Risk Factors for Surgical Site Infection after Laparoscopic Surgery for Colon Cancer

Abstract

Background:

Surgical site infection (SSI) occurring as a complication after laparoscopic surgery for colon cancer causes patients pain and psychological stress, prolongs the hospital stay, and increases healthcare costs. The present study was designed to clarify the incidence of, and risk factors for, SSI after surgery for colon cancer.

Methods:

The study group comprised 670 patients (370 male and 300 female; mean age, 67 y) who underwent laparoscopic surgery for colon cancer in our hospital from January 2010 through April 2015. Univariate and multivariable analyses were performed for 13 risk factors potentially related to post-operative SSI, including gender, age, body mass index, diabetes mellitus, American Society of Anesthesiologists (ASA) score, tumor location, pre-operative hemoglobin concentration, pre-operative serum albumin concentration, operation time, bleeding volume, tumor diameter, pathological stage, and type of sutures used for surgical site closure.

Results:

Surgical site infection occurred in 27 (4%) of the 670 patients. There was no surgery-related death. Univariate analysis of risk factors for SSI showed that the incidence of SSI was substantially lower in patients in whom Triclosan-coated PDS Plus^® sutures were used for surgical site closure (1.8%, seven of 382 patients) than in those in whom Triclosan-uncoated PDS-II^™ sutures were used (6.9%, 20 of 288 patients; p = 0.0017). The incidence of SSI was substantially greater in patients who had diabetes mellitus (9.3%, seven of 75 patients) than in those who did not (3.4%, 20 of 595 patients; p = 0.0154). On multivariable analysis, only the non-use of triclosan-coated PDS Plus sutures was substantially related to SSI, with an odds ratio of 3.322 (p = 0.021) as compared with the use of triclosan-coated PDS Plus sutures.

Conclusions:

To prevent SSI after laparoscopic surgery for colon cancer, triclosan-coated PDS Plus sutures should be used for abdominal closure.

Elective surgery for colorectal cancer is a clean-contaminated operation, and the incidence of post-operative SSI ranges from 3% to 26% [1 –3]. Risk factors for post-operative SSI include a high body-mass index (BMI) [3], diabetes mellitus [4], decreased body weight [4], intra-operative blood transfusion [5], open surgery [6], not using triclosan-coated PDS Plus sutures for surgical site closure [7], and not performing high-pressure washing or dermal suturing of the surgical site at the time of closure [8,9]. The development of SSI causes patients pain, prolongs the hospital stay, and considerably increases healthcare costs. The present study was designed to clarify the incidence of, and risk factors for, SSIs in a series of patients who received standard laparoscopic surgery for colon cancer and standard perioperative care in the same hospital. In addition, we report the results of cultures performed to identify causative organisms of SSIs.

Patients and Methods

A total of 670 patients (370 male and 300 female) underwent laparoscopic surgery for primary single colon cancer in our hospital from January 2010 through April 2015 (Table 1). The mean age was 67 y (range, 26 to 91). Right colectomy was performed in 282 patients, left colectomy in 280 patients, and anterior colectomy in 108 patients. Patients were excluded from the study if they had received pre-operative chemotherapy, undergone emergency surgery, or were converted to open surgery. We studied the following 12 potential risk factors for SSI: Gender (male vs. female), age (<65 y vs. ≥65 y), BMI (kg/m²), American Society of Anesthesiologists (ASA) score (I vs. ≥II), presence or absence of diabetes mellitus, tumor location (cecum, ascending colon, transverse colon, descending colon, sigmoid colon, rectosigmoid), pre-operative hemoglobin concentration (<10 g/m² vs. ≥10 g/m²), pre-operative albumin concentration (<3.5 g/dL vs. ≥3.5 g/dL), operation time (<180 min vs. ≥180 min), bleeding volume (<50 mL vs. ≥50 mL), tumor diameter (<3.5 cm vs. ≥3.5 cm), pathological stage (I vs. ≥II), and type of sutures used for surgical site closure (triclosan-coated PDS Plus sutures vs. triclosan-uncoated PDS II sutures).

Table 1.

Demographic Characteristics of Patients

Gender	Male : Female	370 : 300
Age (y)		67 (26–91)
^*BMI (kg/m²)		23 (13–36)
^**ASA score	I : II : III	393 : 267 : 10
^***Tumor location	C : A : T : D : S : Rs	73 : 148 : 61 : 42 : 238 : 108
Surgical procedure	Illeocecal resection	23
	Right hemicolectomy	223
	Left hemicolectomy	78
	Sigmoidectomy	238
	Anterior resection	106
	Hartmann operation	2
pStage	0, I	229
	II	189
	III	211
	IV	41

BMI = body mass index; ^**ASA = American Society of Anesthesiologists; ^***tumor location; C = cecum; A = ascending colon; T = transverse colon; D = descending colon; S = sigmoid colon; Rs = rectosigmoid colon.

