Abstract
Purpose
Early detection is the most critical factor in effectively managing complications following routine colorectal surgery. This study aimed to identify the most effective and useful factors related to body composition and inflammation in the selection of high-risk groups for postoperative complications.
Methods
A retrospective review of 109 patients who underwent elective surgery between January 2021 and May 2023 was conducted. Patients were categorized according to the Clavien-Dindo classification into those discharged without complications (grade 0), those with minor complications (grades 1 and 2), and those with major complications (grade 3+). The characteristics of patients without complications and those with minor or major complications were compared.
Results
Twenty patients developed only minor complications. Bowel obstruction at diagnosis and elevated C-reactive protein (CRP) levels at 2 days postoperatively were statistically significant factors. Eleven patients experienced major complications, and a low lymphocyte count at 2 days postoperatively was a significant predictor of complications. Receiver operating characteristic analysis revealed that CRP levels >125.6 mg/L on postoperative day 2 and lymphocyte count <905 cells/µL were associated with a higher likelihood of minor and major complications.
Conclusion
These findings suggest that monitoring inflammatory markers on postoperative day 2 may help identify patients at risk of complications, enabling early intervention. Further prospective studies are warranted to validate these predictive markers and improve surgical outcomes.
Keywords: Colorectal neoplasms, Postoperative complications, C-reactive protein, Lymphocyte count
INTRODUCTION
The Enhanced Recovery After Surgery (ERAS) protocol has recently become a standard approach for managing patients during the perioperative period of colorectal cancer (CRC) treatment. The systematic strategy is aimed at accelerating patient recovery by minimizing the use of potentially counterproductive medications or procedures [1–3]. However, in cases where patients develop complications following CRC surgery, the application of the ERAS protocol is restricted, necessitating the exploration of alternative therapeutic approaches. The complications have the potential to prolong the patient's recovery period, which can result in adverse outcomes, including morbidity and mortality.
Surgical complications that can occur after CRC surgery are broadly categorized as surgical site infections and gastrointestinal (GI) motility disorders [4–6]. Surgical site infections are further classified as superficial, deep, and organ/intra-abdominal infections. GI motility disorders primarily manifest as postoperative ileus syndrome, which occurs 2 to 5 days postoperatively. Complications have been documented in approximately one-third of all surgical patients, with superficial infections accounting for 13%, organ infections for 3% to 10%, and GI motility disorders for 5.3% to 24% of all infections [4].
Early detection of postoperative complications and timely administration of appropriate treatment are of the utmost importance to improve patient outcomes. Regarding wound infections, the timely implementation of drainage measures has been shown to reduce the necessity and duration of antibiotic treatment, as well as the overall length of hospital stay. In the event of anastomotic leakage, timely reoperation has been shown to reduce the likelihood of postoperative intensive care unit admission and use of inotropes. This can lead to a reduction in the severity of sepsis, associated additional healthcare costs, and length of hospital stay. Many studies have identified various risk factors that influence the development of complications after CRC surgery. Several factors have been identified that contribute to postoperative complications, including patient nutritional status, chronic inflammatory status, and immune function, as well as surgery-related factors such as emergency surgery, surgery time, blood loss, intra-abdominal cavity contamination, and blood transfusion [7]. In recent years, imaging methods for measuring the skeletal muscle mass and fat area have been widely adopted to evaluate the nutritional status of patients [8–10]. Furthermore, systemic inflammatory response indicators that combine neutrophils, lymphocytes, monocytes, and platelets have been developed to reflect the chronic inflammatory state of patients with cancer. The relationship between these indicators and prognosis has been studied [11–13].
However, existing studies have primarily focused on long-term survival, and there is a dearth of research on the risk factors for short-term postoperative complications. Therefore, this study assessed various indicators of nutritional and inflammatory status in patients with CRC with the aim to identify the most effective and useful factors in the selection of high-risk groups for postoperative complications.
METHODS
Ethics statement
This study was approved by the Institutional Review Board of Chosun University Hospital (No. 2023-08-021-003). The requirement for written informed consent was waived due to the use of deidentified data and the retrospective nature of the study.
Patients
This retrospective study included 109 patients who underwent elective CRC surgery between January 2021 and May 2023. Patients were subjected to follow-up evaluations at 3-month intervals for the initial 3 years following hospital discharge and subsequently transitioned to semiannual follow-ups for the subsequent 2 years.
Data collection
At the time of admission, patients were required to provide baseline clinical information, including but not limited to the following: patient demographics (age [≥65 years or <65 years], sex [male or female], height, weight, and comorbidities) and cancer details. The following data were obtained from pathology reports: tumor location (colon vs. rectum), tumor invasion (T category), lymph node metastasis (N category), lymphovascular invasion, and perineural invasion. Medical records were reviewed to determine the length of stay and presence and severity of complications. Patient staging was determined using computed tomography (CT) scans obtained at the time of diagnosis, and data regarding the presence of bowel obstruction were collected. A comprehensive review of the surgical and anesthesia notes was conducted to obtain pertinent information regarding the surgical approach (open vs. laparoscopic), duration of the procedure, and American Society of Anesthesiologists (ASA) physical status. Cancer staging was performed according to guidelines of the American Joint Committee on Cancer (AJCC), 8th edition [14].
