Wenjie Cai1, Lina Wang1, Weiqiong Wang2, Ting Zhou1. 1. Department of General Surgery, The First Affiliated Hospital of Hainan Medical University, Haikou, China. 2. Institute of Internal Nursing Teaching and Researching, School of Nursing, Guangdong Medical University, Dongguan, China.
Abstract
Background: Surgical site infection (SSI) influenced the result of surgical treatment, which was known as the second most prevalent hospital-based infection. But, the factors of SSI are not uniform. The purpose of this study was to identify the risk factors of SSI in patients with colorectal cancer. We conducted a meta-analysis of epidemiological research to provide a scientific basis for the prevention of SSI. Methods: The PubMed, Medline, Embase, China National Knowledge Infrastructure (CNKI), and Wanfang databases were independently searched by 2 researchers to identify all relevant studies. Studies were selected if they met the selection criteria, which was defined according to the PICOS principles. The quality of the evidence was assessed using Egger's P value, study heterogeneity, and sample size. Studies were categorized into 3 groups as follows: low quality (Class 4), moderate quality (Class 2/3), and high quality (Class 1). The meta-analysis was performed using RevMan 5.3 software. Results: A total of 17 studies involving 61,611 patients were included in the meta-analysis. The results identified 7 patient-related risk factors of SSI, including male gender, obesity, diabetes mellitus, American Society of Anesthesiologists (ASA) score, cigarette smoking, tumor location, and serum albumin level, and 5 treatment-related risk factors, including laparoscopic surgery, operation time, blood loss, blood transfusion, and abdominal surgical history. Age was not directly related to SSI in colorectal cancer. Conclusions: It is possible that patients can be treated effectively by identifying these factors of SSI. 2022 Translational Cancer Research. All rights reserved.
Background: Surgical site infection (SSI) influenced the result of surgical treatment, which was known as the second most prevalent hospital-based infection. But, the factors of SSI are not uniform. The purpose of this study was to identify the risk factors of SSI in patients with colorectal cancer. We conducted a meta-analysis of epidemiological research to provide a scientific basis for the prevention of SSI. Methods: The PubMed, Medline, Embase, China National Knowledge Infrastructure (CNKI), and Wanfang databases were independently searched by 2 researchers to identify all relevant studies. Studies were selected if they met the selection criteria, which was defined according to the PICOS principles. The quality of the evidence was assessed using Egger's P value, study heterogeneity, and sample size. Studies were categorized into 3 groups as follows: low quality (Class 4), moderate quality (Class 2/3), and high quality (Class 1). The meta-analysis was performed using RevMan 5.3 software. Results: A total of 17 studies involving 61,611 patients were included in the meta-analysis. The results identified 7 patient-related risk factors of SSI, including male gender, obesity, diabetes mellitus, American Society of Anesthesiologists (ASA) score, cigarette smoking, tumor location, and serum albumin level, and 5 treatment-related risk factors, including laparoscopic surgery, operation time, blood loss, blood transfusion, and abdominal surgical history. Age was not directly related to SSI in colorectal cancer. Conclusions: It is possible that patients can be treated effectively by identifying these factors of SSI. 2022 Translational Cancer Research. All rights reserved.