Surgical technique

A 12-mm port was initially placed in the umbilical region through a small abdominal incision and was used as a camera port in patients with right- or left-sided colon cancer. The colon was concurrently insufflated with carbon dioxide at a mean pressure of 8 mmHg/h to induce pneumoperitoneum. A 5-mm flexible scope was used to examine the abdominal cavity. Two ports each were then placed into the left and right sides of the middle lower abdomen. A total of five ports were thus used. In patients with right-sided colon cancer, the transection sites of the ileocolic artery, right colic artery, and middle colic artery were decided on the basis of the tumor location and disease stage. In patients with T3 or deeper tumors, the major blood vessels were transected at their origins. To perform transection and anastomosis, the small incision in the umbilicus was extended to about 5 cm, and the intestine was exteriorized through the incision. In patients who had left-sided colon cancer with T3 or deeper tumors, the inferior mesenteric artery was transected at its origin. Similar to patients with right-sided colon cancer, the small incision in the umbilicus was extended to 3 cm to 4 cm to transect and anastomose the intestine. If the intestine could not be elevated, the mesentery was widened, and the distal intestine was transected intra-corporeally, using an automatic suturing device. The lesion was exteriorized through a small incision, and the proximal intestine was transected. Then, the tip of an automatic suturing device was placed in the intestinal stump, which was then returned to the body. The abdomen was re-insufflated, and anastomosis was performed intra-corporeally by the double-stapling technique.

Perioperative care

All patients pre-operatively received mechanical bowel preparation (two sennoside tablets 2 d before surgery and one pack of magnesium citrate plus one bag of sodium picosulfate 1 d before surgery, given orally). No chemical bowel preparation was performed.

Administration of prophylactic antibiotics

To prevent post-operative infection, patients received 1 g of cefmetazole sodium, given as a continuous intravenous infusion. Cefmetazole was given once at the time of incision. Additional doses were subsequently given every 3 h. On the day after surgery, cefmetazole was given only once. This regimen was consistently used in the study population.

Methods for surgical site closure

For surgical site closure, the peritoneum and the fascia were closed together. Knotted sutures were placed, using triclosan-uncoated 0-PDS I suture (Johnson and Johnson K. K., Japan) from January 2010 through March 2012 and triclosan-coated 0-PDS Plus suture (Johnson and Johnson K. K., Japan) from April 2012 through April 2015. After suturing the fascia, the subcutaneous tissue was washed with 200 mL of warmed physiological saline solution, applied at high pressure. For dermal suture, 4-0 triclosan-uncoated PDS II suture was used from January 2010 through March 2012 (NP group), and 4-0 triclosan-coated PDS Plus suture was used from April 2012 through April 2015 (PP group), as described above. After abdominal closure, the surgical site was covered with polyurethane film dressing for 48 h after surgery. Subsequently, the surgical site was left uncovered. Disinfection was not performed.

Evaluation of surgical site infection

Surgical site infection was evaluated by surgeons (operators and others) and nurses (hospital and infection wards), who examined the surgical site. Surgical site infection was diagnosed according to the 1999 guidelines for the prevention of surgical-site infection (SSI) [10]. The presence of pus discharge was required for a diagnosis of SSI. Surgical site redness alone was excluded.

Post-operative follow-up

After discharge within 30 d after surgery, patients were followed up on an outpatient basis once every 2 to 4 wks. The surgical site infection was confirmed, and adjuvant chemotherapy began within 8 wks after surgery. Follow-up computed tomography (CT) of the chest and abdomen was performed every 6 mo after surgery. The pre-operative and post-operative courses of each patient were assessed by retrospectively reviewing the patient's medical records.

Statistical analysis

Statistical analysis was performed with the use of the Chi-square test with Yates' correction. Multivariable logistic regression analysis was performed for factors with p values of less than 0.2 on univariate analysis. P values of less than 0.05 were considered to indicate statistical significance. All analyses were performed using SPSS version 8.0J (SPSS, Inc., Chicago, Ill, USA).