Measurement of body composition
Skeletal muscle mass was measured using abdominopelvic CT images obtained at the time of preoperative CRC diagnosis, and the total psoas area index (TPAI) was used as the measurement index. The TPAI is a normalized value calculated by multiplying the length of the longest axis of the right and left psoas muscles on the axial CT L3 slice by the length of the perpendicular axis, and dividing by the square of the height [15]. The TPAI threshold for sarcopenia was established with distinct cutoffs for men and women, with values of <385 mm2/m2 for women and <545 mm2/m2 for men [10, 16]. Body mass index (BMI) was calculated based on the patient's height and weight measured during the patient's hospital stay. The reference range is between 18.5 and 23 kg/m2, with a BMI of <18.5 kg/m2 categorized as underweight, 23‒25 kg/m2 as overweight, and ≥25 kg/m2 as obese [17].
Quantitative analysis of the superficial and visceral fat areas was conducted for 87 of the 109 patients, with measurements expressed in Hounsfield units at the axial L3 level. The analysis was performed using CT images obtained at the time of diagnosis.
Measurement of systemic inflammation markers
Preoperative blood test results were based on peripheral blood samples collected within 30 days of surgery. Neutrophil, lymphocyte, and platelet counts, serum carcinoembryonic antigen levels, albumin concentration, and total protein were collected. After the surgical intervention, complete blood cell count, differential count, and C-reactive protein (CRP) levels were collected every morning from postoperative day (POD) 1 to 5.
Classification of postoperative complications
The postoperative complications experienced by the patients were collected according to the Clavien-Dindo classification of surgical complications [18]. The classification system was further subdivided into 6 grades: grade 0, absence of complications; grade I, wound-related complications and postoperative bowel obstruction; grade II, postoperative blood transfusion and antibiotic use; grade III, imaging procedures and reoperation due to bowel obstruction or anastomotic leak; grade IV, intensive care unit management; and grade V, death. The study findings were subsequently divided into 3 distinct groups: no complications at grade 0 (group A), minor complications at grades 1 and 2 (group B), and major complications at grades 3, 4, and 5 (group C).
Statistical analysis
First, the analysis was conducted by dividing the patients into those without complications (group A) and those with complications (groups B+C). Second, group B was compared with group A. Group C was compared with groups A+B to reach clinical significance. The normality of variables was assessed using the Kolmogorov-Smirnov test. Categorical data are presented as absolute frequencies and percentages, and numerical data are presented as means, standard deviations, and ranges with minimum and maximum values. Qualitative datasets were compared using the chi-square or Fisher exact test. For quantitative data, the Mann-Whitney U-test was used. With the statistically significant variables in the univariable test, a backward stepwise approach to multivariable analysis was performed using binary logistic regression to identify factors associated with a high rate of postoperative complications in colorectal cancer surgery. The degree of association was estimated using the corresponding odds ratio and 95% confidence interval, and statistical significance was set at a P-value of <0.05. Receiver operating characteristic (ROC) curve analysis was performed to determine the appropriate cutoff values for continuous variables that were significantly associated with either minor or major complications in the multivariate analysis. The discriminatory ability of the test was assessed by estimating the area under the curve (AUC). Statistical analyses were performed using IBM SPSS ver. 29 (IBM Corp).
RESULTS
Demographic characteristics
This study included 109 patients with a mean age of 69 years and a median follow-up period of 290 days; 70 patients (64.2%) were aged 65 years or older, and 70 patients (64.2%) were male (Table 1). Of the patients, 78 (71.6%) had been diagnosed with colon cancer and 31 (28.4%) had been diagnosed with rectal cancer. At the time of diagnosis, 17 patients (15.6%) exhibited signs of obstruction on CT imaging or physical examination, and 31 patients (28.4%) had ASA physical status of III or higher. A total of 91 patients (83.5%) underwent laparoscopic surgery, and the mean operative time for laparoscopic and open surgery was 201.0±54.5 minutes (range, 105‒435 minutes). Pathological examination revealed a high proportion of cases classified as stages II and III, with 8 cases (7.3%) classified as stage 0, 17 (15.6%) as stage I, 44 (40.4%) as stage II, 32 (29.4%) as stage III, and 8 (7.3%) as stage IV.
Table 1.
Clinicopathologic characteristics of the patients (n=109)
| Characteristic | Value |
|---|---|
| Age (yr) | |
| <65 | 39 (35.8) |
| ≥65 | 70 (64.2) |
| Sex | |
| Male | 70 (64.2) |
| Female | 39 (35.8) |
| Obstruction sign | |
| No | 92 (84.4) |
| Yes | 17 (15.6) |
| Tumor stage | |
| 0 | 8 (7.3) |
| I | 17 (15.6) |
| II | 44 (40.4) |
| III | 32 (29.4) |
| IV | 8 (7.3) |
| ASA physical status | |
| I | 17 (15.6) |
| II | 61 (56.0) |
| III | 30 (27.5) |
| IV | 1 (0.9) |
| Operation type | |
| Laparotomy | 18 (16.5) |
| Laparoscopy | 91 (83.5) |
| Tumor site | |
| Colon | 78 (71.6) |
| Rectum | 31 (28.4) |
| Duration of operation (min) | 201.0±54.5 (105–435) |
| Clavien-Dindo classification | |
| 0 | 78 (71.6) |
| I | 1 (0.9) |
| II | 19 (17.4) |
| III | 8 (7.3) |
| IV | 2 (1.8) |
| V | 1 (0.9) |
| Postoperative length of stay (day) | 12.77±10.9 (5–85) |
| Group A (no complications) (n=78) | 8.53±1.73 (5–15) |
| Group B (minor complications) (n=20) | 15.85±4.50 (11–29) |
| Group C (major complications) (n=11) | 37.27±20.32 (12–85) |
Values are presented as number (%) or mean±standard deviation (range).
