ROC curve of the CONUT score, PNI, ALB, and PLR
Depend on the criteria of inclusion and exclusion in this study, 309 patients were enrolled finally. The ROC curves of the CONUT score, PNI, ALB, and PLR are depicted, and the areas under the curve (AUC) were 0.718, 0.694, 0.680, and 0.635, respectively. The CONUT score was the most useful predictor. The demarcated values of the CONUT score that correlated with outcomes differed from those in previous studies8, 14–19. In our study, the cut-off value in prediction of postoperative complications was identified as 2.5. The Youden index of the CONUT score was 0.343, with a sensitivity of 0.549 and specificity of 0.794. The positive predictive value for postoperative complications was 52.3% and the negative predictive value was 80.8%.
Study population and baseline characteristics based on the CONUT score cut-off value
According to the cut-off value of CONUT score, 214 patients with score less than 2.5 were in the low CONUT score group and 95 patients with score more than 2.5 were in the high CONUT score group. The average age of patients in the low CONUT score group was much lower than those in the high score group (62.2 ± 0.7 y vs 66.2 ± 1.2 y, P = 0.003). Comparison in the ratio of males to females in these two groups was no significant difference (155/59 vs 73/22, P = 0.416). The body mass index (BMI) was significantly lower in patients with a CONUT score > 2.5 than in those with a CONUT score < 2.5 (21.9 ± 0.3 kg/m2 vs 23.1 ± 0.2 kg/m2, P < 0.001). The rate of diabetes mellitus was significantly higher in the high CONUT score group (8.9% vs 20.0%, P = 0.006), however, no significant difference was found in hypertension (35.5% vs 43.2%, P = 0.201). The high CONUT score group experienced much more previous abdominal surgery (18.7% vs 31.6%, P = 0.013). There were 193 (62.5%) patients who received distal gastrectomy and 116 (37.5%) patients who received total gastrectomy, with no significant difference was found in patient with high and low score (131/83 vs 62/33, P = 0.498).
Comparison of clinical characteristics between patients with a low and high CONUT score
Compared to the low CONUT score group, the levels of preoperative haemoglobin (Hb) (132.5 ± 1.3 vs 104.5 ± 2.4, P < 0.001), ALB (40.9 ± 0.3 vs 34.6 ± 0.5, P < 0.001), red blood cells (RBCs) (4.38 ± 0.04 vs 3.60 ± 0.07, P < 0.001), platelets (PLTs) (221.4 ± 4.5 vs 206.5 ± 7.4, P < 0.001), total lymphocytes (1.79 ± 0.04 vs 1.04 ± 0.04, P < 0.001), and cholesterol (5.02 ± 0.07 vs 3.64 ± 0.08, P < 0.001) were lower and the C-reactive protein (CRP) level (3.2 ± 0.6 vs 9.6 ± 1.8, P < 0.001) was higher in the high CONUT score group. Regarding preoperative tumour biomarkers, there were significant differences in carbohydrate antigen 125 (CA125) (P = 0.001) and carbohydrate antigen 199 (CA199) (P = 0.016) but not in carcinoembryonic antigen (CEA) (P = 0.769) or alpha fetoprotein (AFP) (P = 0.487). Patients with low CONUT scores were more likely to have pathological stage I disease (37.4% vs 23.2%, P = 0.014), while patients with high CONUT scores were more likely to have stage III disease. The high CONUT score group suffered from significantly more postoperative complications (19.2% vs 52.6%, P < 0.001) and had a longer postoperative stay (11.6 ± 0.5 d vs 14.1 ± 0.7 d, P = 0.006) than the low CONUT score group. More details are shown in Table 2.
Table 2
Study population and baseline characteristics of the patients sorted by the CONUT score.