Results

The incidence of SSI after laparoscopic surgery for colon cancer was 4% (27 of 670 patients). In our study, the rate of superficial SSI was 3.1% (21/670), the rate of deep SSI was 0.9% (6/670), and the rate of organ space infection was 3.6% (24/670). The rate of SSI was cecum 6.8% (5/73), ascending colon 6% (9/148), transverse colon 3.3% (2/61), descending colon 0% (0/42), sigmoid colon 4.2% (10/238), rectosigmoid colon 1% (1/108). There was no death. The mean post-operative hospital stay was 8.8 d (range, five to 40) in patients without SSI and 22.0 d (range, seven to 65) in patients with surgical infection. This difference was substantial (p = 0.0001). No patient had flare-ups of SSI or surgical site dehiscence during follow-up after discharge. Pus from the infected surgical sites was cultured in all patients with SSI, and cultures were positive for pathogens in 26 (96%) of the 27 patients with SSI (Table 2). The causative organisms were Bacteroides species in 14 patients (54%), Enterococcus faecalis in five (19%), and Enterobacter cloacae in three (12%). Surgical site infections occurred in 15 females, indicating a slightly greater proportion of females, and were most often associated with tumors located in the right side of the colon. The rate of SSI was 5.7% (16/282) after right-sided colectomy and 2.8% (11/388) after left-sided colectomy. Many patients with SSI underwent functional end-to-end anastomosis (FEEA). SSI was also frequently associated with an operation time of ≥180 min and advanced cancer with a pathological stage of ≥II.

Table 2.

Pathogens

Pathogen	n = 26
Bacteroides fragilis	5
Bacteroides thetaiotaomicron	5
Bacteroides valbatus	2
Bacteroides species	2
Bacteroides ovatus	1
Enterococcus faecalis	5
Enterobacter cloacae	2
Enterobacter oerogenes	1
Pseudomonas aeruginosa	2
Escherichia coli	1

On univariate analysis, the incidence of SSI was substantially greater in the NP group (6.9%, 20 of 288 patients) than in the PP group (1.8%, seven of 382 patients; p = 0.0017) and was substantially greater in patients with diabetes mellitus (9.3%, seven of 75 patients) than in those without diabetes mellitus (3.4%, 20 of 595 patients; p = 0.0303) (Table 3). On multivariable analysis including factors that had p values of 0.2 or less on univariate analysis (i.e., gender [female], an ASA score of ≥II, and a pre-operative hemoglobin concentration of <10 g/dL), only the NP group was an independent risk factor for SSI (p = 0.0012; odds ratio, 4.2667) (Table 4).

Table 3.

Risk Factors for Surgical Site Infection: Univariate Analysis

		Surgical site infection (+) (n = 27)	Surgical site infection (−) (n = 643)	p
Gender	Male : Female	12 : 15	385 : 285	0.2536
Age (y)	<65 : ≥65	7 : 20	235 : 408	0.3570
BMI(kg/m²)	<25 : ≥25	16 : 9	447 : 196	0.7144
ASA score	I : ≥II	12 : 15	381 : 262	0.1831
Tumor location	C, A, T, D : S, Rs	16 : 11	377 : 266	0.9482
Diabetes mellitus	+ : −	7 : 20	68 : 575	0.0303
Pre-hemoglobin (g/dL)	<10 : ≥10	6 : 21	76 : 567	0.1882
Pre-albumin (g/dL)	<3.5 : ≥3.5	6 : 21	78 : 565	0.2096
Operation time (min)	<180 : ≥180	10 : 17	236 : 407	0.9719
Bleeding (mL)	<50 : ≥50	23 : 4	528 : 115	0.9793
Tumor diameter (cm)	≦3.5 : ≥3.5	11 : 16	286 : 357	0.8530
pT	∼2 : 3∼	11 : 16	260 : 383	0.8491
pStage	∼I : I∼	6 : 21	223 : 420	0.2585
Suture	^PP:^*NP	20 : 7	268 : 375	0.0017

PP = PDS-Plus; ^**NP = non-PDS-Plus; pT = depth invasion of colon cancer.

Table 4.

Multivariable Analysis

	Odds ratio	95% CI	p
^*NP	4.2667	1.7685-10.2936	0.0012
Pre-hemoglobin ≥10 g/dL	1.9151	0.7279-5.0386	0.1880
ASA score ≥II	1.6935	0.7043-4.0723	0.2393
Diabetes mellitus (+)	1.3942	0.4513-4.3075	0.5636

NP = non PDS-Plus

CI = confidence interval; ASA = American Society of Anesthesiologists.

Discussion

In the present study, we examined the incidence of SSI after laparoscopic surgery for colon cancer in patients who consistently received standardized pre-operative and peri-operative care in a single hospital. The incidence of SSI was 4%, which was generally lower than that in previous studies (3% to 26% on average). As for independent risk factors, our study clearly demonstrated that the incidence of SSI was substantially lower in the PP group than in the NP group.