Entities:
Keywords:
Colorectal cancer; meta-analysis; risk factors; surgical site infection (SSI)
Surgical site infection (SSI) (1-3) refers to an infection occurring at or near a surgical incision within 30 days of an operation or 1 year of the implantation of a foreign body. SSIs can be classified into 3 types: superficial incisional infection, deep incisional infection, and organ/space infection. The incidence rate of SSI differs according to the type of surgery, and studies have reported that the incidence of SSI in colorectal cancer surgery is between 23% and 26% (4,5).Colorectal cancer is a common gastrointestinal tumor (6). In 2012, colorectal cancer ranked third for incidence among men and second among women, with approximately 1.4 million new cases and about 690,000 deaths, making it the fourth most deadly cancer worldwide (7). In recent years, the incidence and mortality rates of colorectal cancer in China have increased alongside accelerating economic development and urbanization and the changing dietary structure and living habits of residents (7). In 2012, the incidence and mortality rates of colorectal cancer in China were 0.83 times and 0.88 times that of the world and 1.03 times and 1.02 times that of Asian countries, respectively, with colorectal cancer ranking second among malignant tumors of the digestive system (7).Surgery is the most important treatment for colorectal cancer, with nearly 90% of colorectal cancer patients receiving tumor resection. As a common postoperative complication of colorectal cancer surgery, SSI can seriously impact surgical quality and patient safety. One study found that patients with local disease were more likely to gain incisional infection, while patients with severe disease were more likely to gain organ/space infection (8), which can develop into systemic infection, septic shock, or multiple organ dysfunction syndrome. The high incidence of SSIs after colorectal cancer surgery has been increasingly recognized (9). Therefore, it is necessary to identify risk factors of SSI in colorectal cancer so that effective measures can be taken to reduce the incidence of postoperative infection among high-risk groups (9).The occurrence of SSI in patients undergoing colorectal cancer surgery is influenced by many factors, including patient-related factors [age, obesity, diabetes mellitus, American Society of Anesthesiologists (ASA) score, cigarette smoking, tumor location, and serum albumin level], treatment-related factors (laparoscopic surgery, operation time, blood loss, blood transfusion, and abdominal surgical history), and medical environment–related factors (operating room ventilation, hand hygiene of medical staff, and disinfection of medical instruments) (10). Unsatisfactorily, few risk factors are generally accepted and some findings on these factors in medical literature are often contradictory.The purpose of this study was to explore the risk factors of postoperative SSI in patients with colorectal cancer and to provide a scientific basis for the formulation of preventive measures against SSI. We present the following article in accordance with the MOOSE reporting checklist (available at https://tcr.amegroups.com/article/view/10.21037/tcr-22-627/rc) (11).
Methods
Publication search
The PubMed, Medline, Embase, China National Knowledge Infrastructure (CNKI), and Wanfang databases were searched from inception to 2021 by 2 reviewers. All literature in the databases was searched without language restrictions. The search terms were as follows: (“Colorectal, rectal, colon, or colorectal cancer”); (“colon, surgical infection, risk, or site”); (“colorectal tumor, site infection, risk factors, or wound infection”); (“colon, infection, risk factors, or wound infection”); (“colorectal cancer, surgery, wound infection, or risk”). The reference list of each included study was also explored to identify other high-quality research.
Selection of studies
The inclusion criteria were formulated based on the PICOS (population, intervention, comparator, outcomes, and study design) framework (12). These criteria were as follows: patients had undergone colorectal surgery; relevant interventions were performed on patients; the incidence of risk factors was shown by odds ratios (ORs) or relative risks (RRs) with corresponding 95% confidence intervals (CIs); and the studies were case-control or cohort studies.The following types of literature were excluded: reviews, study protocols, letters, conference abstracts, unpublished papers, animal experiments, and studies with insufficient data.
Data extraction and quality assessment
The 2 investigators independently performed the data extraction according to pre-agreed criteria. When there was a disagreement, this was resolved through discussion with a third investigator. The ORs and corresponding 95% CIs were chosen for analysis in this review. Cross-sectional studies on the prevalence and associated factors of SSI were excluded, because of the small sample number. The data extracted from each study were as follows: the first author, year of publication, country, recruitment period, sample size, type of SSI, study type, location of tumor, risk factors, and Newcastle-Ottawa scale (NOS) score (13).The quality assessment was performed according to the 3 dimensions of NOS: (I) selection of study groups; (II) intercomparability of the study; and (III) outcomes (14). The highest NOS score is 9 stars, and studies scoring 7 stars were considered to be of high quality (13). The relevant results are shown in . In addition, the strength of the evidence was assessed using the following 3 indicators: (I) a total sample size of more than 1000; (II) intergroup inconsistency (I2) of less than 50%; and (III) an Egger’s P value of more than 0.1 (). Studies were considered to have high-quality evidence when they satisfied all 3 indicators (Class 1), moderate-quality evidence when they satisfied 2 indicators (Class 2) or 1 indicator (Class 3), and low-quality evidence when they satisfied none of the indicators (Class 4).
