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. 2022 Mar 28;17(3):e0264513. doi: 10.1371/journal.pone.0264513

Use of gentamicin-collagen sponge (Collatamp® G) in minimally invasive colorectal cancer surgery: A propensity score-matched study

Kil-yong Lee 1, Jaeim Lee 1,*, Youn Young Park 1, Seong Taek Oh 1
Editor: Robert Jeenchen Chen2
PMCID: PMC8959166  PMID: 35344540

Abstract

Background

Minimally invasive surgery is commonly used to treat patients with colorectal cancer, although it can cause surgical site infections (SSIs) that can affect the oncologic outcome. Use of a gentamicin-collagen sponge may help reduce the occurrence of SSIs. We aimed to determine the effectiveness of a gentamicin-collagen sponge in reducing SSIs in minimally invasive surgery for colorectal cancer.

Methods

We retrospectively reviewed the records of 310 patients who were diagnosed with colorectal cancer at our hospital and underwent minimally invasive surgery between December 1, 2018, and February 28, 2021. Propensity score matching was conducted with a 1:1 ratio using logistic regression. The primary outcome was the incidence of SSIs in the mini-laparotomy wound. The secondary endpoints were factors affecting the incidence of SSIs.

Results

After propensity score matching, 130 patients were assigned to each group. There were no differences in clinical characteristics between the two groups. SSIs occurred in 2 (1.5%) and 3 (2.3%) patients in the gentamicin-collagen sponge and control groups, respectively (p<0.999). The following factors showed a statistically significant association with SSIs: body mass index >25 kg/m2 (odds ratio, 39.0; 95% confidence interval, 1.90–802.21; p = 0.018), liver disease (odds ratio, 254.8; 95% confidence interval, 10.43–6222.61; p = 0.001), and right hemicolectomy (odds ratio, 36.22; 95% confidence interval, 2.37–554.63; p = 0.010).

Conclusion

Applying a gentamicin-collagen sponge to the mini-laparotomy wound did not reduce the frequency of SSIs. Further studies should be conducted on whether the selective use of gentamicin-collagen sponges may help reduce SSIs in high-risk patients.

Introduction

In patients with colorectal cancer, minimally invasive surgery reduces the hospital stay after surgery and increases patient satisfaction by reducing the incision area. A recent meta-analysis showed that minimally invasive surgery decreased the frequency of surgical site infections (SSIs) from 8.0% to 5.8% compared to open surgery (risk ratio: 0.72, 95% confidence interval [CI] 0.60–0.88) [1]; however, minimally invasive techniques cannot definitively prevent SSIs in colorectal as these are clean-contaminated operations.

The effectiveness of the gentamicin-collagen sponge in reducing SSIs has been reported in various fields of surgery, such as thoracic and orthopedic surgery [2, 3]. However, in the colorectal surgery field, a large-scale randomized control study [4] of gentamicin-containing sponges failed to prove their effectiveness. Nevertheless, a recent meta-analysis that excluded this study due to high risk of bias reported that, based on sensitivity analyses of abdominal wounds, gentamicin-collagen sponges could reduce the risk of SSI (relative risk [RR], 0.38; 95% CI, 0.20–0.72) [5].

For colorectal cancer patients, preventing SSI is important as they can affect long-term survival [6]. Few studies on whether gentamicin-collagen sponges (especially Collatamp® G (Schering-Plough, Stockholm, Sweden)) can prevent SSIs in laparoscopic colorectal cancer surgery have been performed. Therefore, we aimed to investigate the incidence of SSI after laparoscopic colorectal cancer surgery when using the Collatamp.

Materials and methods

This study was approved by the institutional review board (IRB) of the Catholic University of Korea (IRB number: UC21RISI0027). The study was performed in accordance with the relevant guidelines and regulations of the IRB. The investigation conformed with the principles outlined in the Declaration of Helsinki of 1964. Informed consent for participation was waived under IRB approval from the institutional review board of the Catholic University of Korea.

Patients

We enrolled patients who were diagnosed with colorectal cancer at our hospital and underwent minimally invasive surgery from December 1, 2018, to February 28, 2021. The prospectively collected database was analyzed retrospectively. Patients who underwent primary tumor resection via a laparoscopic or robotic approach were included in the study. The inclusion criteria were laparoscopic or robotic operations for biopsy-proven colorectal cancer and specimen extraction via mini-laparotomy wounds. The exclusion criteria were as follows: (1) open surgery, including conversion from laparoscopy; (2) transanal local resection or abdominoperineal resection for rectal cancer; (3) Hartmann’s operation; (4) laparoscopic biopsy only; and (5) early postoperative mortality within 7 days.

Procedure

The bowel was prepared using a polyethylene glycol electrolyte solution (4L; CoLyte; Taejoon Pharma Co., Ltd, Seoul, Korea) if the patient had no signs of complete obstruction or perforation, and oral antibiotics for bowel preparation had not been administered before surgery. One hour preoperatively, intravenous cefoxitin 2 g was administered for prophylaxis against infection. Specimen extraction or anastomosis was performed with an additional mini-laparotomy of approximately 5 cm for all patients. For right and left hemicolectomy, an extracorporeal anastomosis was performed using a mini-laparotomy in the upper midline and left upper quadrant, respectively. For an anterior or low anterior resection, after performing an intracorporeal rectal transection, a transverse incision was created in the left lower quadrant to extract the colon and resect it with appropriate margins followed by an intracorporeal end-to-end anastomosis. Dual-ring wound protectors were used for all mini-laparotomy wounds. After closing the abdominal wall fascia, a gentamicin-collagen sponge [Collatamp®G (Schering-Plough, Stockholm, Sweden); 5 cm × 5 cm, containing 50 mg gentamicin] was inserted in the subcutaneous layer.

Definitions

In our study, we focused on SSIs at the mini-laparotomy wound because we aimed to determine the effectiveness of the Collatamp® G in preventing SSIs. An SSI was defined as a clinically reported infection of the mini-laparotomy wound occurring within 30 days of the surgery according to the Center for Disease Control and Prevention (CDC) guidelines [7].

Liver disease was defined as the presence of hepatitis B or C, or any form of liver cirrhosis.

Sealed-off perforation was defined as a perforation with a localized abscess on the preoperative computed tomography image or as an intraoperative field without free perforation (i.e., fecal contamination or dirty fluid collection in the peritoneal cavity). Microperforation was defined as postoperative pathologic findings of a perforation.

