Morphological Changes in the Colon Wall and Alterations in Endogenous Intoxication Markers in Patients with Obstructive Left-Sided Colon Cancer

The study examined morphological changes in the proximal and distal colon segments in patients with obstructive left-sided colon cancer (OLCC) and conducted a comprehensive assessment of endogenous intoxication markers and morphological alterations in the colon wall at various stages of OLCC progression. The progression of OLCC significantly increased serum endogenous intoxication levels, accompanied by disturbances in the antioxidant system and marked morphological alterations in the colon wall. These changes serve as predictors of purulent inflammatory processes and primary anastomosis leak. Dynamic quantitative assessment of serum procalcitonin (PCT) and C-reactive protein (CRP) levels in the early postoperative period proves to be an effective tool for predicting early postoperative complications, underscoring the clinical significance of these biomarkers. Objective: to assess the relationship between endogenous intoxication markers, acute phase proteins, and morphological changes in the colon wall in patients with OLCC. Material and Methods. The study examined serum levels of endogenous intoxication markers in 115 patients with OLCC during disease progression and 20 apparently healthy individuals. The levels of middle molecules and lipid peroxidation markers (malondialdehyde (MDA) and diene conjugates (DC)) were analyzed in the patient serum and the colon wall. Additionally, the activity of antioxidant system enzymes, including catalase (CAT), superoxide dismutase (SOD), and ceruloplasmin (CP), was studied. The levels of acute phase proteins, specifically CRP and PCT, were also evaluated. Tissue samples up to 0.5 cm in size were obtained from the edges of the proximal and distal colon segments after colectomy for histological examination. These samples were fixed in a 10% formalin solution and processed through alcohol solutions. Paraffin sections, 5-10 µm thick, were prepared and stained with hematoxylin and eosin to evaluate the morphological changes under light microscopy at magnifications of ×100, ×200, and ×400. Results. As OLCC progressed, serum markers of endogenous intoxication increased while antioxidant system effectiveness declined. At various stages of disease progression, the leukocytic index of intoxication, intoxication index, and middle molecule levels were 4.37 (3.45; 5.67) a.u., 8.71 (7.89; 9.21) a.u., and 0.56 (0.43; 1.26) a.u., respectively (p<0.05). In healthy individuals, these values were 0.70 (0.45; 1.1) a.u., 0.95 (0.67; 1.54) a.u., and 0.27 (0.12; 0.67) a.u., respectively. Middle molecule levels progressively increased during OLCC progression: 0.42 (0.38; 0.43) a.u. at the compensation stage, 0.56 (0.51; 0.58) a.u. at the sub-compensation stage, and 0.72 (0.69; 0.73) a.u. at the decompensation stage (p1<0.01, p2<0.01, p3<0.01) compared to a normal level of 0.23 (0.18; 0.25) a.u. Furthermore, as the disease progressed, a gradual rise in lipid peroxidation products, specifically MDA, was observed in both serum and the colon wall. At the compensation, sub-compensation, and decompensation stages, serum MDA levels were 6.39 (6.25; 6.42) nmol/mL, 7.88 (7.62; 7.92) nmol/mL, and 8.11 (8.05; 8.15) nmol/mL, respectively (p1<0.001, p2<0.01, p3<0.05), compared to a normal level of 3.14 (2.58; 3.17) nmol/mL. Similarly, MDA levels in the colon wall increased progressively across the stages, reaching 6.82 (6.49; 6.62) nmol/mL, 7.92 (7.81; 7.89) nmol/mL, and 8.29 (8.11; 8.15) nmol/mL (p1<0.001, p2<0.01, p3<0.05). Serum DC levels increased from 3.11 (3.02; 3.18) a.u. to 4.69 (4.53; 4.82) a.u. during OLCC progression (p1<0.01, p2<0.01, p3<0.01) compared to a normal level of 1.41 (1.32; 1.46) a.u. Similarly, DC levels in the colon wall rose to 4.72 (4.63; 4.80) a.u. compared to a normal level of 1.41 (1.32; 1.46) a.u. (p1<0.01, p2<0.01, p3<0.01). Morphological changes in the colon wall tissues caused by the progressive obstruction process were also studied by assessing the intensity of protein peroxidation processes (POM 356, POM 370, POM 430, POM 530). As the disease progressed, the levels of these peroxidation products significantly increased compared to the control group (p1<0.001, p2<0.01, p3<0.01). At the same time, the antioxidant system exhibited a decrease in CAT and SOD levels. At different stages of OLCC, CAT serum levels were as follows: 8.08 (7.65; 9.12) H2O2/mL at the compensation stage, 6.32 (5.75; 7.31) H2O2/mL at the sub-compensation stage, and 5.27 (4.59; 5.75) H2O2/mL at the decompensation stage compared to a normal value of 12.36 (12.11; 12.65) H2O2/mL (p1<0.001, p2<0.01, p3<0.01). Serum SOD levels also decreased with disease progression: 42.43 (31.75; 51.84) a.u. at the compensation stage, 35.65 (24.72; 45.53) a.u. at the sub-compensation stage, and 32.18 (18.72; 41.15) a.u. at the decompensation stage (p1<0.001, p2<0.01, p3<0.01). The changes in serum CP levels also exhibited a reverse trend. At the compensation stage, the level was higher than the normal value (39.21 a.u.), indicating the body compensatory response to the increased lipid peroxidation products. However, with further progression of OLCC, the CP level decreased to 16.12 (15.26; 16.87) a.u. at the decompensation stage (p1<0.001, p2<0.01, p3<0.01). The changes in serum CRP levels indicated inflammatory response development: on days 2-3 of the postoperative period, the CRP level increased to 15.2 (14.8; 16.8) mg/L, and by day 6, it reached 30.1 (27.8; 34.7) mg/L. Serum PCT concentration also increased: on day 2, it was 1.27 (0.87; 1.45) ng/mL; on day 3 - 2.87 (2.34; 3.24) ng/mL; and on day 6 - 3.21 (2.87; 3.65) ng/mL. These changes are indicative of systemic inflammatory response syndrome, necessitating the administration of antibiotic therapy and, if necessary, further surgical interventions. After resection, morphological examination of tissue samples from the proximal and distal colon segments revealed significant changes associated with impaired tissue tropism. These included disruptions in intramural hemodynamics, particularly arteriolar and venular paralysis, which indicated the presence of vascular stasis and tissue damage. Furthermore, inflammatory changes were observed in the intestinal wall, marked by leukocyte infiltration across the different wall layers. The severity of this infiltration varied according to the stage of disease progression. Conclusions. The stage of intestinal endogenous intoxication directly affects the morphological changes in the intestinal wall. These changes are closely linked to the stage of tumor progression in the colon. Studying the morphological changes at different stages of colon cancer enables more precise prognostication of disease progression and helps define potential surgical strategies.