Table 1
The quality assessment of included studies by the NOS
Study
Selection
Comparability
Outcome
Total
Representativeness of the exposed cohort
Selection of the non-exposed cohort
Ascertainment of exposure
Demonstration that outcome of interest was not present at start of study
Comparability of cohorts on the basis of the design or analysis
Assessment of outcome
Was follow-up long enough for outcomes to occur
Adequacy of follow up of cohorts
Yu Tang 2020
1
1
1
1
1
1
1
1
8
Jung Wook Huh 2019
1
1
1
1
1
1
1
7
Takatoshi Nakamura 2016
1
1
1
1
1
1
1
7
Toshimichi Tanaka 2017
1
1
1
1
1
1
1
1
8
Joseph Drosdeck 2013
1
1
1
1
1
1
1
1
8
Kenji Katsumata 2021
1
1
1
1
1
1
1
7
Keita Itatsu 2014
1
1
1
1
1
1
1
7
Takatoshi Nakamura 2020
1
1
1
1
1
1
1
1
8
Thibault Crombe 2016
1
1
1
1
1
1
1
7
Chikao Miki 2006
1
1
1
1
1
1
1
7
Sam E. Mason 2017
1
1
1
1
1
1
1
7
Avinash Bhakta 2016
1
1
1
1
1
1
1
7
Marta Silvestri 2018
1
1
1
1
1
1
1
7
Wick EC 2011
1
1
1
1
1
1
1
7
Masanori Watanabe 2015
1
1
1
1
1
1
1
1
8
Mary R. Kwaan 2013
1
1
1
1
1
1
1
7
Tolga Olmez 2020
1
1
1
1
1
1
1
7
NOS, Newcastle Ottawa scale.
Table 2
Risk factors of SSIs in patients undergoing CRS
Significant factors
No. of studies
No. of patients
I2 (%)
PBegg-Mazumdar’S
OR (95% CI)
Evidence grading
Male gender
10
55,706
28
0.19
1.20 (1.08, 1.35)
Class 1
Obesity
12
58,648
94
<0.0001
1.38 (1.20, 1.60)
Class 3
Diabetes mellitus
8
48,804
0
0.43
1.58 (1.44, 1.72)
Class 1
ASA score
6
6,111
0
0.78
1.72 (1.39, 2.12)
Class 1
Laparoscopic surgery
3
2,608
42
0.18
1.95 (1.20, 3.16)
Class 1
Cigarette smoking
5
44,588
0
0.77
1.35 (1.28, 1.43)
Class 1
Operation time
9
49,624
69
0.001
2.05 (1.61, 2.59)
Class 3
Age
10
56,525
83
0.36
0.98 (0.93, 1.03)
Class 2
Blood loss
3
926
80
0.007
1.38 (0.72, 2.66)
Class 4
Blood transfusion
4
4,993
0
0.56
2.02 (1.48, 2.77)
Class 1
Tumor location
4
4,770
66
0.03
1.16 (0.72, 1.86)
Class 3
Serum albumin
3
2,263
0
0.91
3.36 (2.25, 5.02)
Class 1
Ostomy formation
3
1,328
0
0.56
0.74 (0.50, 1.11)
Class 1
Abdominal surgical history
3
1,849
0
0.46
1.64 (1.18, 2.28)
Class 1
SSIs, surgical site infections; CRS, colorectal Surgical; P value, probability value; 95% CI, 95% confidence interval; OR, odds ratio; ASA, American Society of Anesthesiologists.
NOS, Newcastle Ottawa scale.SSIs, surgical site infections; CRS, colorectal Surgical; P value, probability value; 95% CI, 95% confidence interval; OR, odds ratio; ASA, American Society of Anesthesiologists.
Statistical analysis
Statistical analyses were conducted by 2 investigators using RevMan version 5.3 (Cochrane, London, UK). The summary ORs and 95% CIs of the studies were analyzed using the DerSimonian-Laird random-effects model. OR values of the same factor from different studies were directly pooled when the P value was less than 0.05. The intergroup heterogeneity of each study was evaluated according to Cochran’s Q (χ2) test, which was quantified with the I2 statistic. Heterogeneity was assessed using 3 risk levels based on the I2 value (low I2<50%, moderate I2=50–74%, and high I2>75%). A sensitivity analysis was performed, and the effect model was changed to identify potential sources of heterogeneities. Publication bias was evaluated using funnel plots, and funnel plot asymmetry was further corrected using the trim and fill method.