Partial obstruction was defined as inability of the colonoscope to enter an encircling lesion in a patient who could pass stool. Complete obstruction was defined as no stenting or inability to place a stent.

Progression-free survival was defined as the time from the date of surgery to the date of a diagnosis of recurrence, cancer progression, or death from any cause. The date of the last outpatient visit to the doctor in charge was the last follow-up day for progression-free survival. Overall survival was defined as the time from the date of the operation to the date of death from cancer or any cause. The last follow-up day for overall survival was the last outpatient visit to our hospital.

Outcomes

The primary outcome was the incidence of SSI in the mini-laparotomy wound. The secondary outcome were the factors that affected the development SSIs.

Statistical analysis

For comparisons between the two groups, categorized variables were analyzed using Fisher’s exact test, the chi-square test, and linear-by-linear association; while continuous variables were analyzed using the Mann–Whitney test and the Student t-test. Categorized variables were expressed as numbers and percentages. Continuous variables were expressed as mean ± standard deviation. To analyze the survival in the two groups, Kaplan–Meier curves with the log-rank test were used.

Propensity-scored matching with a 1:1 ratio, using logistic regression with the nearest-neighbor method, was conducted to match the two groups. Propensity score matching was conducted using the R package MatchIt (R version 3.2.2; R Foundation for Statistical Computing, Vienna, Austria) [8]. The variables included in the matching were age, sex, height, weight, body mass index (BMI), underlying diseases (e.g., diabetes, hypertension, cardiac disease, pulmonary disease, liver disease, cerebrovascular disease), American Society of Anesthesiologists physical status classification, smoking, alcohol use, cancer location, operation name, operation type (i.e., laparoscopy or robotic), combined resection, preoperative obstruction, preoperative perforation, emergency operation, preoperative hemoglobin level, preoperative albumin level, packed red blood cell transfusion (i.e., preoperative or intraoperative), tumor stage, T stage, N stage, and M stage.

For multivariable analysis of factors affecting SSIs, logistic regression with backward stepwise selection of factors with a p-value <0.2 in the univariable analysis was performed as previously described [9, 10]. SPSS v.21 (IBM Corporation, New York, NY, USA) was used to conduct the analysis. Differences with a p-value <0.5 were considered statistically significant.

Results

After excluding 75 patients who underwent open surgery, 343 patients who underwent minimally invasive surgery from December 1, 2018, to February 28, 2021 remained. Patients who had undergone abdominoperineal resection, a Hartmann operation, or laparoscopic biopsy were excluded. Among the remaining 312 patients whose specimens were extracted through the mini-laparotomy site, 2 were excluded because they died within 7 days after surgery. Therefore, 310 patients were ultimately analyzed for the development of SSIs (Fig 1). One hundred and thirty patients and 180 patients were in the Collatamp group and the control group, respectively. The clinical characteristics of the two groups are shown in Table 1. In terms of patient characteristics, there were significantly more cases of cardiac disease in the control group before propensity score-matching; however, as with most other characteristics, there was no difference in the rates of SSIs.

Fig 1. Flowchart of patient inclusion.

Fig 1

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Table 1. Patients’ characteristics before propensity score-matching.

Control group (n = 180) Collatamp sponge group (n = 130) p-value
Age (y) 67.7 ± 11.9 66.8 ± 11.6 0.503
Sex 0.755
 Male 109 (60.6%) 81 (62.3%)
 Female 71 (39.4%) 49 (37.7%)
Height (cm) 162.0 ± 9.2 160.9 ± 8.4 0.273
Weight (kg) 61.6 ± 11.8 61.6 ± 11.2 0.987
Body mass index (kg/m 2 ) 23.4 ± 3.6 23.7 ± 3.7 0.356
Underlying disease
 Hypertension 101 (56.1%) 77 (59.2%) 0.584
 Diabetes 56 (31.1%) 37 (28.5%) 0.615
 Cardiac disease 31 (17.2%) 9 (6.9%) 0.008
 Pulmonary disease 20 (11.1%) 8 (6.2%) 0.133
 Liver disease 11 (6.1%) 3 (2.3%) 0.112
 Cerebrovascular disease 19 (10.6%) 14 (10.8%) 0.952
 Chronic kidney disease 12 (6.7%) 8 (6.2%) 0.856
ASA classification 0.365
 1 16 (8.9%) 10 (7.7%)
 2 123 (68.3%) 99 (76.2%)
 3 41 (22.8%) 21 (16.2%)
Smoking 0.348
 Ex-smoker 22 (12.2%) 13 (7.7%)
 Current smoker 27 (15.0%) 17 (13.1%)
Alcohol <0.001
 Ex-alcoholic 2 (1.1%) 2 (1.5%)
 Current alcoholic 31 (17.2%) 5 (3.8%)
Hemoglobin (g/dL) 12.0 ± 2.4 12.0 ± 2.3 0.875
Albumin (g/dL) 4.0 ± 0.6 3.9 ± 0.5 0.087
Cancer location 0.215
 Cecum 5 (2.8%) 2 (1.5%)
 Appendix 1 (0.6%) 0
 Ascending colon 29 (16.1%) 28 (21.5%)
 Hepatic flexure 8 (4.4%) 9 (6.9%)
 Transverse colon 7 (3.9%) 12 (9.2%)
 Splenic flexure 4 (2.2%) 2 (1.5%)
 Descending colon 2 (1.1%) 5 (3.8%)
 Sigmoid colon 44 (24.4%) 29 (22.3%)
 Rectosigmoid 13 (7.2%) 4 (3.1%)
 Rectum 65 (36.1%) 38 (29.2%)
 Double primary 2 (1.1%) 1 (0.8%)
Obstruction 0.023
 None 122 (67.8%) 104 (80.0%)
 Partial 29 (16.1%) 14 (10.8%)
 Stent insertion 24 (13.3%) 10 (7.7%)
 Complete obstruction 5 (2.8%) 2 (1.5%)
Perforation 0.505
 None 165 (91.7%) 123 (94.6%)
 Microperforation 11 (6.1%) 6 (4.6%)
 Sealed-off perforation 4 (2.2%) 1 (0.8%)
Operation methods 0.086
 Right hemicolectomy 45 (25.1%) 51 (39.2%)
 Left hemicolectomy 7 (3.9%) 6 (4.6%)
 Anterior resection 70 (39.1%) 33 (25.4%)
 Low anterior resection 55 (30.7%) 38 (29.2%)
 Total or subtotal colectomy 2 (1.1%) 2 (1.5%)
Combined resection 0.898
 No 170 (94.4%) 122 (93.8%)
 Liver 1 (0.6%) 2 (1.5%)
 Uterus 2 (1.1%) 0
 Small bowel 1 (0.6%) 2 (1.5%)
 Stomach. 1 (0.6%) 0
 Gallbladder 1 (0.6%) 0
 Ovary 2 (1.1%) 3 (2.3%)
 Spleen 1 (0.6%) 0
 Bladder 1 (0.6%) 1 (0.8%)
Operation type 0.078
 Laparoscopic 168 (93.3%) 127 (97.7%)
 Robotic 12 (6.7%) 3 (2.3%)
Emergency operation 8 (4.4%) 4 (3.1%) 0.538
Transfusion
 Preoperative 17 (9.4%) 13 (10.0%) 0.870
 Intraoperative 25 (13.9%) 9 (6.9%) 0.053
Stage 0.362
 0 (Tis) 6 (3.3%) 2 (1.5%)
 1 45 (25.0%) 31 (23.8%)
 2 41 (22.8%) 27 (20.8%)
 3 62 (34.4%) 49 (37.7%)
 4 26 (14.4%) 21 (16.2%)
T stage 0.539
 Tis 6 (3.3%) 2 (1.5%)
 1 27 (15.0%) 20 (15.4%)
 2 21 (11.7%) 15 (11.5%)
 3 97 (53.9%) 72 (55.4%)
 4a 28 (15.6%) 17 (13.1%)
 4b 1 (0.6%) 4 (3.1%)
N stage 0.914
 0 95 (52.8%) 64 (49.2%)
 1 45 (25.0%) 43 (33.1%)
 2 40 (22.2%) 23 (17.7%)
M stage 0.782
 0 153 (85.0%) 109 (83.8%)
 1 27 (15.0%) 21 (16.2%)
Surgical site infection 6 (3.3%) 2 (1.5%) 0.475
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ASA, American Society of Anesthesiologists