ASA, American Society of Anesthesiologists.
Of 109 patients, 31 (28.4%) experienced postoperative complications. Of these, 20 (18.3%) were classified as having minor complications (group B), and 11 (10.1%) as having major complications (group C). Among the 20 patients having minor complications, 1 patient exhibited a Clavien-Dindo grade I complication and was discharged from the hospital without receiving antibiotics. The patient improved with wound drainage alone. The 19 patients classified as having grade II included 10 patients who received antibiotics for wound complications, 4 patients with suspected anastomotic leakage, 4 patients with postoperative ileus, and 2 patients who received transfusions; categories were not mutually exclusive, as 1 patient had both ileus and transfusion. Among the 11 patients with major complications, 1 patient was classified as having grade IIIa complications and received percutaneous drainage of intra-abdominal abscesses guided by ultrasound and antibiotics at the site of the anastomotic leak on POD 6. Seven patients underwent reoperation under general anesthesia for grade IIIb. Of these, 1 patient underwent adhesiolysis on POD 40 for recurrent postoperative bowel obstruction and 6 patients underwent reoperation due to anastomotic leakage at the surgical site (1 patient on POD 6; 2 patients on POD 7; 1 patient each on PODs 10 and 14; and 1 patients on POD 19). Two patients with grade IV underwent reoperation on PODs 2 and 4, and needed intensive care unit care after reoperation. One patient with grade V underwent a subsequent surgical procedure due to anastomotic leakage on POD 10 and died due to pulmonary complications on POD 58.
The 78 patients were discharged without any major complications (group A) and had an average hospital stay of 8.53 days (range, 5‒15 days). Patients with minor complications (group B) had an average hospital stay of 15.85 days (range, 11‒29 days). Patients with major complications (group C) spent an average of 37.27 days (range, 12‒85 days) in the hospital.
Risk factors for complications
Clinical and pathological nature
Statistically significant differences were identified between groups B+C and group A for the occurrence of complications, including the presence of obstruction symptoms at diagnosis, ASA physical status, operation types, and duration of surgery (Table 2).
Table 2.
Univariable analysis for group A versus groups B+C
| Variable | Total (n=109) | Group A (n=78) | Groups B+C (n=31) | P-value |
|---|---|---|---|---|
| Clinicopathologic factor | ||||
| Age (yr) | 0.687 | |||
| <65 | 39 (35.8) | 27 (34.6) | 12 (38.7) | |
| ≥65 | 70 (64.2) | 51 (65.4) | 19 (61.3) | |
| Sex | 0.354 | |||
| Male | 70 (64.2) | 48 (61.5) | 22 (71.0) | |
| Female | 39 (35.8) | 30 (38.5) | 9 (29.0) | |
| Obstruction sign | 0.003* | |||
| No | 92 (84.4) | 71 (91.0) | 21 (67.7) | |
| Yes | 17 (15.6) | 7 (9.0) | 10 (32.3) | |
| Tumor stage | 0.783 | |||
| 0–II | 69 (63.3) | 50 (64.1) | 19 (61.3) | |
| III–IV | 40 (36.7) | 28 (35.9) | 12 (38.7) | |
| ASA physical status | 0.015* | |||
| I–II | 78 (71.6) | 61 (78.2) | 17 (54.8) | |
| III–IV | 31 (28.4) | 17 (21.8) | 14 (45.2) | |
| Operation type | 0.026* | |||
| Laparotomy | 18 (16.5) | 9 (11.5) | 9 (29.0) | |
| Laparoscopy | 91 (83.5) | 69 (88.5) | 22 (71.0) | |
| Tumor site | 0.578 | |||
| Colon | 78 (71.6) | 57 (73.1) | 21 (67.7) | |
| Rectum | 31 (28.4) | 21 (26.9) | 10 (32.3) | |
| Duration of operation (min) | 201.0±54.5 | 191.5±43.7 | 225.1±70.4 | 0.030* |
| Body composition | ||||
| TPAI | 0.741 | |||
| Normal | 93 (85.3) | 66 (84.6) | 27 (87.1) | |
| Sarcopenia | 16 (14.7) | 12 (15.4) | 4 (12.9) | |
| Body mass index (kg/m2) | 0.747 | |||
| <18.5 (Underweight) | 15 (13.8) | 12 (15.4) | 3 (9.7) | |
| 18.5–23 (Normal) | 33 (30.3) | 23 (29.5) | 10 (32.3) | |
| 23–25 (Overweight) | 16 (14.7) | 10 (12.8) | 6 (19.4) | |
| >25 (Obese) | 45 (41.3) | 33 (42.3) | 12 (38.7) | |
| Superficial fat area (HU) (n=87)a | 124.72±64.66 | 119.82±58.60 | 136.00±77.20 | 0.314 |
| Visceral fat area (HU) (n=87)a | 135.17±72.76 | 137.29±70.70 | 130.00±78.70 | 0.763 |
| Preoperative albumin (g/dL) (n=105)b | 3.89±0.51 | 3.93±0.50 | 3.82±0.50 | 0.223 |
| POD 1 albumin (g/dL) (n=103)c | 3.16±0.36 | 3.18±0.30 | 3.10±0.30 | 0.433 |
