Faculty of Human Medicine and Health Sciences, An-Najah National University, Palestine
Department of Pathology, An-Najah National University Hospital, Palestine
Department of Surgery, An-Najah National University Hospital, Palestine
Published Date: 09/08/2021.
*Corresponding author: AAdham Abu Taha, Faculty of Human Medicine and Health Sciences, Department of Pathology, An-Najah National University Hospital, Nablus, Palestine
Background: Patients with colorectal cancer suffer from impaired nutritional status, which has been a proven contributing factor of postoperative morbidity and mortality, especially surgical site infection (SSI). The current study was conducted to identify the risk factors for the development of surgical site infection in patients with colorectal cancer.
Methods: A prospective cohort study of 60 patients, who underwent colectomy for colorectal cancer, was performed in three tertiary care hospitals in Palestine starting from September 2017 until March 2019. Demographic and clinical information, as well as blood samples, were collected from patients before undergoing surgery. Patients were followed up for 30 days to assess for the development of surgical site infection. Risk factors for postoperative SSI were analyzed.
Results: The overall surgical site infection rate was 31.7 %. Factors associated with surgical site infection by univariate analysis were age > 60 (P < 0.001), lower educational level (P < 0.001), marital status, (P < 0.001), unemployment (P < 0.011), diabetes mellitus (P< 0.01), advanced stage of cancer (P< 0.004), lower concentration of albumin (P< 0.001) and lower concentration of prealbumin (P< 0.0001). The multivariate analysis using a binary logistic model showed that none of these variables was significant in the development of SSI.
Conclusion: The factors that were associated with surgical site infection among patients with colorectal cancer after surgery were lower educational level, marital status, unemployment, diabetes mellitus, advanced stages of cancer, and poor nutritional status as indicated by lower concentration of albumin and prealbumin. Interventions to improve nutritional status in these patients should focus more on patients with advanced stages of cancer and diabetes mellitus.
Keywords: Colorectal cancer; colectomy; surgical site infection; Prealbumin
Surgical site infection (SSI) is defined by the Centers for Disease Control and prevention (CDC) as an infection that involves the skin, subcutaneous tissue, and deep soft tissue (facial and muscle layers) where surgery occurred within 30 days after surgical intervention if no implant was left in place . Of all health care-associated infections, SSI is considered the most prevalent in developing countries, accounting for 29% of all infections  with great morbidity and mortality effects on patients. SSI was proved to increase hospital stay of the patient by 9.7 days, visits to the emergency department and readmission to the hospital with a cost of > 20,000$ per admission, the overall cost of SSI in the US was estimated to be 3.5$ - 10$ billion per year. Although long-term complications after SSI are not frequent, but 77% of deaths in patients with SSI are caused by the infection itself . The incidence rates of SSI among patients undergoing colorectal surgery (CRS) range from 3 to 26% [4,5]due to the clean-contaminated nature of the wound .
Identified risk factors for the development of postoperative SSI in patients with colorectal cancer after surgery include smoking, alcohol abuse, type 2 diabetes mellitus [7,8], obesity  and poor nutritional status [7,8,10].
Assessment of the nutritional status of patients preoperatively has been a major concern in the health departments since there is no one single tool that has validity to assess all patients regardless the type of surgery. The focus was on the use of patient's the patient’s BMI , preoperative weight loss , albumin  and lastly prealbumin . Colorectal cancer is the second most common cancer in Palestine with a prevalence of 9.4%, it’s also considered the second most frequent cancer death with a prevalence measuring 12.4% . Patients with CRC are more likely to suffer from poor nutritional status that would have an adverse effect on the healing process after surgery. In Palestine, no data on SSIs after CRS have been reported to date. Herein, we conducted an SSI surveillance study after CRS in a prospective multicenter design in Palestine. The objectives of this study were to 1) evaluate the incidence of SSI after colorectal surgery; 2) identify the risk factors for the development.
Study design and setting
A prospective cohort study was conducted in three tertiary care hospitals in Palestine from September 2017 until March 2019. Two hospitals are located in the city of Nablus: An-Najah National University hospital (NNUH) and Rafedia Surgical Governmental Hospital (RSGH), and the third hospital is located in Ramallah: Palestine Medical Complex (PMC).
Inclusion and exclusion criteria
All colorectal cancer patients undergoing open resection at the participating hospitals during the period of study (2017 – 2019) were included with a total number of 60 patients. Inclusion criteria included adult patients with colorectal cancer stage 1, 2, and 3 with complete colonoscopy and biopsy, chest X-ray, liver ultrasound, computed tomography, and magnetic resonance imaging. Patients on chemotherapy before undergoing resection or with ongoing infection were excluded from the study.