After propensity score matching was conducted by correcting for covariables that affected the development SSI, 130 patients were assigned to each group. The two groups showed no significant differences in clinical characteristics (Table 2). SSIs occurred in 2 (1.5%) and 3 (2.3%) patients in the Collatamp and control groups, respectively, showing no statistically significant difference (p >0.999). The median length of hospital stay in the Collatamp and control groups was 6.7 days and 6.5 days, respectively, which was not significantly different (p = 0.568). The incidence of postoperative complications, based on the Clavien-Dindo classification, was not significantly different (p = 0.546). Over an average follow-up period of 324 days, the estimated 2-year progression-free survival was higher in the Collatamp group (92.2%) than in the control group (77.3%); however, the difference was not significant (log-rank p-value = 0.092) (Fig 2). Similarly, over an average follow-up period of 347 days, there was no significant difference in estimated 2-year overall survival between the Collatamp group (94.8%) and the control group (92.7%; log-rank p-value = 0.581) (Fig 3).

Table 2. Patients’ characteristics after propensity score matching.

Control group (n = 130) Collatamp sponge group (n = 130) p-value
Age (y) 66.7 ± 12.0 66.8 ± 11.6 0.966
Sex 0.703
 Male 78 (60.0%) 81 (62.3%)
 Female 52 (40.0%) 49 (37.7%)
Height (cm) 161.3 ± 8.8 160.9 ± 8.4 0.716
Weight (kg) 61.4 ± 10.6 61.6 ± 11.2 0.874
BMI (kg/m 2 ) 23.5 ± 3.3 23.7 ± 3.7 0.638
Underlying disease
 Hypertension 72 (55.4%) 77 (59.2%) 0.531
 Diabetes 36 (27.7%) 37 (28.5%) 0.890
 Cardiac disease 17 (13.1%) 9 (6.9%) 0.098
 Pulmonary disease 8 (6.2%) 8 (6.2%) >0.999
 Liver disease 5 (3.8%) 3 (2.3%) 0.722
 Cerebrovascular disease 15 (11.5%) 14 (10.8%) 0.844
 Chronic kidney disease 5 (3.8%) 8 (6.2%) 0.393
ASA classification 0.903
 1 13 (10.0%) 10 (7.7%)
 2 92 (70.8%) 99 (76.2%)
 3 25 (19.2%) 21 (16.2%)
Smoking 0.488
 Ex-smoker 14 (10.8%) 13 (7.7%)
 Current smoker 19 (14.6%) 17 (13.1%)
Alcohol use 0.131
 Ex-alcoholic 2 (1.5%) 2 (1.5%)
 Current alcoholic 11 (8.5%) 5 (3.8%)
Hemoglobin (g/dL) 12.1 ± 2.5 12.0 ± 2.3 0.667
Albumin (g/dL) 4.0 ± 0.5 3.9 ± 0.5 0.067
Cancer location 0.323
 Cecum 5 (3.8%) 2 (1.5%)
 Appendix 1 (0.8%) 0
 Ascending colon 20 (15.4%) 28 (21.5%)
 Hepatic flexure 6 (4.6%) 9 (6.9%)
 Transverse colon 6 (4.6%) 12 (9.2%)
 Splenic flexure 3 (2.3%) 2 (1.5%)
 Descending colon 2 (1.5%) 5 (3.8%)
 Sigmoid colon 28 (21.5%) 29 (22.3%)
 Rectosigmoid 10 (7.7%) 4 (3.1%)
 Rectum 48 (36.9%) 38 (29.2%)
 Double primary 1 (0.8%) 1 (0.8%)
Obstruction 0.334
 None 96 (73.8%) 104 (80.0%)
 Partial 19 (14.6%) 14 (10.8%)
 Stent insertion 13 (10.0%) 10 (7.7%)
 Complete obstruction 2 (1.5%) 2 (1.5%)
Perforation 0.518
 None 121 (93.1%) 123 (94.6%)
 Microperforation 7 (5.4%) 6 (4.6%)
 Sealed-off perforation 2 (1.5%) 1 (0.8%)
Operation type 0.500
 Laparoscopic 124 (95.4%) 127 (97.7%)
 Robotic 6 (4.6%) 3 (2.3%)
Emergency operation 5 (3.8%) 4 (3.1%) >0.999
Transfusion
 Preoperative 13 (10.0%) 13 (10.0%) >0.999
 Intraoperative 10 (7.7%) 9 (6.9%) 0.812
Operation methods 0.185
 Right hemicolectomy 34 (26.2%) 51 (39.2%)
 Left hemicolectomy 6 (4.6%) 6 (4.6%)
 Anterior resection 49 (37.7%) 33 (25.4%)
 Low anterior resection 40 (30.8%) 38 (29.2%)
 Total or subtotal colectomy 1 (0.8%) 2 (1.5%)
Combined resection 0.294
 No 125 (96.2%) 122 (93.8%)
 Liver 1 (0.8%) 2 (1.5%)
 Uterus 1 (0.8%) 0
 Small bowel 1 (0.8%) 2 (1.5%)
 Stomach 1 (0.8%) 0
 Ovary 0 3 (2.3%)
 Spleen 1 (0.8%) 0
 Bladder 0 1 (0.8%)
Operation time (min) 193.2 ± 60.9 179.7 ± 66.2 0.089
Surgical site infection 3 (2.3%) 2 (1.5%) >0.999
Clavien–Dindo classification 0.546
 0 108 (83.1%) 112 (86.2%)
 1 4 (3.1%) 4 (3.1%)
 2 13 (10.0%) 10 (7.7%)
 3a 4 (3.1%) 2 (1.5%)
 3b 1 (0.8%) 2 (1.5%)
Hospital stay (days) 6.7 ± 3.7 6.5 ± 2.4 0.568
Stage 0.607
 0 (Tis) 4 (3.1%) 2 (1.5%)
 1 31 (23.8%) 31 (23.8%)
 2 29 (22.3%) 27 (20.8%)
 3 46 (35.4%) 49 (37.7%)
 4 20 (15.4%) 21 (16.2%)
T stage 0.623
 Tis 4 (3.1%) 2 (1.5%)
 1 17 (13.1%) 20 (15.4%)
 2 17 (13.1%) 15 (11.5%)
 3 74 (56.9%) 72 (55.4%)
 4a 17 (13.1%) 17 (13.1%)
 4b 1 (0.8%) 4 (3.1%)
N stage 0.812
 0 67 (51.5%) 64 (49.2%)
 1 34 (26.2%) 43 (33.1%)
 2 29 (22.3%) 23 (17.7%)
M stage 0.865
 0 110 (84.6%) 109 (83.8%)
 1 20 (15.4%) 21 (16.2%)
Lymphatic invasion 35 (27.6%) 68 (52.3%) <0.001
Venous invasion 52 (40.9%) 46 (35.4%) 0.359
Perineural invasion 44 (34.6%) 48 (36.9%) 0.703
Adjuvant chemotherapy 70 (53.8%) 67 (51.5%) 0.709
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ASA, American Society of Anesthesiologists; BMI, body mass index