| Preoperative total protein (g/dL) (n=92)d | 6.88±0.63 | 6.90±0.60 | 6.83±0.60 | 0.476 |
| Systemic inflammatory response index | ||||
| POD 2 neutrophil count (cells/μL) (n=104)e | 7,644.03±302.60 | 7,215.41±319.02 | 8,701.30±639.15 | 0.030* |
| POD 2 lymphocyte count (cells/μL) (n=104)e | 1,181.44±47.73 | 1,283.92±52.71 | 928.70±81.40 | 0.001* |
| POD 2 CRP level (mg/L) (n=102)f | 129.11±6.31 | 112.34±5.93 | 170.60±7.16 | <0.001* |
| Preoperative lymphocyte count | 0.083 | |||
| Normal (>1,500 cells/μL) | 70 (64.2) | 54 (69.2) | 16 (51.6) | |
| Lymphopenia | 39 (35.8) | 24 (30.8) | 15 (48.4) |
Values are presented as number (%) or mean±standard deviation. Group A, patients with no complications; group B, patients with minor complications; and group C, patients with major complications. Group sizes differ across categories because of missing data.
ASA, American Society of Anesthesiologists; TPAI, total psoas area index; HU, Hounsfield unit; POD, postoperative day; CRP, C-reactive protein.
Group A, n=61; groups B+C, n=26.
Group A, n=76; groups B+C, n=29.
Group A, n=73; groups B+C, n=30.
Group A, n=69; groups B+C, n=23.
Group A, n=74; groups B+C, n=30.
Group A, n=72; groups B+C, n=30.
P<0.05.
A comparison of the group A and B demonstrated a statistically significant difference in the prevalence of obstruction at diagnosis (P=0.003) and between patients with ASA physical status I–II and III–IV (P=0.036). However, no significant variation was observed with respect to other factors (Table 3).
Table 3.
Univariable analysis for group A versus group B
| Variable | Total (n=98) | Group A (n=78) | Group B (n=20) | P-value |
|---|---|---|---|---|
| Clinicopathologic factor | ||||
| Age (yr) | 0.654 | |||
| <65 | 35 (35.7) | 27 (34.6) | 8 (40.0) | |
| ≥65 | 63 (64.3) | 51 (65.4) | 12 (60.0) | |
| Sex | 0.484 | |||
| Male | 62 (63.3) | 48 (61.5) | 14 (70.0) | |
| Female | 36 (36.7) | 30 (38.5) | 6 (30.0) | |
| Obstruction sign | 0.003* | |||
| No | 84 (85.7) | 71 (91.0) | 13 (65.0) | |
| Yes | 14 (14.3) | 7 (9.0) | 7 (35.0) | |
| Tumor stage | 0.621 | |||
| 0–II | 64 (65.3) | 50 (64.1) | 14 (70.0) | |
| III–IV | 34 (34.7) | 28 (35.9) | 6 (30.0) | |
| ASA physical status | 0.036* | |||
| I–II | 72 (73.5) | 61 (78.2) | 11 (55.0) | |
| III–IV | 26 (26.5) | 17 (21.8) | 9 (45.0) | |
| Operation type | 0.125 | |||
| Laparotomy | 14 (14.3) | 9 (11.5) | 5 (25.0) | |
| Laparoscopy | 84 (85.7) | 69 (88.5) | 15 (75.0) | |
| Tumor site | 0.774 | |||
| Colon | 73 (74.5) | 57 (73.1) | 16 (80.0) | |
| Rectum | 25 (25.5) | 21 (26.9) | 4 (20.0) | |
| Duration of operation (min) | 194.0±45.0 | 191.5±43.7 | 205.4±49.3 | 0.332 |
| Body composition | ||||
| TPAI | 0.728 | |||
| Normal | 84 (85.7) | 66 (84.6) | 18 (90.0) | |
| Sarcopenia | 14 (14.3) | 12 (15.4) | 2 (10.0) | |
| Body mass index (kg/m2) | 0.459 | |||
| <18.5 (Underweight) | 13 (13.3) | 12 (15.4) | 1 (5.0) | |
| 18.5–23 (Normal) | 31 (31.6) | 23 (29.5) | 8 (40.0) | |
| 23–25 (Overweight) | 14 (14.3) | 10 (12.8) | 4 (20.0) | |
| >25 (Obese) | 40 (40.8) | 33 (42.3) | 7 (35.0) | |
| Superficial fat area (HU) (n=77)a | 125.02±65.20 | 119.82±58.60 | 144.87±85.30 | 0.173 |
| Visceral fat area (HU) (n=77)a | 139.15±73.30 | 137.29±70.70 | 146.23±84.70 | 0.568 |
| Preoperative albumin (g/dL) (n=95)b | 3.91±0.51 | 3.93±0.51 | 3.82±0.53 | 0.369 |
| POD 1 albumin (g/dL) (n=92)c | 3.15±0.37 | 3.18±0.37 | 3.05±0.34 | 0.243 |
| Preoperative total protein (g/dL) (n=84)d | 6.90±0.63 | 6.90±0.66 | 6.87±0.53 | 0.666 |
| Systemic inflammatory response index | ||||
| POD 2 neutrophil count (cells/μL) (n=93)e | 7,511.83±293.70 | 7,215.41±319.02 | 8,666.32±676.46 | 0.050 |
| POD 2 lymphocyte count (cells/μL) (n=93)e | 1,244.09±48.00 | 1,283.92±52.71 | 1,088.95±109.21 | 0.219 |
| POD 2 CRP level (mg/L) (n=91)f | 120.20±5.99 | 112.34±5.93 | 155.86±14.83 | 0.023* |
| Preoperative lymphocyte count | 0.436 | |||
| Normal (>1,500 cells/μL) | 66 (67.3) | 54 (69.2) | 12 (60.0) | |
| Lymphopenia | 32 (32.7) | 24 (30.8) | 8 (40.0) |
Values are presented as number (%) or mean±standard deviation. Group A, patients with no complications; group B, patients with minor complications; and group C, patients with major complications. Group sizes differ across categories because of missing data.