The incidence of SSI after laparoscopic surgery for colorectal cancer was reported to be 2.7% to 3.0% at the trocar site and 10.8% at the surgical site at the site where the intestine was exteriorized [11]. In our hospital, there were no infections at the trocar site, and the intestine was exteriorized via an incision in the umbilical region in all patients. The infection rate was 14%, which was lower than that in the previous studies described above. We therefore reported that intra-operative protection of the surgical site margin, high-pressure washing, and dermal suturing play important roles in preventing SSI [8,9]. The post-operative development of SSI extended the hospital stay by about 13 d on average, increasing medical costs by approximately 542 US dollars per patient.

Several studies have examined the relation between SSI and sutures and reported that antibacterial sutures, such as triclosan-coated sutures (triclosan-coated polydioxanone, PDS Plus, PDP771D; Ethicon Inc., USA) help to decrease the risk of SSI [12 –15]. Nakamura et al. conducted a randomized controlled trial designed to identify risk factors for post-operative SSI in 410 patients with colorectal cancer. The incidence of SSI was substantially lower in the triclosan-coated polydioxanone group (4.3%) than in the control group (9.3%, p = 0.047) [7]. This finding was consistent with the results of our study. However, the study by Nakamura et al. included 183 patients (45%) who underwent open surgery, which itself has been reported to be a risk factor for SSI.

Diener et al. conducted a randomized controlled trial (the PROUD trial, n = 1,185) and reported that the incidence of SSI did not differ substantially between patients who underwent abdominal surgical site closure with non-antibacterial uncoated PDS II sutures (16.1%) and those who underwent abdominal surgical site closure with antibacterial triclosan-coated PDS Plus sutures (14.8%) [16]. This finding is inconsistent with the results of our study. However, they studied patients who underwent elective abdominal surgery for any reason. In their series, only 403 patients (34%) had colon cancer. Although this was the largest subgroup of patients, we cannot accept these results without further qualification. In addition, although the fascia was closed with continuous triclosan-coated PDS Plus sutures, the skin was closed with staples, without suturing the dermis. This is a major difference from the closure technique used in our study. Moreover, a subgroup analysis of patients who underwent lower gastrointestinal surgery showed no difference in the incidence of post-operative SSI between the patients in whom triclosan-coated PDS Plus sutures were used (18.0%) and those in whom triclosan-uncoated PDS II sutures were used (17.3%) [17].

As for the relation between SSI and diabetes mellitus, the risk of SSI has yet to be accurately evaluated in patients with diabetes mellitus who underwent laparoscopic surgery for colorectal cancer. A study of post-operative SSI in 1144 patients who underwent cardiac surgery found no relation between post-operative SSI and pre-operative blood glucose concentrations or elevated hemoglobin A1c concentrations. However, hyperglycemia (200 g/dL) occurring within 48 h after surgery has been reported to increase the risk of post-operative SSI by two-fold [4,5]. In our hospital, the incidence of SSI among patients with diabetes mellitus has increased, despite strict control of serum blood glucose concentrations before and after surgery, suggesting that diabetes mellitus is directly associated with an increased risk of SSI.

Lewis et al. reported that common causative organisms of SSI after lower gastrointestinal surgery were Escherichia coli, streptococci, anaerobes, and bacteroides species. They therefore recommended the use of metronidazole [18]. In our study, cefmetazole was used as prophylactic antibacterial therapy against Bacteroides species, Enterococcus faecalis, and Enterobacter cloacae. In terms of tissue concentrations, treatment was given to maintain an MIC80 (drug concentration reducing growth by 80%), which probably led to the low incidence of SSI. In our study, the use of triclosan-coated PDS Plus sutures for surgical site closure was shown to substantial decrease the incidence of SSI.

Maintaining concentrations of cefmetazole at MIC80 or greater in serum and tissue against causative organisms such as E. coli, Klebsiella species, and Bacteroides species was found to be appropriate for antimicrobial prophylaxis. On the other hand, cefmetazole concentrations in subcutaneous adipose tissue were low. Therefore, antibacterial absorbable sutures (PDS Plus) should be used to prevent SSI because prophylactic antibacterial agents are unlikely to be distributed to subcutaneous adipose tissue at the time of surgical site closure.

In Japan, large randomized controlled trials are needed to confirm risk factors for SSI and thereby establish more effective prophylactic therapy.

Footnotes

Author Disclosure Statement

No competing financial interests exist.

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