Fig 2. Progression-free survival between the Collatamp group and the control group.

Fig 2

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There was no significant difference in the estimated 2-year progression-free survival rate between the two groups (log-rank p-value = 0.092).

Fig 3. Overall survival between the Collatamp group and the control group.

Fig 3

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There was no significant difference in the estimated 2-year overall survival rate between the two groups (log-rank p-value = 0.581).

The univariable analysis for factors affecting SSI among all 310 patients revealed that liver disease (p = 0.004), perforation (p<0.001), and right hemicolectomy (p = 0.001) were all associated with the development of SSI (Table 3).

Table 3. Univariable analysis for factors that affect surgical site infection in the overall cohort (n = 310).

No SSI (n = 302) SSI (n = 8) p-value
Age (y) 67.2 ± 11.5 71.3 ± 18.4 0.220
Sex 0.715
 Male 186 (97.9%) 4 (2.1%)
 Female 116 (96.7%) 4 (3.3%)
BMI (kg/m 2 ) 0.120
 <25 205 (98.6%) 3 (1.4%)
 >25 97 (95.1%) 5 (4.9%)
Hypertension
 None 126 (95.5%) 6 (4.5%) 0.076
 Present 176 (98.9%) 6 (1.1%)
Diabetes
 None 212 (97.7%) 5 (2.3%) 0.700
 Present 90 (96.8%) 3 (3.2%)
Cardiac disease
 None 262 (97.0%) 8 (3.0%) 0.603
 Present 40 (100%) 0
Pulmonary disease
 None 275 (97.5%) 7 (2.5%) 0.535
 Present 27 (96.4%) 1 (3.6%)
Liver disease
 None 291 (98.3%) 5 (1.7%) 0.004
 Present 11 (78.6%) 3 (21.4%)
Cerebrovascular disease
 None 269 (97.1%) 8 (2.9%) >0.999
 Present 33 (100%) 0
Chronic kidney disease 0.417
 None 283 (93.7%) 7 (87.5%)
 Present 19 (6.3%) 1 (12.5%)
ASA classification 0.523
 1 24 (92.3%) 2 (7.7%)
 2 218 (98.2%) 4 (1.8%)
 3 60 (96.8%) 2 (3.2%)
Smoking 0.587
 Nonsmoker 227 (97.0%) 7 (3.0%)
 Ex-smoker 32 (100%) 0
 Current smoker 43 (97.7%) 1 (2.3%)
Alcohol 0.983
 Nonalcoholic 263 (97.4%) 7 (2.6%)
 Ex-alcoholic 4 (100%) 0
 Current alcoholic 35 (97.2%) 1 (2.8%)
Hemoglobin (g/dL) 0.148
 <12 135 (95.7%) 6 (4.3%)
 >12 167 (98.8%) 2 (1.2%)
Albumin (g/dL) 0.051
 <3.5 57 (93.4%) 4 (6.6%)
 >3.5 245 (98.4%) 4 (1.6%)
Obstruction 0.231
 None 223 (98.7%) 3 (1.3%)
 Partial 39 (90.7%) 4 (9.3%)
 Stent insertion 33 (97.1%) 1 (2.9%)
 Complete obstruction 7 (100%) 0
Perforation <0.001
 None 282 (97.9%) 6 (2.1%)
 Microperforation 20 (100%) 0
 Sealed-off perforation 3 (60.0%) 2 (40.0%)
Operation type >0.999
 Laparoscopic 287 (97.3%) 8 (2.7%)
 Robotic 15 (100%) 0
Emergency operation 0.274
 Elective 291 (98.4%) 7 (2.3%)
 Emergency 11 (91.7%) 1 (8.3%)
Transfusion
 Preoperative >0.999
  None 272 (97.1%) 8 (2.9%)
  Done 30 (100%) 0
 Intraoperative 0.215
  None 270 (97.8%) 6 (2.2%)
  Done 32 (94.1%) 2 (5.9%)
Collatamp sponge insertion 0.475
 No 174 (96.7%) 6 (3.3%)
 Yes 128 (98.5%) 2 (1.5%)
Operation methods 0.001
 Right hemicolectomy 89 (92.7%) 7 (7.3%)
 Left hemicolectomy 13 (100%) 0
 Anterior resection or low anterior resection 195 (99.5%) 1 (0.5%)
 Total or subtotal colectomy 5 (100%) 0
Combined resection >0.999
 None 284 (97.3%) 8 (2.7%)
 Done 18 (100%) 0
Operation time (min) 190.6 ± 66.3 201.8 ± 44.3 0.280
Stage 0.493
 0 (Tis) 8 (100%) 0
 1 76 (100%) 0
 2 65 (95.6%) 3 (4.4%)
 3 106 (95.5%) 5 (4.5%)
 4 47 (100%) 0
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ASA, American Society of Anesthesiologists; BMI, body mass index