ASA, American Society of Anesthesiologists; TPAI, total psoas area index; HU, Hounsfield unit; POD, postoperative day; CRP, C-reactive protein.
Group A, n=61; group B, n=16.
Group A, n=76; group B, n=19.
Group A, n=73; group B, n=19.
Group A, n=69; group B, n=15.
Group A, n=74; group B, n=19.
Group A, n=72; group B, n=19.
P<0.05.
A comparison of groups A+B and group C showed that the mean surgical duration was 261 minutes for group C and 194 minutes for group A+B, indicating a statistically significant difference (P=0.011) (Table 4).
Table 4.
Univariable analysis for groups A+B versus group C
| Variable | Total (n=109) | Groups A+B (n=98) | Group C (n=11) | P-value |
|---|---|---|---|---|
| Clinicopathologic factor | ||||
| Age (yr) | 0.966 | |||
| <65 | 39 (35.8) | 35 (35.7) | 4 (36.4) | |
| ≥65 | 70 (64.2) | 63 (64.3) | 7 (63.6) | |
| Sex | 0.743 | |||
| Male | 70 (64.2) | 62 (63.3) | 8 (72.7) | |
| Female | 39 (35.8) | 36 (36.7) | 3 (27.3) | |
| Obstruction sign | 0.373 | |||
| No | 92 (84.4) | 84 (85.7) | 8 (72.7) | |
| Yes | 17 (15.6) | 14 (14.3) | 3 (27.3) | |
| Tumor stage | 0.207 | |||
| 0–II | 69 (63.3) | 64 (65.3) | 5 (45.5) | |
| III–IV | 40 (36.7) | 34 (34.7) | 6 (54.5) | |
| ASA physical status | 0.288 | |||
| I–II | 78 (71.6) | 72 (73.5) | 6 (54.5) | |
| III–IV | 31 (28.4) | 26 (26.5) | 5 (45.5) | |
| Operation type | 0.082 | |||
| Laparotomy | 18 (16.5) | 14 (14.3) | 4 (36.4) | |
| Laparoscopy | 91 (83.5) | 84 (85.7) | 7 (63.6) | |
| Tumor site | 0.072 | |||
| Colon | 78 (71.6) | 73 (74.5) | 5 (45.5) | |
| Rectum | 31 (28.4) | 25 (25.5) | 6 (54.5) | |
| Duration of operation (min) | 201.0±54.5 | 194.0±45.0 | 261.0±89.7 | 0.011* |
| Body composition | ||||
| TPAI | 0.729 | |||
| Normal | 93 (85.3) | 84 (85.7) | 9 (81.8) | |
| Sarcopenia | 16 (14.7) | 14 (14.3) | 2 (18.2) | |
| Body mass index (kg/m2) | 0.776 | |||
| <18.5 (Underweight) | 15 (13.8) | 13 (13.3) | 2 (18.2) | |
| 18.5–23 (Normal) | 33 (30.3) | 31 (31.6) | 2 (18.2) | |
| 23–25 (Overweight) | 16 (14.7) | 14 (14.3) | 2 (18.2) | |
| >25 (Obese) | 45 (41.3) | 40 (40.8) | 5 (45.5) | |
| Superficial fat area (HU) (n=87)a | 124.72±64.66 | 125.02±65.20 | 122.38±63.80 | 0.847 |
| Visceral fat area (HU) (n=87)a | 135.17±72.76 | 139.15±73.30 | 104.57±63.80 | 0.164 |
| Preoperative albumin (g/dL) (n=105)b | 3.89±0.51 | 3.91±0.51 | 3.75±0.50 | 0.365 |
| POD 1 albumin (g/dL) (n=103)c | 3.16±0.36 | 3.15±0.37 | 3.20±0.31 | 0.717 |
| Preoperative total protein (g/dL) (n=92)d | 6.88±0.63 | 6.90±0.63 | 6.75±0.73 | 0.493 |
| Systemic inflammatory response index | ||||
| POD 2 neutrophil count (cells/μL) (n=104)e | 7,644.03±302.60 | 7,511.83±293.70 | 8,761.82±1,344.48 | 0.355 |
| POD 2 lymphocyte count (cells/μL) (n=104)e | 1,181.44±47.73 | 1,244.09±48.00 | 651.82±56.77 | <0.001* |
| POD 2 CRP level (mg/L) (n=102)f | 129.11±6.31 | 120.20±5.99 | 206.36±17.48 | <0.001* |
| Preoperative lymphocyte count | 0.053 | |||
| Normal (>1,500 cells/μL) | 70 (64.2) | 66 (67.3) | 4 (36.4) | |
| Lymphopenia | 39 (35.8) | 32 (32.7) | 7 (63.6) |
Values are presented as number (%) or mean±standard deviation. Group A, patients with no complications; group B, patients with minor complications; and group C, patients with major complications. Group sizes differ across categories because of missing data.
