CAR as a Predictor of Specific Postoperative Complications

For this analysis, the patients were stratified according to the CAR cutoff: high CAR (≥2.6) versus low CAR (<2.6). Complications occurred in 39 (92.9%) of the 42 patients with CAR≥2.6 and in 41 (36.6%) of the 112 patients with CAR<2.6 (Table 5). The difference between groups was statistically significant (P<0.001).

The incidence of specific complications was examined in each group. Compared to patients with high CAR, those with low CAR on POD3 had a lower incidence of mild complications (grade I or II; 50.0% vs 26.8%, P<0.001), as well as a lower incidence of severe complications (grade III or higher; 42.9% vs 9.8%, P<0.001) (Table 5). In particular, infectious complications occur significantly more frequently in patients with high CAR on POD3 (54.8% vs 16.1%, P<0.001) (Table 5).


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Table 5

Usefulness of CAR as a Predictor of Surgical Site Infection, Infective Complications, and Anastomotic Leakage

For predicting surgical site infection (Figure 2), POD3 CAR exhibited an AUC of 0.760 (95% CI=0.685–0.825), the sensitivity of 75.00%, and specificity of 68.85%. For predicting infectious complications (Figure 3), POD3 CAR exhibited an AUC of 0.702 (95% CI=0.623–0.773), the sensitivity of 59.09%, and specificity of 74.55%. For predicting anastomotic leakage (Figure 4), POD3 CAR exhibited an AUC of 0.798 (95% CI=0.726–0.859), the sensitivity of 100%, and specificity of 58.11%.

DISCUSSION

In this single-center retrospective analysis of 154 patients who underwent radical surgery for colorectal carcinoma, we found evidence suggesting that high levels of preoperative mGPS (P=0.002), preoperative CAR (P=0.019), POD3 CAR (P<0.001) and POD3 poGPS (P<0.001) can significantly affect postoperative complications after surgery for colorectal cancer. On receiver operating characteristic curve analysis, we found good predictive value for all three inflammation-based scores evaluated. However, CAR on POD3 provided the highest PPV, which is of particular importance in the clinical setting.

Surgery induces local tissue damage, physical barrier damage, and potential exposure to environmental and commensal microorganisms, all of which can lead to localized inflammation. Moreover, patients with surgery often undergo other invasive procedures such as venous catheterization, general anesthesia, endotracheal intubation, and catheterization. These procedures damaged the skin and epithelial defenses, causing inflammation at distant anatomical sites. Therefore, monitoring inflammation perioperatively is essential, as well as to understand the relationship between inflammation and the risk of postoperative complications. Indeed, an increasing number of studies are being designed to examine the role of the systemic inflammatory response as a contributing factor to postoperative complications.

Both preoperative and postoperative CRP levels have been reported as important predictors of postoperative survival in patients with colorectal cancer.9,15,16 CRP is an important marker of inflammation, and its elevation in cancer patients is mainly due to the inflammatory response to the tumor and surgery. Nason et al17 reported that CRP on POD3 is a useful predictor of infectious complications in patients who undergo colorectal surgery. However, in the clinical setting, there are several limitations to the use of postoperative CRP as a predictor of postoperative complications. The main disadvantages are low predictive accuracy and high time lag.18,19 CRP and white blood cell levels increase non-specifically in response to surgical stress.20 Moreover, as suggested by a recent study, postoperative changes in CRP levels are noted later than the changes in other inflammatory markers such as interleukin-6.19 Therefore, CRP alone is not a sufficiently sensitive descriptor of the inflammatory state of patients in the early stages after surgery.

In order to improve the accuracy of the prediction of postoperative complications, CAR considers CRP levels concomitantly with albumin levels. Hepatocytes synthesize albumin. And albumin serves as a multifunctional protein with antioxidant, immunomodulatory, and detoxifying action.21 Among patients with malignant tumors, albumin levels differ significantly between survivors and non-survivors.22 Some scholars have pointed out that decreased albumin levels reflect negative nitrogen balance and a decreased rate of toxic metabolite clearance. Abundant expression of inflammatory factors in the plasma causes damage to the endothelial cells of capillaries, which allows albumin to leak through the damaged capillary endothelium into the interstitial space, resulting in hypoproteinemia,21,23 which is an important prognostic index of surgical outcomes.24 In our study, the combined indices of CRP and albumin (CAR, mGPS, poGPS) provided superior prognostic efficacy compared to that noted for CRP. CAR on POD3 exhibited the highest probability to detect patients at risk (PPV=83.2%), and the overall predictive value of preoperative CAR was poor. Preoperative mGPS (PPV=100.0%) and poGPS on POD3 (PPV=100.0%) exhibited a higher probability to adequately identify patients with high risk when the cutoff value was 2.

Alazawi et al reported that most patients who underwent surgery had a systemic inflammatory response on POD3,25 which is consistent with our present findings. Specifically, we found high predictive value for all inflammation-based prognosis scores obtained on POD3, and the incidence of postoperative complications was significantly higher in patients with CAR≥2.6 than in those with CAR<2.6 on POD3 (overall incidence, as well as the incidence of severe complications and that of infectious complications).

In our study, subgroup analysis confirmed the good prognostic value of CAR on POD3 for predicting the 30-day incidence of surgical site infection (AUC=0.760; 95% CI=0.685–0.835; P=0.016), infectious complications (AUC=0.702; 95% CI=0.623–0.773), and anastomotic leakage (AUC=0.798; 95% CI=0.726–0.859). Surgical site infection is the most common complication after surgery, with a high incidence and strong impact on the duration of hospitalization.26 In a prospective study by Goulart et al.27 CAR was superior to white blood cell count and procalcitonin as an independent predictor of surgical site infection. On the other hand, CRP was reported as the best postoperative inflammatory response marker for predicting anastomotic leakage, providing high sensitivity.28 Our present findings confirm the usefulness of CRP as an inflammatory marker but highlight the benefit of considering albumin concomitantly with CRP (especially as CAR) to improve the accuracy of predicting the risk of complications after radical surgery for colorectal carcinoma.

In recent years, the concept of enhanced recovery after surgery has become increasingly adopted in the field of colorectal surgery. Within this framework, minimally invasive surgery is preferred, as it helps reduce surgical trauma and ensuing inflammatory response to surgical stress as much as possible. However, various complications may still occur. Therefore, further studies are warranted to elucidate the extent to which such principles can minimize inflammatory response to surgical stress.

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