The multivariable analysis of these factors revealed that BMI >25 kg/m2 [OR, 39.0; 95% confidence interval (CI), 1.90–802.21; p = 0.018], liver disease (OR, 254.8; 95% CI, 10.43–6222.61; p = 0.001), and right hemicolectomy (OR, 36.22; 95% CI, 2.37–554.63; p = 0.010) were independently associated with SSI (Table 4).

Table 4. Multivariable analysis for factors that affect surgical site infection.

Odds ratio 95% Confidence interval p-value
BMI >25 (kg/m 2 ) 39.02 1.90–802.21 0.018
Albumin <3.5 (g/dL) 4.75 0.60–37.84 0.142
Liver disease 254.76 10.43–6222.61 0.001
Any type of perforation 8.86 0.51–154.74 0.135
Operation methods 0.010
 AR/LAR Reference Reference
 Right hemicolectomy 36.22 2.37–554.63
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AR, anterior resection; BMI, body mass index; LAR, low anterior resection

A subgroup analysis of patients was performed with the factors that were statistically significant in the multivariable analysis. This analysis revealed that in patients with a BMI >25 kg/m2, the frequency of SSI was lower in the Collatamp group [2.2% (1/84 patients)] than in the control group (7.1% (4/56)] (OR, 0.29; 95% CI, 0.03–2.68; p = 0.375). In the right hemicolectomy group, the Collatamp group [3.9% (2/51 patients)] also exhibited fewer SSIs than the control group [11.1% (5/45 patients)] (OR, 0.33; 95% CI, 0.06–1.77; p = 0.247). However, the differences in these subgroups were not significant (Table 5).

Table 5. Subgroup analysis of surgical site infection in high-risk patients.

Control group Collatamp sponge group p-value
BMI (kg/m 2 )
 >25 4/56 (7.1%) 1/46 (2.2%) 0.375
 <25 2/124 (1.6%) 1/84 (1.2%) >0.999
Liver disease
 None 4/169 (2.4%) 1/127 (0.8%) 0.396
 Present 2/11 (18.2%) 1/3 (33.3%) >0.999
Operation methods
 AR/LAR 1/125 (0.8%) 0/71 (0%) >0.999
 Right hemicolectomy 5/45 (11.1%) 2/51 (3.9%) 0.247
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AR, anterior resection; BMI, body mass index; LAR, low anterior resection

Discussion

In our study, we found that applying the Collatamp® G to the subcutaneous layer of the specimen extraction site did not affect the incidence of SSI. Therefore, no statistically significant difference in the length of stay and oncological results was observed between the two groups. Furthermore, the frequency of SSI in the Collatamp group was lower than that in the control group in a subgroup analysis of factors that affected the occurrence of SSI; however, the difference was not statistically significant.

SSI increases hospital stays and medical costs [11]. Furthermore, it can also affect a patient’s quality of life [12]. Efforts are needed to reduce the incidence of SSIs in cancer patients are needed as they can also affect survival [13–15]. In particular, one study showed that in patients with colon cancer, the 5-year disease-free survival rate was significantly lower in patients with SSI (83%) than in those without (87%) [16]. Thus, various efforts to reduce SSIs are required.

To date, several reports have been published regarding the effects of the gentamicin-collagen sponge. In 2013, in a meta-analysis on the effect of gentamicin-collagen implants on SSIs in all surgical fields, Chang et al. [3] reported that the OR was 0.51 (95% CI, 0.33–0.77; p = 0.001). In another meta-analysis [2], the investigators reported that the RR in four randomized controlled trials (RCT) was 0.61 (95% CI, 0.39–0.98; p = 0.04) in reducing the sternal wound infection after inserting a gentamicin-collagen sponge into the sternal wound after heart surgery.

Various studies have also used investigated the gentamicin-collage sponge in colorectal surgery [4, 17, 18]. A large-scale RCT [4] that involved all colorectal operations performed in 54 countries failed to prove the hypothesis that the gentamicin-collagen sponge would reduce the frequency of SSI. Similarly, an RCT [18] that included 291 patients who underwent laparoscopic colorectal surgery at a single center also failed to prove the efficacy of the gentamicin-collagen sponge. However, in a recent meta-analysis [5], a sensitivity analysis of abdominal wounds revealed that a gentamicin-collagen sponge could reduce SSI in colorectal surgery (RR, 0.38; 95% CI, 0.20–0.72).

With regard to this debate, we conducted a study to investigate whether the gentamicin-collagen sponge could reduce SSIs, which may affect the oncologic outcome of colon and rectal cancer; however, our study also failed to prove its efficacy.

The reason we could not demonstrate any difference between the two groups in our study was that the frequency of SSIs was low. The incidence of SSIs reported in large-scale RCTs [19–24] ranges from 3.7% to 8.9%. However, the incidence in our study was only 2.5%. This may be explained by our routine use of wound protectors. Dual-ring wound protectors have been widely used to significantly reduce SSI rates after elective surgery for colorectal cancer [25]. Another possible reason is that the sample size was insufficient for the application of the Collatamp to affect SSI. Even in the subgroup analysis, there was no significant difference between the Collatamp and control groups, which may have been due to the small sample size.