Characteristics | All (N = 309) | CONUT < 2.5 (N = 214) | CONUT > 2.5 (N = 95) | P value |
Age, years | 63.4 ± 0.6 | 62.2 ± 0.7 | 66.2 ± 1.2 | 0.003 |
Gender | - | - | - | 0.416 |
Male | 228 (73.8) | 155 (72.4) | 73 (76.8) | - |
Female | 81(26.2) | 59(27.6) | 22(23.2) | - |
BMI, kg/m2 | 22.8 ± 0.2 | 23.1 ± 0.2 | 21.9 ± 0.3 | < 0.001 |
Comorbidities | - | - | - | - |
Diabetes mellitus | 38 (12.3) | 19 (8.9) | 19 (20.0) | 0.006 |
Hypertension | 117 (37.9) | 76 (35.5) | 41 (43.2) | 0.201 |
History of abdomen surgery | 70 (22.7) | 40 (18.7) | 30 (31.6) | 0.013 |
Preoperative laboratory measurements | - | - | - | - |
Hb, g/L | 123.9 ± 1.4 | 132.5 ± 1.3 | 104.5 ± 2.4 | < 0.001 |
Albumin, g/L | 39.0 ± 0.3 | 40.9 ± 0.3 | 34.6 ± 0.5 | < 0.001 |
CRP, mg/L | 5.2 ± 0.7 | 3.2 ± 0.6 | 9.6 ± 1.8 | < 0.001 |
WBC, x109/L | 5.87 ± 0.09 | 5.99 ± 0.10 | 5.61 ± 0.21 | 0.064 |
RBC, x1012/L | 4.14 ± 0.04 | 4.38 ± 0.04 | 3.60 ± 0.07 | < 0.001 |
Platelets, x109/L | 216.8 ± 3.8 | 221.4 ± 4.5 | 206.5 ± 7.4 | < 0.001 |
Total lymphocytes, x109/L | 1.56 ± 0.04 | 1.79 ± 0.04 | 1.04 ± 0.04 | < 0.001 |
Cholesterol, mmol/L | 4.60 ± 0.06 | 5.02 ± 0.07 | 3.64 ± 0.08 | < 0.001 |
Preoperative tumor biomarkers | - | - | - | - |
CA125, u/ml | 13.6 ± 0.8 | 11.8 ± 0.9 | 17.4 ± 1.7 | 0.001 |
CA199, u/ml | 27.9 ± 4.6 | 20.4 ± 2.8 | 43.9 ± 13.0 | 0.016 |
CEA, ng/ml | 5.8 ± 1.6 | 6.1 ± 2.3 | 5.1 ± 1.2 | 0.769 |
AFP, µg/L | 8.9 ± 5.8 | 11.7 ± 8.4 | 3.0 ± 0.5 | 0.487 |
Types of operative procedure | - | - | - | 0.498 |
Distal gastrectomy | 193(62.5) | 131(61.2) | 62(65.3) | - |
Total gastrectomy | 116(37.5) | 83(38.8) | 33(34.7) | - |
Intraoperative fluid utilization, ml | 2161 ± 35.7 | 2209 ± 41.1 | 2042 ± 69.4 | 0.034 |
Operative time, min | 271.8 ± 3.0 | 273.4 ± 3.6 | 268.4 ± 5.8 | 0.444 |
Estimated blood loss, ml | 106.1 ± 7.3 | 103.0 ± 9.3 | 112.9 ± 11.2 | 0.531 |
T factor | - | - | - | - |
T1 | 91(29.4) | 78(36.4) | 13(13.7) | < 0.001 |
T2 | 35(11.3) | 22(10.3) | 13(13.7) | 0.384 |
T3 | 42(13.6) | 23(10.7) | 19(20.0) | 0.029 |
T4 | 141(45.6) | 91(42.5) | 50(52.6) | 0.100 |
N factor | - | - | - | - |
N0 | 118(38.2) | 94(43.9) | 24(25.3) | 0.002 |
N1 | 44(14.2) | 30(14.0) | 14(14.7) | 0.868 |
N2 | 53(17.2) | 38(17.8) | 15(15.8) | 0.672 |
N3 | 94(30.4) | 52(24.3) | 42(44.2) | < 0.001 |
pTNM stage | - | - | - | - |
I | 102(33.0) | 80(37.4) | 22(23.2) | 0.014 |
II | 51(16.5) | 41(19.2) | 10(10.5) | 0.059 |
III | 148(47.9) | 88(41.1) | 60(63.2) | < 0.001 |