ASA, American Society of Anesthesiologists; TPAI, total psoas area index; HU, Hounsfield unit; POD, postoperative day; CRP, C-reactive protein.
Groups A+B, n=77; group C, n=10.
Groups A+B, n=95; group C, n=10.
Groups A+B, n=92; group C, n=11.
Groups A+B, n=84; group C n=8.
Groups A+B, n=93; group C, n=11.
Groups A+B, n=91; group C, n=11.
P<0.05.
Body composition
Sarcopenia was identified in 16 patients (14.7%), including 12 in group A, 2 in group B, and 2 in group C, based on TPAI. However, comparisons between groups A and B (P=0.728), groups A+B and group C (P=0.729), and group A and groups B+C (P=0.741) did not show statistically significant differences. The superficial fat area exhibited a higher mean value in group B than in groups A and C. However, this difference was not statistically significant between groups A and B (P=0.173), groups A+B and group C (P=0.847), and group A and groups B+C (P=0.314). The visceral fat area was lower in group C than that in groups A and B; however, this discrepancy was not statistically significant (groups A+B vs. group C, P=0.164; group A vs. groups B+C, P=0.763; group A vs. group B, P=0.568). Moreover, no statistically significant differences in preoperative total protein and albumin levels were observed among subgroups (Tables 2–4).
Neutrophil, lymphocyte, and CRP tests obtained before the surgical procedure and 2 days after
As illustrated in Fig. 1, there was a clear trend and significant P-value for neutrophil count, lymphocyte count, and CRP levels from POD 1 to 5. Neutrophil counts demonstrated a marked increase in values immediately following surgery across all 3 groups, accompanied by a gradual decline over time. Specifically, in the analysis between groups A and B, the levels remained significantly higher in group B on PODs 2, 4, and 5, with no differences on other days. In the comparison between groups A+B and group C, the levels were not significantly different preoperatively and postoperatively.
Fig. 1.
Postoperative trends of (A) neutrophil count, (B) lymphocyte count, and (C) C-reactive protein (CRP) level. Group A, patients with no complications; group B, patients with minor complications; and group C, patients with major complications. POD, postoperative day.
The lymphocyte counts significantly decreased following surgical intervention in all 3 groups, demonstrating a subsequent gradual recovery trajectory as the patients recuperated from the procedure. Comparative analysis of the data revealed that group A exhibited the highest mean values before and after surgery. Group B had the second-highest mean values, followed by group C. A statistically significant difference was observed between groups B and A on PODs 1, 3, and 5, with group B exhibiting lower mean values. Similarly, group C exhibited significantly lower mean values than groups A+B, both before and after the surgery.
CRP levels increased and subsequently decreased in all 3 groups postoperatively, with the highest levels observed in group C and the lowest in group A. This pattern was noted throughout the postoperative period, exhibiting statistically significant differences between groups A and B, and between groups A+B and group C on POD 2 (Tables 2, 3).
Selection of risk factors of postoperative complications
As presented in Table 5, the multivariable analysis revealed the factors that were significant in the univariable analysis between group A and groups B+C, group A and group B, and groups A+B and group C.
Table 5.
Multivariable analysis for complications
| Variable | OR (95% CI) | P-value |
|---|---|---|
| Group A vs. Groups B+C | ||
| Obstruction sign | 4.253 (1.238–14.607) | 0.021* |
| POD 2 lymphocyte count (cells/μL) | 0.998 (0.997–0.999) | 0.039* |
| POD 2 CRP level (mg/L) | 1.130 (1.030–1.239) | 0.009* |
| Group A vs. Group B | ||
| Obstruction sign | 4.532 (1.197–17.151) | 0.026* |
| ASA physical status III–IV | 2.440 (0.769–7.738) | 0.130 |
| POD 2 CRP level (mg/L) | 1.136 (1.011–1.239) | 0.012* |
| Groups A+B vs. Group C | ||
| Duration of operation (min) | 1.007 (0.996–1.019) | 0.205 |
| POD 2 lymphocyte count (cells/μL) | 0.997 (0.995–0.999) | 0.045* |
| POD 2 CRP level (mg/L) | 1.120 (0.972–1.290) | 0.118 |
Group A, patients with no complications; group B, patients with minor complications; and group C, patients with major complications.