The effect of obesity on SSIs in laparoscopic colon surgery has already been demonstrated in other studies [26–28]. A meta-analysis by He et al. [28] revealed that overweightness was associated with an increased risk of SSI compared to normal weight (OR, 1.56; 95% CI 1.36–1.78; p < 0.001). Unlike in Western countries, the BMI cut-off for defining obesity in Asia-Pacific countries is set at 25 kg/m2 [29]. In fact, in our study, there were only 8 patients with a BMI of 30 kg/m2, none of which developed an SSI. Therefore, we also used the 25 kg/m2 cut-off to define obesity. Among obese patients with a BMI of ≥25 kg/m2, the incidence of SSI was significantly increased with an OR of 39.0 (95% CI, 1.90–802.21; p = 0.018). In particular, in the subgroup analysis, when the Collatamp was used in the BMI>25 kg/m2 group, the incidence of SSIs were reduced, with an OR of 0.29 (95% CI, 0.03–2.68; p = 0.375), compared with that in patients with a BMI<25 kg/m2; however, this difference was not statistically significant. This finding implied that the Collatamp sponge would be effective in obese patients.

When reviewing the current literature, there are few studies comparing SSIs in laparoscopic procedures such as laparoscopic right hemicolectomy or low anterior resection. Konish et al reported that the frequency of SSI was significantly higher in low anterior resection (9.5%) than in right hemicolectomy (7.5%) (p<0.001) [30]. Similarly, Degrate et al also reported that rectal surgery led to more frequent SSIs than right colonic surgery (17.6% vs 8.0%, p = 0.049) [31]. However, these studies also included open surgery. Our routine use of end-to-side anastomoses during right hemicolectomy may explain the high SSIs rates observed with this procedure in our study, where wound contamination may have occurred due to fecal spillage during insertion and withdrawal of the circular stapler through the incision. Since fecal contamination occurs when the anvil is inserted, the chances of wound contamination are lower in anterior or low anterior resection than in right hemicolectomy, which requires inserting and removing a circular stapler.

Limitations

The first limitation of our study is its retrospective, single-center design. Because of the retrospective study design, there was a possibility of selection bias. Furthermore, the single-center setting means that our results cannot be generalized. The second limitation is that the sample size was too small to prove the efficacy of the Collatamp in laparoscopic surgery. The inadequate sample size might lead to insufficient interpretation of the study results. As mentioned previously, the lack of a sufficient sample seems to underlie the inability to confirm statistical significance, even after subgroup analysis. When the sample size was calculated based on the results of our study, 1,134 participants were needed in each group. However, when the sample size was calculated based on the results of the right hemicolectomy group, only 209 patients were needed in each group. Therefore, it would be helpful to conduct multicenter studies focusing on this high-risk group in the future.

Conclusion

We demonstrated that, in patients with colon or rectal cancer who undergo minimally invasive surgery, applying a gentamicin-collage sponge to the mini-laparotomy wound did not reduce the frequency of SSIs, even in high-risk patients. However, since the possibility of a negative result due to the small sample size cannot be excluded, further multicenter RCTs should be conducted to determine whether the selective use of the gentamicin-collagen sponge may help reduce SSIs in patients at high risk.

Data Availability

Our data from this study are available upon request owing to the restrictions (data contain potentially identifying information [birth dates]) by the Institutional Review Board of Uijeongbu St. Mary’s Hospital, The Catholic University of Korea, South Korea. Please contact our IRB committee for data access via e-mail (irbujb@catholic.ac.kr).

Funding Statement

The authors received no specific funding for this work.

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Decision Letter 0

Robert Jeenchen Chen

10 Jun 2021

PONE-D-21-14973

Use of Gentamicin-Collagen Sponge (Collatamp® G) in laparoscopic colorectal cancer surgery: A propensity score-matched study

PLOS ONE

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Reviewer #1: Authors aim to determine the effectiveness of a gentamicin-collagen sponge to reduce surgical site infections in minimally invasive surgery for colorectal cancer in a single institution between December 1, 2018 and February 28, 2021. After propensity score matching, 130 patients were allocated to each group. No differences in clinical characteristics existed between the two groups. Surgical site infection occurred in 2 (1.5%) patients and 3 (2.3%) patients in the gentamicin-collagen sponge group and the control group, respectively (p<0.999). After analyzing factors that affect surgical site infection, the following factors were found to be statistically significant: body mass index >25 kg/m2 (odds ratio, 39.0; 95% confidence interval, 1.90-802.21; p=0.018), liver disease (odds ratio, 254.8; 95% confidence interval, 10.43-6222.61; p=0.001), and right hemicolectomy (odds ratio, 36.22; 95% confidence interval, 2.37-554.63; p=0.010). In summary, the present study indicated that applying a gentamicin-collagen sponge to mini-laparotomy wound could not reduce the frequency of surgical site infection. Further studies should be conducted regarding whether the selective use of gentamicin-collagen sponges may help reduce surgical site infection in high-risk patients. The results seems informative and appealing; however, there are a lot of criticisms and have several issues that the authors need to address before the manuscript is suitable for publication.

Major Compulsory Revisions:

1. The major flaw of the current study was that authors included only 260 patients divided into 2 groups (130 patients in each group), and the relatively low incidence of SSI (1.5% vs 2.3%); therefore, an estimated sample size analysis is warranted before authors conducting this study to prevent small sample size study bias.

2. In Patients paragraph: The inclusion criteria were laparoscopic or robotic operations for biopsy-proven colorectal cancer and specimen extraction via minilaparotomy wounds. However, the title of the manuscript is Use of Gentamicin-Collagen Sponge (Collatamp® G) in laparoscopic colorectal cancer surgery: A propensity score-matched study. The title needs to be amended.

3. In Statistical analysis paragraph: For multivariable analysis of factors affecting SSI, a logistic regression test was used for factors with a p-value <0.2 in univariable analysis. Authors have to elucidate why set a p-value <0.2 not < 0.05 to reduce false positives.

4. Another major flaw was that authors define body mass index >25 kg/m2 (overweight) as a variable for further analysis, of which it was relatively lower threshold compared to the common definition of obesity was BMI > 30 kg/m2. It would be better to re-analyze by using BMI > 30 kg/m2in the subsequent study.

5. Body mass index >25 kg/m2 (p=0.018), liver disease (p=0.001), and right hemicolectomy (p=0.010) were independent factors affecting SSI. The definitions of liver disease should be clarified with more detailed information, and how about uremia patients undergoing hemodialysis?

6. In Table 2: Total patients with surgical site infection was 5; however, there were 8 SSI in Table 3. The inconsistent data within the manuscript rise a serious concern.