IV | 8(2.6) | 5(2.3) | 3(3.2) | 0.975 |
Postoperative stay, days | 13.6 ± 0.5 | 11.6 ± 0.5 | 14.1 ± 0.7 | 0.006 |
Postoperative complications | 91 (29.4) | 41 (19.2) | 50 (52.6) | < 0.001 |
Values in parentheses are percentages unless indicated otherwise; the other values are mean ± Sd. BMI, body mass index; Hb, Hemoglobin; CRP, C-reactive protein; WBC, White blood cells; RBC, Red blood cells. |
Postoperative complications in GC patients with low and high CONUT scores
The rate of postoperative complications in patients with a CONUT score < 2.5 was significantly lower than in patients with a CONUT score > 2.5 (19.2% vs 52.6%, P < 0.001) (Table 3). The rate of mild complications, including sustained fever with a temperature over 38.5 °C, incision infection, persistent utilization of total parenteral nutrition exceeding 2 weeks, postoperative blood transfusion, gastroplegia, abdominal or pelvic effusion, early postoperative bowel obstruction, and urinary tract infection, was significantly higher in the high CONUT score group (8.4% vs 34.7%, P < 0.001). A total of 40 patients suffered major complications, including postoperative active haemorrhage, intra-abdominal abscess, anastomotic leakage, duodenal stump fistula, septic shock, and single organ dysfunction, though there was not a significant difference between the two groups (11.2% vs 16.8%, P = 0.174) (Table 3). Only 1 patient died from severe cachexia and multiple organ dysfunction syndrome (MODS) after surgery. With regard to SSIs, there were 5 (1.6%) cases of surface incisional infection and 17 (5.5%) cases of deep space infection, with no significant difference between the two groups (0.9% vs 3.2%, P = 0.347; 5.1% vs 6.3%, P = 0.676).
Table 3
Comparison of postoperative complications in gastric cancer undergoing laparoscopic surgery with low and high CONUT score.
Postoperative complications | All (N = 309) | CONUT < 2.5 (N = 214) | CONUT > 2.5 (N = 95) | P value |
Overall complications | 91(29.4) | 41(19.2) | 50(52.6) | < 0.001 |
Mild complications (Grade I to II) | 42(13.6) | 17(7.9) | 25(26.3) | < 0.001 |
Fever > 38.5℃ after surgery | 9(2.9) | 4(1.9) | 5(5.3) | 0.204 |
Incision infection | 5(1.6) | 2(0.9) | 3(3.2) | 0.347 |
TPN > 2 weeks | 10(3.2) | 4(1.9) | 6(6.3) | 0.091 |
Postoperative blood transfusion > 2U | 5(1.6) | 2(0.9) | 3(3.2) | 0.347 |
Gastroplegia | 2(0.6) | 1(0.5) | 1(1.1) | 0.521 |
Early postoperative bowel obstruction | 10(3.2) | 4(1.9) | 6(6.3) | 0.091 |