Sample size and sampling techniques
The Raosoft sample size calculator was used for sample size calculation. (http://www.raosoft.com/samplesize.html) Furthermore, we used 9% prevalence of colorectal cancer, 5% margin of error at 95% confidence interval as recommended. Sampling technique was voluntary response sampling.
Approvals were obtained from the Institutional Review Board (IRB) of An-Najah National University and the Palestine Ministry of Health. Verbal consent was obtained from all participating patients.
A serum sample was collected from each colorectal cancer patient undergoing resection; samples were stored at - 80 °C until analyzed for prealbumin by Immunoturbidimetric assay on Roche Cobas C501 (Roche Diagnostics, Germany). Patients were divided into three groups according to their prealbumin level: group 1 (low prealbumin < 20 mg/dL), group 2 (normal prealbumin 20-40 mg/dL), and group 3 (high prealbumin > 40 mg/dL). After surgery, patients were followed up for 30 days in both the surgical department and outpatient clinics, and evaluation of the surgical wound was done using Clavien-Dindo classification, grades of 2 or more were taken into consideration, then data was entered and analyzed using the IBM Statistical Package for Social Sciences program version 21 (IBM Corporation, Chicago, Illinois).
Continuous variables were analyzed utilizing the unpaired Student's t-test and the Mann–Whitney U test. Categorical variables were analyzed with Chi-square analysis. Univariate and multivariate analyses were performed. In all cases, P < 0.05 was considered statistically significant. All statistical analysis was performed using SPSS V21.0 (IBM Corporation, Chicago, Illinois).
Table 1: Socio-demographic and clinical characteristics of the study sample
Table 2: Predictors of SSI among the study sample.
Sociodemographic and clinical characteristics of the enrolled patients
The sociodemographic and clinical characteristics of the enrolled patients are shown in Table 1. The mean age of the enrolled patients was 60 +12.34 years, more than half (56.7%) of them were older than 60 years. The majority of patients were males (36, 60%), married (48, 80%), living in the city (35, 58.3%), unemployed (32, 53.3%), and low monthly household income (less than 2000 New Israeli Shekel (NIS)) (27, 45%). Most patients were college graduates (25, 41.7 %).
Fourteen patients (23.3%) were from Rafedia Governmental Hospital, 17 (28.3%) patients were from An-Najah National University Hospital and 29 (48.3%) patients were from Palestine Medical Complex Hospital. Most patients did not have diabetes mellitus 45 (75%), most patients 31 (51.7%) reported a positive family history for colorectal cancer and half of them were smokers. Most patients 27 (45%) have stage 2 colorectal cancer.
Characteristics of the patients with SSI:
Table 2 compares the characteristics of patients with and without SSI. Nineteen (31.7%) patients were reported to have surgical site infection within 30 days postoperatively, according to clavien-dindo score 15 (78.9 %) of those who had SSI has grade 2 and 4 (21.1 %) has grade 3. More than half of the infected patients (57.9%) were males, 17 (89.5%) were elderly, 12 (63.2%) lived in the cities, more than half (10, 52.6%) were married, most of them (15, 78.9%) were unemployed, and the majority (14, 73.7%) had low monthly income. Eight (42.1%) came from PMC, 6 (31.6%) from NNUH, and five (26.3%) came from RSGH. More than two thirds (13, 68.4%) had no history of colorectal cancer. The majority of the infected patients (18, 94.8%) had stage two and 3 CRC. Concerning the nutritional status, 15 (78.9%) patients with SSI had low albumin and all (100%) infected patients had low prealbumin levels.
Univariate and multivariate analyses of sociodemographic and clinical characteristics
Univariate and multivariate analyses were used to assess the related sociodemographic and clinical characteristics (Table 2). The univariate analysis showed that age > 60 (P < 0.001), lower educational level (P < 0.001 ), being a single, divorced or widowed (P < 0.001 ), unemployment ( P < 0.011 ), having Diabetes Mellitus (P < 0.01 ), advanced stage of cancer (P < 0.004 ), lower concentration of albumin (P < 0.0001 ) and lower concentration of prealbumin (P< 0.0001 ) were significant predictive factors for postoperative surgical site infection. Multivariate analysis using binary logistic model showed that none of the variables was a significant predictor for the development of SSI.