7. Obviously, dual-ring wound protector has been widely used to significantly reduce SSI after elective surgery for colorectal cancer, e.g. Impact of a Dual-Ring Wound Protector on Outcome after Elective Surgery for Colorectal Cancer. J Surg Res 2019;244:136-145. There were no relevant references in the Discussion section.

8. In Discussion, right hemicolectomy was an independent factors affecting SSI should be described in more details with references.

9. In Conclusion paragraph: We demonstrated that in patients with colon cancer or rectal cancer who undergo laparoscopic resection, applying a gentamicin-collage sponge to the mini-laparotomy wound could not reduce the frequency of SSI. However, our findings confirmed that the gentamicin collagen sponge lowered the frequency of SSI among patients at high risk for SSI, although this difference was not statistically significant. The above statements must be extensively revised based on a negative results and no powerful data to demonstrate it.

Minor Essential Revisions:

1. Please correct the typo and grammatical error with an expert good at English-editing.

2. The term of operation name in tables 1-4 that is advised to be substituted with operation methods. .

Reviewer #2: The aim of the manuscript focus on the effect of Gentamicin-Collagen Sponge (Collatamp® G) in the SSI of laparoscopic colorectal surgery. It is interesting and important issue although the result of the study was limited due to small sample size. I have some comments for the authors.

1. What is the definition of the SSI in the study?

2.In methods, for multivariable analysis of factors affecting SSI, a logistic regression test was used for factors with a p-value <0.2 in univariable analysis. But Table 4 didn't show the multivariable analysis result of Hypertension and hemoglobin with p-value< 0.2 in univariable analysis.

3. In discussion, authors thought small sample size was the limitation for less SSI in this study than other previously published data. Please explain why subgroup analysis can compensate for the limitation.

4.Please explain the sentences "In particular, in the subgroup analysis, when the Collatamp was used in the BMI>25 kg/m 2 group, SSI was lowered by an OR of 0.29 (95% CI, 0.03-2.68; p=0.375), compared with that in patients with a BMI<25 kg/m2" in discussion. The data didn't show in result. Table 5 only showed Collatamp decrease SSI rate in BMI>25 kg/m2 (p=0.375).

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Reviewer #2: No

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PLoS One. 2022 Mar 28;17(3):e0264513. doi: 10.1371/journal.pone.0264513.r002

Author response to Decision Letter 0

16 Jun 2021

Reviewer #1: Authors aim to determine the effectiveness of a gentamicin-collagen sponge to reduce surgical site infections in minimally invasive surgery for colorectal cancer in a single institution between December 1, 2018 and February 28, 2021. After propensity score matching, 130 patients were allocated to each group. No differences in clinical characteristics existed between the two groups. Surgical site infection occurred in 2 (1.5%) patients and 3 (2.3%) patients in the gentamicin-collagen sponge group and the control group, respectively (p<0.999). After analyzing factors that affect surgical site infection, the following factors were found to be statistically significant: body mass index >25 kg/m2 (odds ratio, 39.0; 95% confidence interval, 1.90-802.21; p=0.018), liver disease (odds ratio, 254.8; 95% confidence interval, 10.43-6222.61; p=0.001), and right hemicolectomy (odds ratio, 36.22; 95% confidence interval, 2.37-554.63; p=0.010). In summary, the present study indicated that applying a gentamicin-collagen sponge to mini-laparotomy wound could not reduce the frequency of surgical site infection. Further studies should be conducted regarding whether the selective use of gentamicin-collagen sponges may help reduce surgical site infection in high-risk patients. The results seem informative and appealing; however, there are a lot of criticisms and have several issues that the authors need to address before the manuscript is suitable for publication.

Major Compulsory Revisions:

1. The major flaw of the current study was that authors included only 260 patients divided into 2 groups (130 patients in each group), and the relatively low incidence of SSI (1.5% vs 2.3%); therefore, an estimated sample size analysis is warranted before authors conducting this study to prevent small sample size study bias.

We sincerely appreciate the reviewer’s valuable comments. As mentioned in the discussion of the study’s limitations, the sample size required was calculated at about 1134 patients in each group, which is practically impossible to achieve with a single center retrospective design. In addition, since the purpose of this study was to conduct a randomized control study using Collatamp, a subsequent multicenter study will be conducted based on this study.

2. In Patients paragraph: The inclusion criteria were laparoscopic or robotic operations for biopsy-proven colorectal cancer and specimen extraction via minilaparotomy wounds. However, the title of the manuscript is Use of Gentamicin-Collagen Sponge (Collatamp® G) in laparoscopic colorectal cancer surgery: A propensity score-matched study. The title needs to be amended.

In accordance with the reviewer’s comment, we have changed the title.

Original:

Use of Gentamicin-Collagen Sponge (Collatamp® G) in laparoscopic colorectal cancer surgery: A propensity score-matched study

Revised:

Use of Gentamicin-Collagen Sponge (Collatamp® G) in minimally invasive colorectal cancer surgery: A propensity score-matched study

3. In Statistical analysis paragraph: For multivariable analysis of factors affecting SSI, a logistic regression test was used for factors with a p-value <0.2 in univariable analysis. Authors have to elucidate why set a p-value <0.2 not < 0.05 to reduce false positives.

We adopted this approach since in previous studies (1,2) multivariable analysis was also performed using variables with p <0.2 in the univariable analysis. We have clarified this in the revised Methods section.

References

1. Nakamura T, Sato T, Takayama Y, Naito M, Yamanashi T, Miura H, et al. Risk Factors for Surgical Site Infection after Laparoscopic Surgery for Colon Cancer. Surg Infect (Larchmt). 2016;17(4):454-8.

2. Hou TY, Gan HQ, Zhou JF, Gong YJ, Li LY, Zhang XQ, et al. Incidence of and risk factors for surgical site infection after colorectal surgery: A multiple-center prospective study of 3,663 consecutive patients in China. Int J Infect Dis. 2020;96:676-81.

4. Another major flaw was that authors define body mass index >25 kg/m2 (overweight) as a variable for further analysis, of which it was relatively lower threshold compared to the common definition of obesity was BMI > 30 kg/m2. It would be better to re-analyze by using BMI > 30 kg/m2in the subsequent study.

The cut-off for obesity in Asia-Pacific countries is different than that in Western countries, being only 25 kg/m2 (1). In fact, in our study, there were only 8 patients with a BMI of 30 kg/m2, none of which developed an SSI. Therefore, we also used the 25 kg/m2 cut-off to define obesity. We have addressed this issue in the revised Discussion.