OR, odds ratio; CI, confidence interval; POD, postoperative day; CRP, C-reactive protein; ASA, American Society of Anesthesiologists.
P<0.05.
Compared with no complications (group A), minor and major complications (groups B+C) were 4.25-fold more likely when preoperative intestinal obstruction symptoms were present and 1.13-fold more likely with higher postoperative day 2 CRP levels. In contrast, higher POD 2 lymphocyte count was associated with a lower risk of complications (OR, 0.998; 95% CI, 0.997–0.999).
Compared with no complications (group A), minor complications (group B) were 4 times more likely to occur when preoperative intestinal obstruction symptoms were present, and the risk increased by 1.13 times for each increase in postoperative day 2 CRP levels.
Compared with no or minor complications (groups A+B), higher postoperative day 2 lymphocyte count was associated with a lower likelihood of major complications (OR, 0.997; 95% CI, 0.995–0.999).
ROC analysis revealed the complications associated with lymphocyte count and CRP levels on POD 2
As illustrated in Fig. 2, ROC analysis was used to ascertain the complication cutoff for lymphocyte count and CRP levels on POD 2 between groups A and B+C, between groups A and B, and between groups A+B and C. Initially, the ROC analysis of complications occurrence for CRP levels on POD 2 revealed that CRP levels of 137.0 mg/L were associated with minor and major complications, 125.6 mg/L with minor complications (AUC, 0.706; P<0.001), and 137.0 mg/L with major complications (AUC, 0.860; P<0.001).
Fig. 2.
Receiver operating characteristic (ROC) curves and cutoff values for postoperative day (POD) 2 (A–C) C-reactive protein (CRP) levels and (D–F) lymphocyte counts between complications groups. (A, D) No complications (group A) versus minor (group B) and major complications (group C). (B, E) Group A versus group B. (C, F) Groups A+B versus group C. AUC, area under the curve; CI, confidence interval.
For lymphocyte counts, the ROC analysis of complications in group A and groups B+C indicated a cutoff of 905 cells/μL (AUC, 0.706; P=0.001). Moreover, the ROC analysis of complications in groups A+B and group C showed a statistically significant difference (AUC, 0.875; P<0.001). However, in groups A and B, the results of the ROC analysis were not statistically significant.
DISCUSSION
This study aimed to identify factors associated with the preoperative nutritional status and inflammation of patients with CRC that could be useful in selecting high-risk groups for postoperative complications. Consequently, the patients' body composition status and hematological parameters were comprehensively evaluated before and after surgery. Our findings indicated that minor complications were more likely when the diagnosis was accompanied by symptoms of obstruction and when the CRP levels exceeded 125.6 mg/L on POD 2. Conversely, major complications were more likely to occur when the absolute lymphocyte count was <905 cells/µL on POD 2.
The present study investigated various factors associated with postoperative complications in patients with CRC, spanning the trajectory from initial diagnosis to surgery. Traditionally, preoperative sarcopenia has been regarded as a critical risk factor for infectious complications and anastomotic leakage, largely attributed to compromised physiological reserves and weakened recovery mechanisms. However, emerging evidence challenges these conventional paradigms. For instance, Bajawi et al. [19] evaluated postoperative complications and mortality stratified by sarcopenia status, defined by the total skeletal muscle index and total skeletal muscle area per square meter at the L3 level, and reported no significant disparities between sarcopenic and nonsarcopenic cohorts. Furthermore, the deleterious impact of sarcopenia on functional recovery and long-term prognosis appears to be substantially mitigated by the widespread adoption of ERAS programs and advancements in laparoscopic techniques [20, 21]. While these findings suggest that sarcopenia may not significantly dictate the incidence of complications, the heterogeneity in diagnostic criteria across studies warrants cautious interpretation. Consequently, the relationship between sarcopenia and postoperative outcomes remains complex and necessitates further elucidation.
In the present analysis, patients presenting with bowel obstruction underwent preoperative bridging therapy utilizing self-expandable metal stent, followed by elective CRC surgery. Our findings corroborate the association between initial bowel obstruction and a significant increase in minor postoperative complications. To date, literature documenting an increased incidence of complications specifically in the context of preoperative bowel obstruction remains scarce, highlighting the need for further investigation.
Given that prolonged operative time inherently increases surgical stress, the elevation of CRP levels or the decrease in lymphocyte count on POD 2 could be interpreted as a physiological consequence of the extended procedure rather than a direct result of complications. To distinguish whether these changes were driven by surgical duration or complications, additional correlation analysis was performed. The results demonstrated that surgery duration had a positive correlation with CRP levels and a negative correlation with lymphocyte count, accounting for 41% and 35% of the variance, respectively. However, collinearity verification conducted during the risk assessment for major complications confirmed that this association was not statistically significant enough to confound the model. Furthermore, the remaining 60% to 70% of the variance could not be explained by operative time alone; this discrepancy likely elucidates why clinical outcomes vary even among patients undergoing the same surgery with similar procedure times.