Results
Study characteristics
A total of 1,189 studies were retrieved from the databases and screened independently by 2 investigators. A total of 986 references remained after exclusion of duplicates. A further 534 studies were excluded after reading the topics or abstracts. Finally, 17 studies (10,14-29) were enrolled in this meta-analysis after a full-text review by the 2 investigators. The patients in the included studies had undergone colorectal cancer surgery, and the risk factors of SSI were included in each study. The relevant baseline characteristics of the patients in the included studies are shown in . The process of literature retrieval is detailed in .
Table 3
General characteristics of included studies
Author
Nation
Recruited period
Number of patients
Type of SSI
Study type
Location of tumors
Risk factors
Yu Tang 2020
China
April 2015–May 2017
326
SSIs
Cohort study
Colorectal cancer
12, 24
Jung Wook Huh 2019
South Korea
January 2009 to December 2011
3575
SSIs
Cohort study
Colorectal cancer
1, 2, 3, 4, 7, 8, 10, 11, 15, 16
Takatoshi Nakamura 2016
Japan
January 2010 through April 2015
670
SSIs
Cohort study
Colon cancer
4, 17
Toshimichi Tanaka 2017
Japan
January 1, 2012 to December 31, 2013
432
SSIs
Cohort study
Colorectal cancer
1, 2, 3, 4, 7, 8, 9, 10, 15, 18, 19, 20
Joseph Drosdeck 2013
USA
January 2006 and October 2012
419
SSIs
Cohort study
Laparoscopic colon resections
1, 2, 3, 5, 6, 8, 12, 21, 22, 23, 24, 25, 26
Kenji Katsumata 2021
Japan
–
701
SSIs
Cohort study
Rectal cancer
1, 2, 7, 8, 10, 11
Keita Itatsu 2014
Japan
November 2009–February 2011
1,980
I-SSI
Cohort study
Colorectal cancer
25, 27, 28
Takatoshi Nakamura 2020
Japan
January 2010–December 2017
1,144
SSIs
Cohort study
Colon cancer
18
Thibault Crombe 2016
France
2004–2013
1,104
SSIs
Cohort study
Colorectal cancer
2, 3, 6, 7, 8, 12
Chikao Miki 2006
Japan
–
285
SSIs
Cohort study
Colorectal cancer
1, 9, 10, 11, 30
Sam E. Mason 2017
UK
September 2012–July 2014
246
SSIs
Cohort study
Colorectal cancer
1, 2, 3, 6, 8, 29, 31, 32
Avinash Bhakta 2016
USA
2008–2012
42,132
SSIs
Cohort study
Colorectal cancer
1, 2, 3, 6, 8, 33
Marta Silvestri 2018
Italy
June, 2010–July, 2014
687
SSIs
Cohort study
Colorectal cancer
1, 2, 3, 4, 6, 7, 8, 17, 18, 19
Wick EC 2011
Maryland
January 1, 2002–December 31, 2008
7,020
SSIs
Cohort study
Colon cancer, diverticulitis, or inflammatory bowel disease
1, 2, 8
Masanori Watanabe 2015
Japan
2005–2010
538
SSIs
Cohort study
Colorectal cancer
4
Mary R. Kwaan 2013
Canada
2008–2009
143
SSIs
Cohort study
Colorectal cancer
2, 14
Tolga Olmez 2020
Turkey
January 2013–July 2019
209
SSIs
Cohort study
Colorectal cancer
1, 2, 3, 4, 5, 9, 11, 13, 19
1. male gender; 2. obesity (BMI >30 kg/m2); 3. diabetes mellitus; 4. ASA score ≥3; 5. laparoscopic surgery; 6. cigarette smoking; 7. operation time (≥180 min); 8. age ≥65 years; 9. estimated blood loss ≥100 mL); 10. blood transfusion; 11. tumor location; 12. abdominal surgical history; 13. peri-operative immunonutrition (no/yes); 14. midpoint from umbilicus to pubis; 15. clinical stage; 16. tumor size; 17. pre-hemoglobin >10 g/dL; 18. serum albumin, <2.5 g/dL; 19. ostomy formation; 20. blood flow preservation; 21. hand assistance; 22. Pfannenstiel incision; 23. prior open abdominal surgery; 24. history of COPD; 25. immunosuppressants; 26. postoperative chemotherapy; 27. chronic liver disease; 28. wound length; 29. wound classification; 30. concomitant medical problems; 31. conversion to open approach; 32. use of conditioned CO2; 33. radiation. SSI, surgical site infection; I-SSI, incisional surgical site infection; BMI, body mass index; ASA, American Society of Anesthesiologists; COPD, chronic obstructive pulmonary disease.