Urinary tract infection | 1(0.3) | 0(0.0) | 1(1.1) | 0.307 |
Major complications (Grade III to IV) | 70(22.7) | 40(18.7) | 30(31.6) | 0.013 |
Postoperative active hemorrhage | 16(5.2) | 10(4.7) | 6(6.3) | 0.548 |
Abdominal/Pelvic effusion | 7(2.3) | 3(1.4) | 4(4.2) | 0.264 |
Intra-abdominal abscess | 17(5.5) | 11(5.1) | 6(6.3) | 0.676 |
Anastomotic leakage | 9(2.9) | 5(2.3) | 4(4.2) | 0.591 |
Anastomotic stenosis | 4(1.3) | 3(1.4) | 1(1.1) | 0.802 |
Duodenal stump fistula | 9(2.9) | 6(2.8) | 3(3.2) | 0.864 |
Septic shock | 3(1.0) | 0(0.0) | 3(3.2) | 0.028 |
Single organ dysfunction | 4(1.3) | 2(0.9) | 2(2.1) | 0.768 |
MODS | 1(0.3) | 0(0.0) | 1(1.1) | 0.307 |
Dead cases (Grade V) | 1(0.3) | 0(0.0) | 1(1.1) | 0.307 |
Surgical site infection, SSI | 25(8.1) | 13(6.1) | 12(12.6) | 0.051 |
Surface incisional infection | 5(1.6) | 2(0.9) | 3(3.2) | 0.347 |
Deep space infection | 20(6.5) | 11(5.1) | 9(9.5) | 0.153 |
Respiratory complications | 20(6.5) | 8(3.7) | 12(12.6) | 0.003 |
Cardiovascular complications | 7(2.3) | 3(1.4) | 4(4.2) | 0.264 |
Postoperative stay, days | 13.6 ± 0.5 | 11.6 ± 0.5 | 14.1 ± 0.7 | 0.006 |
Values in parentheses are percentages unless indicated otherwise; the other values are mean ± Sd; TPN, total parenteral nutrition; ICU, Intensive Care Unit; MODS, multiple organ dysfunction syndrome; SSI, Surgical Site Infection; Postoperative complications were classified from Grade I to V based on the Clavien-Dindo classification system, with Grade I to II defined as mild complications, Grade III to IV defined as major complications. |
Univariate and multivariate analysis of risk factors of short-term outcomes in GC
In the univariate analysis, age, Hb, CRP, RBCs, CONUT scores, type of operative procedure, pathological TNM classification of T1, T4, N0, and N3, and pathological stage of I and III were found to be risk factors with p value less than 0.05. Furthermore, age (P = 0.037; odds ratio (OR) = 2.237; 95% confidence interval (CI): 1.048–4.774), RBCs (P = 0.003; OR = 0.356; 95% CI: 0.180–0.707), and CONUT scores (P = 0.012; OR = 2.433; 95% CI: 1.218–4.862) were identified as independent risk indicators for postoperative complications in gastric cancer after laparoscopic gastrectomy (Table 4).
Table 4
Univariate and multivariate analysis of risk factors associated with postoperative complications in patients with gastric cancer undergoing laparoscopic surgery.
