029). Patients with the comorbidity of hypertension were at an increased risk of postoperative severe complications (p = 0.029). The history of previous abdominal surgery was also significantly associated with increased severe complications (p = 0.030). In addition, patients with severe complications had a longer duration of operation (p = 0.043) and more estimated intraoperative blood loss (p = 0.032). Those patients with perioperative blood transfusion were also frequent in the patients with severe complications (p = 0.026). No significant differences were found in gender, BMI, smoking habits, ASA class, tumor location, AJCC stage, intraoperative fluid utilization, number of lymph nodes resection, and time to first flatus between the patients with or without severe complications (all p > 0.05).

As summarized in Table 2, the patients with severe complications had a significantly higher ∆Alb value than those without severe complications (13.3 ± 2.9 vs 19.0 ± 3.5, p < 0.001). In addition, higher ∆Hb (p = 0.034) and peak CRP level within POD3 (p = 0.005) were also significantly associated with postoperative severe complications.

Subsequently, univariate and multivariate analyses were performed to investigate potential risk factors for postoperative severe complications. These nine potential risk factors mentioned above (Tables 1 and 2) were enclosed into the univariate analysis. Of the nine factors, five (duration of operation, perioperative blood transfusion, ∆Hb, ∆Alb, and peak CRP within POD3) were significantly associated with postoperative severe complications. In the final multivariate logistic regression analysis, ∆Alb was the only independent factor associated with postoperative severe complications (OR 1.66, 95%CI 1.18–2.33, p = 0.003, see Table 3).

The receiver operator characteristic (ROC) curve analysis was applied to establish the predictive power of ∆Alb for postoperative severe complications. As illustrated in Fig. 2, the area under the curve (AUC) of ∆Alb was 0.916, with the cutoff value of 17.3%. The sensitivity and specificity were 0.842 and 0.858, respectively (p < 0.001).