Figure 1
The flowchart of included studies.
1. male gender; 2. obesity (BMI >30 kg/m2); 3. diabetes mellitus; 4. ASA score ≥3; 5. laparoscopic surgery; 6. cigarette smoking; 7. operation time (≥180 min); 8. age ≥65 years; 9. estimated blood loss ≥100 mL); 10. blood transfusion; 11. tumor location; 12. abdominal surgical history; 13. peri-operative immunonutrition (no/yes); 14. midpoint from umbilicus to pubis; 15. clinical stage; 16. tumor size; 17. pre-hemoglobin >10 g/dL; 18. serum albumin, <2.5 g/dL; 19. ostomy formation; 20. blood flow preservation; 21. hand assistance; 22. Pfannenstiel incision; 23. prior open abdominal surgery; 24. history of COPD; 25. immunosuppressants; 26. postoperative chemotherapy; 27. chronic liver disease; 28. wound length; 29. wound classification; 30. concomitant medical problems; 31. conversion to open approach; 32. use of conditioned CO2; 33. radiation. SSI, surgical site infection; I-SSI, incisional surgical site infection; BMI, body mass index; ASA, American Society of Anesthesiologists; COPD, chronic obstructive pulmonary disease.The flowchart of included studies.
Risk factors of SSI
A total of 33 risk factors were identified from the 17 included studies (10,14-29). Among these risk factors, 14 were reported in at least 3 studies (), and 19 were mentioned in fewer than 3 studies. To avoid bias in the results, only the 14 risk factors with a high incidence were selected in this study, and there was no further analysis of the other 19 risk factors, of which the sample size was too small. The 14 selected risk factors were divided into patient-related risk factors and treatment-related risk factors.
Patient-related risk factors
Male gender
Male gender was reported in 10 of the 17 included studies (15,17-19,21,22,24,25,27,29). The results revealed a strong correlation between male gender and SSIs (OR =1.20, 95% CI: 1.08–1.35, I2=28%; ).
Figure 2
The forest plot showed the relationship between male gender and the risk of SSI. 95% CI, 95% confidence interval; P value, probability value; IV, Inverse Variance methods; SE, standard error; SSI, surgical site infection.
The forest plot showed the relationship between male gender and the risk of SSI. 95% CI, 95% confidence interval; P value, probability value; IV, Inverse Variance methods; SE, standard error; SSI, surgical site infection.
Obesity
Following the World Health Organization (WHO) classification, we defined obesity as a BMI over 30 kg/m2. A total of 12 studies (10,15,17-22,24,25,27,30) found that patients with obesity may have a high risk of SSIs (OR =1.38, 95% CI: 1.20–1.60, I2=94%; ).
Figure 3
The forest plot showed the relationship between obesity and the risk of SSI. 95% CI, 95% confidence interval; P value, probability value; IV, Inverse Variance methods; SE, standard error; SSI, surgical site infection.
The forest plot showed the relationship between obesity and the risk of SSI. 95% CI, 95% confidence interval; P value, probability value; IV, Inverse Variance methods; SE, standard error; SSI, surgical site infection.
Diabetes mellitus
Eight studies (15-18,21,24,25,27) reported data suggesting that diabetes mellitus may influence SSI incidence. From these results, we concluded that there was a significant positive relationship between diabetes mellitus and SSIs (OR =1.58, 95% CI: 1.44–1.72, I2=0%; ).
Figure 4
The forest plot showed the relationship between diabetes mellitus and the risk of SSI. 95% CI, 95% confidence interval; P value, probability value; IV, Inverse Variance methods; SE, standard error; SSI, surgical site infection.
The forest plot showed the relationship between diabetes mellitus and the risk of SSI. 95% CI, 95% confidence interval; P value, probability value; IV, Inverse Variance methods; SE, standard error; SSI, surgical site infection.
ASA score
Six studies (18,23-25,27,29) reported the ASA score of patients. An ASA score of more than 3 was related to a risk of SSIs (OR =1.72, 95% CI: 1.39–2.12, I2=0%; ).
Figure 5
The forest plot showed the relationship between ASA score and the risk of SSI. 95% CI, 95% confidence interval; P value, probability value; IV, Inverse Variance methods; SE, standard error; ASA, American Society of Anaesthesiologists; SSI, surgical site infection.
