FEATURES OF LABORATORY MONITORING FOR EARLY DETECTION OF COLONIC ANASTOMOSIS LEAK

Aims. The work was aimed at identifying the characteristics of the dynamics of changes in laboratory parameters in patients with colonic anastomosis leak for early diagnosis of postoperative complications. Materials and methods. The dynamics of laboratory parameters of blood and peritoneal effusion on the first to seventh postoperative day was studied in 102 patients operated on for colorectal cancer. All patients had complete resection of the colon with tumour; surgery was ended with interintestinal anastomosis. A single-layer continuous blanket anastomosis and machine stapling anastomosis were used. The following laboratory parameters were investigated: C-reactive protein, pyruvate and lactate concentration, pH of peritoneal effusion and leukocytic index of intoxication. Results. The development of leaking intestinal anastomosis was detected in 8.8%. The most clinically significant indicators for early diagnosis of anastomosis leak were leukocytic index of intoxication, C-reactive protein, pH of effusion in the abdominal cavity and the ratio of the effusion lactate to blood plasma lactate. Conclusions. The combined use of these parameters allows suspecting with a high degree of reliability of the leak of intestinal anastomosis as early as on the third day after surgery.

Many authors highlight that the development of IAD is associated with the worsening of oncological results and 5-year overall survival in patients with colon cancer. In particular, IAD decreases overall survival and increases the rate of tumor recurrence regardless of the stage of the malignant process [10]. According to the published data, the rate of local tumor recurrence varies from 0.5 to 30% depending on the methods of diagnostics and the degree of IAD severity [11]. The research group that studied rectal cancer defined three levels of IAD severity: level A -IAD that does not require active therapeutic measures, level B -IAD that requires active therapeutic measures without relaparotomy, and level C -IAD that requires relaparotomy [12].
Clinical and oncological results of the treatment of colorectal cancer in patients with IAD directly depend on the stage of diagnostics of this complication. Early diagnostics of IAD plays a crucial role in the prevention of severe septic complications. The anastomotic dehiscence is rarely diagnosed before the 5 th day after the surgery, usually, it is revealed on the 4 th -8 th day after the surgery [3; 9; 13]. It is explained by the fact that the clinical picture is not always manifested as peritonitis or intraabdominal and can look like fever, intestinal obstruction or even diarrhea.
The diagnostics of anastomotic dehiscence at the early stages allows avoiding numerous complications and decreasing the lethality rate [2]. In clinical practice, the gold standard of anastomotic dehiscence diagnostics is computed tomography, especially, with intravenous and intraintestinal contrasting [3; 9].
Presently, there are no known specific markers of anastomotic dehiscence in colorectal surgery. One of the early markers of anastomotic dehiscence is C-reactive protein (CRP). Its level increases by the 3 rd -4 th day after the surgery, which is associated with the systemic inflammatory reaction that develops as a result of intraabdominal septic complications. Still, the sensitivity and specificity of the test remain doubtful and the reference values range from 150 to 250 mg/L [13][14][15].
Several studies demonstrated that a prognostic significant level of CRP is 180 mg/L and higher. This provides grounds for a high prognostic significance of CRP in patients with anastomosis [16]. At the same time, the results of some meta-analyses showed that the concentration of CRP on the 3 rd -5 th day after the surgery is a useful negative prognostic test and not a good positive predictor [1; 17]. Probably, this is associated with the fact that the concentration of CRP in blood samples can be a precise prognostic factor of the lethal outcome caused by any reason [18].
Another direction in the search for IAD predictors is the study of peritoneal exudate for the cytokines IL-6, IL-10, and TNF-α. Several studies showed the increase in the levels of these inflammatory mediators within the 1 st three days after the surgery in patients with IAD [19]. Apart from cytokines, peritoneal exudate was used for the study of the concentration of biochemical markers that indicate tissue hypoxia, like pyruvate and lactate [20; 21]. It was proposed to use the pH level of peritoneal exudate as a criterion of the evaluation of tissue ischemia and the development of inflammatory complications. Several studies demonstrated that a decrease in the pH level to 6.8 on the 3 rd day after the surgery could indicate the development of intraabdominal complications, including IAD. The pH level of the exudate as a predictor of IAD is highly sensitive (98.7%) and specific (94.7%) [22].
In the present study, the authors analyzed the daily dynamics of the changes in laboratory blood parameters and peritoneal exudate in the post-operative period in patients that underwent radical surgery for malignant neoplasms in the colon with the primary reconstruction of the colon continuity. The study protocol followed guidelines for experimental investigation with human subjects in accordance with the Declaration of Helsinki and was approved by the ethics committee. Written informed consent was obtained from each patient (or official representative) before the study. Intestinal anastomotic dehiscence was registered in 9 patients (8.1%) that formed the group of patients with IAD. The rate of the development of IAD did not depend on the localization of the tumor: in 6 patientsafter the resection of the sigmoid colon (7.6%) and in 3 patientsafter the left-sided hemicolectomy (12.5%) (χ 2 -0.49, p>0.05). Male patients prevailed in this group (6 patients, 67%). In the majority of cases, the tumor process of stage III was diagnosed (7 patients, 78%). The analysis of the hematological parameters revealed clinically significant results in the dynamics of the levels of leukocytosis, ESR, and the leukocytal intoxication index (LII). It should be mentioned that significant differences in the levels of CRP between the groups of patients with IAD and without complications start to be registered from Day 2 after the surgery, while the levels of lactate in blood plasma start to differ from Day 5 after the surgery (Figure 2).   The analysis of the daily dynamics of the specified coefficients and the comparison of their levels between the groups indicate the appearance of significant differences on Day 2 after the surgery. On Day 3, these differences become highly significant ( Figure 4). Thus, the level of kCRP in patients with IAD exceeds the control parameter on Day 2 by 21% (p=0.016), and from Day 3, this difference starts to exceed it by 100% (p<0.001). The difference in kLac levels indicates highly significant differences from Day 2 of the observation when the difference with the control reaches 69% (p=0.002). On Day 3, this parameter exceeds the control by 3 times (p<0.001) and the tendency toward the increase remains.