Characteristics | Postoperative complications (N = 91) | No postoperative complications (N = 218) | P value | Multivariate |
OR | 95%CI | P value |
Age, year | 68.2 ± 1.1 | 61.4 ± 0.7 | < 0.001 | 2.237 | 1.048–4.774 | 0.037 |
Gender | | | | | | |
Male | 70 (76.9) | 158 (72.5) | 0.418 | | | |
Female | 21(23.1) | 60(27.5) | 0.418 | | | |
BMI, kg/m2 | 22.2 ± 0.3 | 23.0 ± 0.2 | 0.059 | | | |
Comorbidities | | | | | | |
Diabetes mellitus | 14 (15.4) | 24 (11.0) | 0.286 | | | |
Hypertension | 39 (42.9) | 78 (35.8) | 0.242 | | | |
History of abdomen surgery | 20 (22.0) | 50 (22.9) | 0.855 | | | |
Preoperative laboratory measurements | | | | | | |
Hb, g/L | 113.6 ± 2.9 | 128.2 ± 1.4 | < 0.001 | 0.521 | 0.219–1.237 | 0.139 |
CRP, mg/L | 9.0 ± 1.8 | 3.5 ± 0.6 | < 0.001 | 1.193 | 0.500-2.849 | 0.691 |
WBC, x109/L | 5.85 ± 0.19 | 5.88 ± 0.11 | 0.881 | | | |
RBC, x1012/L | 3.78 ± 0.08 | 4.29 ± 0.04 | < 0.001 | 0.356 | 0.180–0.707 | 0.003 |
Platelets, x109/L | 216.0 ± 7.5 | 217.2 ± 4.5 | 0.887 | | | |
CONUT score | 3.7 ± 0.3 | 1.6 ± 0.1 | < 0.001 | 2.433 | 1.218–4.862 | 0.012 |
Albumin, g/L | 36.4 ± 0.6 | 40.1 ± 0.3 | < 0.001 | | | |
Total lymphocytes, x109/L | 1.33 ± 0.06 | 1.66 ± 0.05 | < 0.001 | | | |
Cholesterol, mmol/L | 4.20 ± 0.13 | 4.77 ± 0.07 | < 0.001 | | | |
Preoperative tumor biomarkers | | | | | | |
CA125, u/ml | 15.5 ± 1.4 | 12.8 ± 1.0 | 0.129 | | | |
CA199, u/ml | 38.7 ± 13.5 | 23.3 ± 3.2 | 0.126 | | | |
CEA, ng/ml | 6.2 ± 1.5 | 5.6 ± 2.2 | 0.869 | | | |
AFP, µg/L | 22.5 ± 19.4 | 3.3 ± 0.3 | 0.128 | | | |
Types of operative procedure | | | | 1.345 | 0.740–2.444 | 0.331 |
Distal gastrectomy | 49(53.8) | 144(66.1) | 0.043 | | | |
Total gastrectomy | 42(46.2) | 74(33.9) | 0.043 | | | |
Intraoperative fluid utilization, ml | 2082 ± 66.6 | 2195 ± 42.1 | 0.148 | | | |
Operative time, min | 272.7 ± 5.3 | 271.5 ± 3.7 | 0.853 | | | |
Estimated blood loss, ml | 124.2 ± 11.8 | 98.5 ± 9.1 | 0.110 | | | |
T factor | | | | | | |
T1 | 14 (15.4) | 77 (35.3) | < 0.001 | 1.131 | 0.353–3.622 | 0.836 |
T2 | 8 (8.8) | 27 (12.4) | 0.364 | | | |
T3 | 16 (17.6) | 26 (11.9) | 0.186 | | | |
T4 | 53 (58.2) | 88 (40.4) | 0.004 | 1.402 | 0.643–3.058 | 0.396 |
N factor | | | | | | |
N0 | 25(27.5) | 93(42.7) | 0.012 | 2.596 | 0.810–8.317 | 0.108 |
N1 | 14(15.4) | 30(13.8) | 0.710 | | | |
N2 | 10(11.0) | 43(19.7) | 0.063 | | | |
N3 | 42(46.2) | 52(23.9) | < 0.001 | 1.903 | 0.936–3.868 | 0.075 |
pTNM stage | | | | | | |
I | 19(20.9) | 83(38.1) | 0.003 | 1.141 | 0.302–4.311 | 0.846 |
II | 10(11.0) | 41(18.8) | 0.092 | | | |
III | 60(65.9) | 88(40.4) | < 0.001 | 2.897 | 0.986–8.511 | 0.053 |
IV | 2(2.2) | 6(2.8) | 0.780 | | | |
Postoperative stay, days | 20.7 ± 1.4 | 10.2 ± 0.2 | < 0.001 | | | |
Values in parentheses are percentages unless indicated otherwise; the other values are mean ± Sd. BMI, body mass index; Hb, Hemoglobin; CRP, C-reactive protein; WBC, White blood cells; RBC, Red blood cells; CONUT, Controlling Nutritional Status. |