The forest plot showed the relationship between ASA score and the risk of SSI. 95% CI, 95% confidence interval; P value, probability value; IV, Inverse Variance methods; SE, standard error; ASA, American Society of Anaesthesiologists; SSI, surgical site infection.
Cigarette smoking
The data of 5 studies (15-17,21,25) reported a significant relationship between cigarette smoking and SSIs when comparing smoking and non-smoking patients (OR =1.35, 95% CI: 1.28–1.43, I2=0%; ).
Figure 6
The forest plot showed the relationship between cigarette smoking and the risk of SSI. 95% CI, 95% confidence interval; P value, probability value; IV, Inverse Variance methods; SE, standard error; SSI, surgical site infection.
The forest plot showed the relationship between cigarette smoking and the risk of SSI. 95% CI, 95% confidence interval; P value, probability value; IV, Inverse Variance methods; SE, standard error; SSI, surgical site infection.
Serum albumin
A meta-analysis of 3 studies (23,25,27) investigated the influence of serum albumin. The results showed that there was a high risk of SSIs when the serum albumin level of patients was over 2.5 g/dL (OR =3.36, 95% CI: 2.25–5.02, I2=0%; ).
Figure 7
The forest plot showed the relationship between serum albumin and the risk of SSI. 95% CI, 95% confidence interval; P value, probability value; IV, Inverse Variance methods; SE, standard error; SSI, surgical site infection.
The forest plot showed the relationship between serum albumin and the risk of SSI. 95% CI, 95% confidence interval; P value, probability value; IV, Inverse Variance methods; SE, standard error; SSI, surgical site infection.
Tumor location
Four studies (18,19,22,24) reported that tumor location was related to the risk of SSIs (OR =1.16, 95% CI: 0.72–1.86, I2=66%; ).
Figure 8
The forest plot showed the relationship between tumor location and the risk of SSI. 95% CI, 95% confidence interval; P value, probability value; IV, Inverse Variance methods; SE, standard error; SSI, surgical site infection.
The forest plot showed the relationship between tumor location and the risk of SSI. 95% CI, 95% confidence interval; P value, probability value; IV, Inverse Variance methods; SE, standard error; SSI, surgical site infection.
Age
Patient age was not directly related to SSI in colorectal cancer (OR =0.98, 95% CI: 0.93–1.03, I2=83%; ) in the included studies (15-19,21,24,25,27,29).
Figure 9
The forest plot showed the relationship between age and the risk of SSI. 95% CI, 95% confidence interval; P value, probability value; IV, Inverse Variance methods; SE, standard error; SSI, surgical site infection.
The forest plot showed the relationship between age and the risk of SSI. 95% CI, 95% confidence interval; P value, probability value; IV, Inverse Variance methods; SE, standard error; SSI, surgical site infection.
Treatment-related risk factors
Laparoscopic surgery
A meta-analysis of 3 studies (10,17,24) showed that patients who did not undergo selective laparoscopic colorectal cancer resection had a high incidence of SSIs (OR =1.75, 95% CI: 1.30–2.34, I2=42%; ).
Figure 10
The forest plot showed the relationship between laparoscopic surgery and the risk of SSI. 95% CI, 95% confidence interval; P value, probability value; IV, Inverse Variance methods; SE, standard error; SSI, surgical site infection.
The forest plot showed the relationship between laparoscopic surgery and the risk of SSI. 95% CI, 95% confidence interval; P value, probability value; IV, Inverse Variance methods; SE, standard error; SSI, surgical site infection.
Operation time
Nine studies (15,16,18,19,21,24,25,27,29) reported that operation time could increase the risk of SSIs when the patient underwent a procedure longer than 180 minutes (OR =2.05, 95% CI: 1.61–2.59, I2=69%; ).
Figure 11
The forest plot showed the relationship between operation time and the risk of SSI. 95% CI, 95% confidence interval; P value, probability value; IV, Inverse Variance methods; SE, standard error; SSI, surgical site infection.
The forest plot showed the relationship between operation time and the risk of SSI. 95% CI, 95% confidence interval; P value, probability value; IV, Inverse Variance methods; SE, standard error; SSI, surgical site infection.