Surgical stress elicits a complex, unavoidable neuroendocrine and immune response in all patients. Consequently, differentiating normal physiological recovery from pathological changes is a critical challenge. To address this, we analyzed daily acute-phase proteins and differential counts, utilizing the uncomplicated group as a baseline reference to account for the inherent surgical response. Under normal recovery, CRP typically rises within 6–8 hours, peaks at 24–48 hours, and normalizes by 10 to 14 days. Neutrophils peak on PODs 1–2, stabilizing by PODs 4–5, while lymphocyte counts reach a nadir on PODs 1–2 [22]. Existing literature reports varying timings for complication diagnosis, generally between PODs 1 and 7. While Straatman et al. [23] emphasized the importance of CRP decline by POD 3, Ramanathan et al. [24] demonstrated that absolute CRP levels on POD 2 (≥190 mg/L) were strongly predictive of infectious complications in CRC surgery. Similarly, Chiarelli et al. [25] validated lymphocyte count between 24 and 72 hours, preceding evident clinical symptoms, as a predictor of severe morbidity. In our study, we observed distinct hemodynamic trajectories starting from POD 2, even when accounting for the universal surgical stress response. While the uncomplicated group exhibited a moderate elevation in CRP followed by a decline after POD 3, the complication groups demonstrated a sharper initial rise on POD 2 and a failure to resolve in subsequent days. Specifically, in the minor complication group, CRP levels increased significantly on POD 2 and plateaued rather than declined. Regarding lymphocyte count, while the uncomplicated group showed a rebound after the initial nadir, the major complication group exhibited a deeper suppression on POD 2 and remained persistently low. We selected POD 2 as the primary time point for analysis because POD 1 is confounded by immediate hematologic instability, whereas POD 2 provides the earliest reliable distinction between normal and pathological responses (Fig. 1). Although POD 3 values may yield a statistically higher AUC, the clinical imperative for early prediction justifies using the distinct divergence observed at POD 2 as a standard for intervention. Our data suggests that even within the context of the surgical stress response, the significant stratification of biomarkers on POD 2 holds substantial clinical utility. Our established cutoffs (CRP 125.6 mg/L for minor complications, lymphocyte count 905 cells/µL for major complications) align with previous reports. Notably, lymphocyte count emerged as a critical predictor for major complications. Large-scale validation studies are required to confirm the utility of these cutoffs in routine clinical practice for CRC patients.
Composite inflammatory markers, such as neutrophil to lymphocyte ratio (NLR), lymphocyte to monocyte ratio (LMR), platelet to lymphocyte ratio (PLR), and systemic immune-inflammation index, have gained attention for their ability to characterize systemic inflammation and predict both short-term complications and long-term outcomes [26, 27]. However, in our cohort, these ratio-based indices (NLR, LMR, PLR) failed to demonstrate statistical significance. Instead, absolute lymphocyte count, the common denominator across these indices, emerged as a meaningful predictor on POD 2. This observation is supported by Patrascu et al. [11], who analyzed multiple immune markers using artificial neural networks to predict complications like anastomotic leakage. Their analysis revealed that lymphocytes were the critical common feature driving the predictive power of composite markers. Our results suggest distinct advantages of using lymphocyte count over composite markers. Clinically, lymphocyte count allows for rapid assessment without the need for additional calculation. More importantly, from a pathophysiological perspective, lymphocyte count serves as a direct indicator of stress-induced immunosuppression. By relying on absolute counts rather than ratios, this approach avoids the mathematical volatility often inherent in ratio-based indices, providing a more stable reflection of the patient's immune status.
We acknowledge several limitations in this study. First, the retrospective nature of the design implies that inherent selection biases cannot be entirely ruled out. Additionally, as this study was conducted at a single institution with a limited sample size, the generalizability of the results may be restricted. We attempted to minimize statistical bias through nonparametric analysis; however, the risk of overfitting remains a concern, particularly regarding the establishment of cutoff values for POD 2 biomarkers and the subsequent ROC analysis. Furthermore, our assessment of sarcopenia was limited to CT-based morphological evaluation. Current diagnostic criteria recommend incorporating functional metrics such as handgrip strength and gait speed, which were not available in this retrospective dataset. Lastly, although we identified lymphocyte count depression as a critical predictor of major complications, we did not evaluate specific lymphocyte subpopulations. Given the distinct immunological roles of Th1 and Th2 cells, future studies investigating these subsets are warranted to better understand the underlying mechanisms.
This study focused on identifying the most effective and useful factors in the selection of high-risk groups for postoperative complications, based on mandatory tests performed during CRC diagnosis and basic tests performed during surgery and recovery. Our findings indicate that CRP levels on POD 2 exhibited a predictive capacity for minor complications, whereas lymphocyte levels on the same day demonstrated a predictive capability for major complications. Therefore, it is crucial to respond promptly to changes in patient outcomes and to continue monitoring those with CRP levels >125.6 mg/L or lymphocyte count <905 cells/µL on POD 2. Additional prospective studies are warranted to investigate the prevention and early treatment of complications following CRC surgery.
Footnotes
Conflict of interest
No potential conflict of interest relevant to this article was reported.
Funding
This study was supported by grants from the Clinical Medicine Research Institute, Chosun University Hospital (2022).
Author contributions
Conceptualization: all authors; Data curation: MP; Formal analysis: MP, YK; Funding acquisition: KJK; Investigation: MP; Methodology: KJK; Project administration: KJK; Visualization: MP, YK; Writing–original draft: MP; Writing–review & editing: all authors. All authors read and approved the final manuscript.
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