In our study, we assessed the incidence of SSI and analyzed the risk factors associated with the development of SSI among colorectal cancer patients who are undergoing resection in Palestine. Clavien-Dindo classification, a universally accepted system for grading complications [15,16], was used in our study for the assessment and grading of postoperative SSI in patients with colorectal cancer. Surgical site infections (SSIs) are the leading cause of postoperative infectious complications after colectomy, thus they prolong hospital stay and increase the health care cost due to readmission to the hospital. Moreover, they sometimes result in death even during the hospital stay [10,17,18] Globally, the incidence of SSI after CRS ranges from 2.4% to 21.6%. The incidence rate in our study (31.7%) was higher than China (7.1%)(17), Japan (17.8%) (5), the US (5.1%) (18), Spain (24.3%) , Israel (22.2%) , and Saudi Arabia (30%) .
Among the identified risk factors for the development of SSI were age > 60 (P < 0.001), lower educational level (P < 0.001), being a single, divorced or widowed (P < 0.001), unemployment (P < 0.011), having diabetes mellitus (P < 0.01), advanced stage of cancer (P < 0.004), lower concentration of albumin (P < 0.0001) and lower concentration of prealbumin (P< 0.0001). These findings are in agreement with a report from Saudi Arabia, where Hibbert et al. concluded that the preoperative nutritional status of patients and obesity are associated with the development of SSI. In a study conducted in Japan in 2014 . Watanabi et al. reported obesity and Incision contamination as risk factors for the development of SSI.
Pre-operative anemia, history of neoadjuvant chemotherapy and longer surgical duration were identified by Lei et al. in 2020  as risk factors for SSI. Patients with colorectal cancer are at higher risk for malnutrition, developing an imbalance between nutritional and inflammatory status and thus developing infectious complications after surgery . Recently, a growing interest has focused on using prealbumin and albumin to assess the nutritional status of patients before undergoing colectomy. Studies have shown prealbumin to be a useful marker for predicting morbidity and mortality in hemodialysis patients , after spinal surgery [26-28], and in patients undergoing radiotherapy for head and neck cancer . Moreover, prealbumin has been shown to be a good predictor of morbidity and mortality in cardiac surgery , left ventricular assist device implantation  and heart failure , after gastrectomy , after hip fracture in geriatric  and predictor for early recurrence of lung cancer .
Based on the results of the current study, prealbumin appears to be a better predictor of SSI after colectomy. Because prealbumin has a short half-life of 2 days, it reflects recent rather than overall nutritional status and can be used to detect early nutritional deficits. We hypothesize that if we can provide potential intervention with nutritional support before surgery, low preoperative prealbumin concentrations may be a modifiable risk factor for postoperative morbidity.Low albumin concentrations (less than 3.5 mg/dl) can be used as a risk factor for the development of SSI, which is similar to the results found in other studies . A retrospective study of 3732 patients with colorectal cancer undergoing surgery at Chang Gung Memorial Hospital by Cheng-Chou et al. showed that patients with lower concentrations of albumin were at higher risk for developing short-and long-term complications after surgery . A prospective study by Jonathan et al. collected data from medical registries in North and Central Denmark (with approximately 2.15 million inhabitants) from 1 January 1997 to 31 December 2011 had shown similar results . Another prospective, observational study was conducted in three centers from November 2011 to April 2014 by Luigi De et al., Hypoalbuminemia was found to be significantly associated with postoperative infectious complications .
In agreement with previous reports about age, our results showed advanced age (more than 60) was significantly associated with the development of SSI [9,10,38]. Our study showed that patients with a history of diabetes mellitus were more likely to development of SSI after colectomy; which is not a surprise as other previous studies had shown similar results ; these studies suggest that diabetic patients undergoing colectomy should have their blood glucose tightly controlled before surgery [40,41]. People with advanced stages of cancer were more likely to have SSI. Shaffer et al. , and Banaszkiewicz et al.  reported similar findings.
Limitations of Study
Despite the fact that this study was conducted in the three major hospitals in Palestine, the sample size is still small. Moreover, not all patients admitted to these hospitals met the inclusion criteria.
The factors that were associated with surgical site infection among patients with colorectal cancer after surgery were lower educational level, marital status, unemployment, diabetes mellitus, advanced stages of cancer, and poor nutritional status as indicated by lower concentration of albumin and prealbumin. Interventions to improve nutritional status in these patients should focus more on patients with advanced stages of cancer and diabetes mellitus.
Data are available on request by contacting the corresponding authors.
Conflicts of Interest
The author(s) declare(s) that there is no conflict of interest regarding the publication of this paper.
This project was funded by An-Najah National University.