Blood transfusion
A meta-analysis of 4 studies (18,19,22,27) showed that patients who received a perioperative blood transfusion had a higher risk of SSIs (OR =2.02, 95% CI: 1.48–2.77, I2=0%; ).
Figure 12
The forest plot showed the relationship between blood transfusion and the risk of SSI. 95% CI, 95% confidence interval; P value, probability value; IV, Inverse Variance methods; SE, standard error; SSI, surgical site infection.
The forest plot showed the relationship between blood transfusion and the risk of SSI. 95% CI, 95% confidence interval; P value, probability value; IV, Inverse Variance methods; SE, standard error; SSI, surgical site infection.
Blood loss
Three studies (22,24,27) reported that patients had an increased risk of SSIs when they experienced blood loss of at least 100 mL (OR =1.38, 95% CI: 0.72–2.66, I2=80%; ).
Figure 13
The forest plot showed the relationship between blood loss and the risk of SSI. 95% CI, 95% confidence interval; P value, probability value; IV, Inverse Variance methods; SE, standard error; SSI, surgical site infection.
The forest plot showed the relationship between blood loss and the risk of SSI. 95% CI, 95% confidence interval; P value, probability value; IV, Inverse Variance methods; SE, standard error; SSI, surgical site infection.
Abdominal surgical history
Three studies (16,17,28) reported abdominal surgical history. The results revealed that patients who had a history of abdominal surgery might have higher risk of SSIs (OR =1.64, 95% CI: 1.18–2.28, I2=0%; ).
Figure 14
The forest plot showed the relationship between abdominal surgical history and the risk of SSI. 95% CI, 95% confidence interval; P value, probability value; IV, Inverse Variance methods; SE, standard error; SSI, surgical site infection.
The forest plot showed the relationship between abdominal surgical history and the risk of SSI. 95% CI, 95% confidence interval; P value, probability value; IV, Inverse Variance methods; SE, standard error; SSI, surgical site infection.
Ostomy formation
A meta-analysis of 3 studies (24,25,27) showed that patients with ostomy formation after colorectal cancer surgery had a lower incidence of SSIs (OR =0.74, 95% CI: 0.50–1.11, I2=0%; ).
Figure 15
The forest plot showed the relationship between ostomy formation and the risk of SSI. 95% CI, 95% confidence interval; P value, probability value; IV, Inverse Variance methods; SE, standard error; SSI, surgical site infection.
The forest plot showed the relationship between ostomy formation and the risk of SSI. 95% CI, 95% confidence interval; P value, probability value; IV, Inverse Variance methods; SE, standard error; SSI, surgical site infection.
Sensitivity analysis
We performed a sensitivity analysis to investigate heterogeneity in the included studies. The use of a fixed-effect model or a random-effects model did not significantly influence the merging direction of any risk factor (). Therefore, the data reported in this meta-analysis may be regarded as stable.
Table 4
Sensitivity analysis of the meta-analysis
Risk factors
Fixed-effects model
Random-effects model
Male gender
1.17 (1.12, 1.22)
1.20 (1.08, 1.35)
Obesity
1.18 (1.15, 1.21)
1.38 (1.20, 1.60)
diabetes mellitus
1.58 (1.44, 1.72)
1.58 (1.44, 1.72)
ASA score
1.72 (1.39, 2.12)
1.72 (1.39, 2.12)
Laparoscopic surgery
1.75 (1.30, 2.34)
1.95 (1.20, 3.16)
Cigarette smoking
1.35 (1.28, 1.43)
1.35 (1.28, 1.43)
Operation time
2.77 (2.69, 2.85)
2.05 (1.61, 2.59)
Age
0.98 (0.97, 0.99)
0.98 (0.93, 1.03)
Blood loss
1.00 (1.00, 1.00)
1.38 (0.72, 2.66)
Blood transfusion
2.02 (1.48, 2.77)
2.02 (1.48, 2.77)
Tumor location
1.49 (1.20, 1.83)
1.16 (0.72, 1.86)
Serum albumin
3.36 (2.25, 5.02)
3.36 (2.25, 5.02)
Ostomy formation
0.74 (0.50, 1.11)
0.74 (0.50, 1.11)
Abdominal surgical history
1.64 (1.18, 2.28)
1.64 (1.18, 2.28)
Data was showed by OR (95% CI). ASA, American Society of Anesthesiologists; 95% CI, 95% confidence interval.
Data was showed by OR (95% CI). ASA, American Society of Anesthesiologists; 95% CI, 95% confidence interval.
Publication bias
Funnel plots of male gender and obesity were used to qualitatively evaluate publication bias (). The plots showed that there was publication bias in some analyses. Therefore, the evidence related to these factors should be updated to eliminate potential publication bias.
Figure 16
The funnel plot of male gender and obesity. OR, odds ratio; SE, standard error.
The funnel plot of male gender and obesity. OR, odds ratio; SE, standard error.
Discussion
This meta-analysis investigated patient- and treatment-related risk factors of SSI. The results showed that male gender, obesity, diabetes mellitus, an ASA score of more than 3, cigarette smoking, a serum albumin level higher than 2.5 g/dL, tumor location, an operation time longer than 180 minutes, perioperative blood transfusion, blood loss of at least 100 mL, and abdominal surgical history were important risk factors of SSI. However, laparoscopic colorectal cancer resection may be a protective factor against SSI. No heterogeneity between the included studies was found in the analyses of male gender, diabetes mellitus, ASA score, cigarette smoking, serum albumin level, blood transfusion, abdominal surgical history, laparoscopic colorectal cancer resection, or ostomy formation, which indicated that the results were stable.Our results showed that male patients had a higher risk of SSI than female patients. This may be related to the different fat distribution between men and women (30). The surgical procedure could be more difficult for male patients who have excess visceral fat and abdominal obesity, which may lead to SSI.Study has shown that obesity is a significant risk factor for SSI (30). In patients with obesity, the incision fat easily liquefies and forms a dead cavity, which delays wound healing and can result in SSI. Other factors contributing to the increased risk of postoperative SSI in obese patients with colorectal cancer include decreased antibiotic concentration in the tissues, decreased blood oxygen tension in the surgical wounds, antibacterial penetration damage in perioperative tissues, extended operation time, increased intra-operative bleeding, and decreased immune function (30).Diabetes is a high-risk factor for postoperative infection in patients with colorectal cancer. Patients with diabetes have impaired glucose metabolism and glycolysis, which decreases the bactericidal function of neutrophils (31). In addition, the high sugar environment of wound effusion in patients with diabetes is more conducive to the growth and reproduction of bacteria. These factors increase the risk of infection in colorectal cancer patients with diabetes.ASA score is an indicator of the physical condition of a patient before surgery. In our study, ASA score was related to the risk of SSI (32), and patients with a higher ASA score had a higher incidence of SSI (33). Blood transfusion was also a risk factor for SSI in our study (34). Therefore, improving the skills of surgeons could decrease the blood loss of patients during surgery, which may reduce the risk of SSI.It has been reported that cigarette smoking can delay wound healing, which may lead to a risk of SSI. Our study found that patients who smoked had a higher risk of SSI in comparison with patients who did not smoke, which was consistent with the conclusions of the National Nosocomial Infections Surveillance System (NNIS) guidelines (35,36).Clinical study (36) has confirmed that surgical duration is a risk factor for SSI. The reasons for this are as follows: (I) the exposure of the surgical incision to air for a long time increases the chance of pathogen pollution; (II) the longer the operation time, the more complex the operation and the greater the trauma; and (III) prolonged anesthesia decreases immunity. Compared with traditional open surgery, laparoscopic surgery significantly reduces the exposure range of the incision, shortens the exposure time of abdominal organs to air, and decreases the opportunity for bacterial growth (37). This suggests that laparoscopic surgery could be a protective factor of SSI.Surgery is an important means of diagnosis and treatment for patients with colorectal cancer, but the occurrence of SSI is inevitable due to many factors. This study aimed to reduce the incidence of infection by identifying patients who may be at a higher risk of developing SSI and provide recommendations to reduce these risks.
Conclusions
This study identified 12 risk factors for SSI in patients with colorectal cancer, including male gender, obesity, diabetes mellitus, an ASA score greater than 3, tumor location, cigarette smoking, a serum albumin level of more than 2.5 g/dL, laparoscopic surgery, an operation time longer than 180 minutes, blood transfusion, blood loss of at least 100 mL, and an abdominal surgical history of SSI. These risk factors may provide a scientific basis for the prevention of SSI in patients with colorectal cancer.
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