Reference

1. Pan WH, Yeh WT. How to define obesity? Evidence-based multiple action points for public awareness, screening, and treatment: an extension of Asian-Pacific recommendations. Asia Pac J Clin Nutr. 2008;17(3):370-4.

5. Body mass index >25 kg/m2 (p=0.018), liver disease (p=0.001), and right hemicolectomy (p=0.010) were independent factors affecting SSI. The definitions of liver disease should be clarified with more detailed information, and how about uremia patients undergoing hemodialysis?

Liver disease was defined as hepatitis B, hepatitis C, or any form of liver cirrhosis. We have added this to the Methods section.

In accordance with the reviewer’s comment, we performed a re-analysis to include data regarding chronic kidney disease. There was no difference between the control and Collatamp groups. Furthermore, chronic kidney disease was not a risk factor for surgical site infection. We have added these results to the tables.

6. In Table 2: Total patients with surgical site infection was 5; however, there were 8 SSI in Table 3. The inconsistent data within the manuscript rise a serious concern.

Table 2 shows the patients after propensity score matching and Table 3 shows all patients before matching; therefore, the numbers are different. To avoid confusion, we have revised the title of Table 3.

7. Obviously, dual-ring wound protector has been widely used to significantly reduce SSI after elective surgery for colorectal cancer, e.g. Impact of a Dual-Ring Wound Protector on Outcome after Elective Surgery for Colorectal Cancer. J Surg Res 2019;244:136-145. There were no relevant references in the Discussion section.

Indeed, wound protectors were used for all mini-lap wounds in our study, which we believe may have resulted in fewer surgical site infections. We have added this point to the revised Discussion.

8. In Discussion, right hemicolectomy was an independent factors affecting SSI should be described in more details with references.

Thank you for your comment. When reviewing the current literature, there are few studies comparing SSIs in laparoscopic procedures such as laparoscopic right hemicolectomy or low anterior resection. Konish et al reported that the frequency of SSIs was significantly higher in low anterior resection (9.5%) than in right hemicolectomy (7.5%) (p<0.001). (30) Similarly, Degrate et al also reported that rectal surgery led to more frequent SSI rates than right colonic surgery (17.6% vs 8.0%, p=0.049)(31). However, these studies also included open surgery. Our routine use of end-to-side anastomoses during right hemicolectomy may explain the high SSIs rates observed with this procedure in our study, where wound contamination may have occurred due to fecal spillage during insertion and withdrawal of the circular stapler through the incision. Since fecal contamination occurs when the anvil is inserted, the chances of wound contamination are lower in anterior or low anterior resection than in right hemicolectomy, which requires inserting and removing a circular stapler. I have added the information to the discussion now.

References

1. Konishi T, Watanabe T, Kishimoto J, Nagawa H. Elective colon and rectal surgery differ in risk factors for wound infection: results of prospective surveillance. Ann Surg. 2006;244(5):758-63.

2. Degrate L, Garancini M, Misani M, Poli S, Nobili C, Romano F, et al. Right colon, left colon, and rectal surgeries are not similar for surgical site infection development. Analysis of 277 elective and urgent colorectal resections. International Journal of Colorectal Disease. 2011;26(1):61-9.

9. In Conclusion paragraph: We demonstrated that in patients with colon cancer or rectal cancer who undergo laparoscopic resection, applying a gentamicin-collage sponge to the mini-laparotomy wound could not reduce the frequency of SSI. However, our findings confirmed that the gentamicin collagen sponge lowered the frequency of SSI among patients at high risk for SSI, although this difference was not statistically significant. The above statements must be extensively revised based on a negative results and no powerful data to demonstrate it.

We have revised the conclusion according to the reviewer's comment.

Minor Essential Revisions:

1. Please correct the typo and grammatical error with an expert good at English-editing.

The manuscript has been revised by a native English speaker provided through a professional academic editing service. The certificate of editing has been attached.

2. The term of operation name in tables 1-4 that is advised to be substituted with operation methods. .

We have revised the terminology according to the reviewer's suggestion.

Reviewer #2: The aim of the manuscript focus on the effect of Gentamicin-Collagen Sponge (Collatamp® G) in the SSI of laparoscopic colorectal surgery. It is an interesting and important issue although the result of the study was limited due to the small sample size. I have some comments for the authors.

1. What is the definition of the SSI in the study?

An SSI was defined as a clinically reported infection of the mini-laparotomy wound occurring within 30 days after surgery according to the Center for Disease Control and Prevention (CDC) guidelines [1].

Reference

1. Mangram AJ, Horan TC, Pearson ML, Silver LC, Jarvis WR. Guideline for Prevention of Surgical Site Infection, 1999. Centers for Disease Control and Prevention (CDC) Hospital Infection Control Practices Advisory Committee. Am J Infect Control. 1999;27(2):97-132; quiz 3-4; discussion 96.

2. In methods, for multivariable analysis of factors affecting SSI, a logistic regression test was used for factors with a p-value <0.2 in univariable analysis. But Table 4 didn't show the multivariable analysis result of Hypertension and hemoglobin with p-value< 0.2 in univariable analysis.

We performed logistic regression with backward stepwise selection of factors with a p-value <0.2 in the univariable analysis. Accordingly, hypertension and hemoglobin were eliminated during this process. We have described our approach in the revised Methods to prevent confusion.

3. In discussion, authors thought small sample size was the limitation for less SSI in this study than other previously published data. Please explain why subgroup analysis can compensate for the limitation.

Subgroup analysis of groups in which SSS was more common was performed to obtain more meaningful results confirming whether Collatamp affects the incidence SSI. However, as pointed out by the reviewer, the analysis may have produced skewed results. Therefore, we have removed mention of these analyses from the revised manuscript.

4. Please explain the sentences "In particular, in the subgroup analysis, when the Collatamp was used in the BMI>25 kg/m 2 group, SSI was lowered by an OR of 0.29 (95% CI, 0.03-2.68; p=0.375), compared with that in patients with a BMI<25 kg/m2" in discussion. The data didn't show in result. Table 5 only showed Collatamp decrease SSI rate in BMI>25 kg/m2 (p=0.375).

Since the OR was not statistically significant, we did not mention it in the Results. However, to avoid any confusion, we have added them to the revised Results section.

Decision Letter 1

Robert Jeenchen Chen

14 Dec 2021

PONE-D-21-14973R1Use of Gentamicin-Collagen Sponge (Collatamp® G) in minimally invasive colorectal cancer surgery: A propensity score-matched studyPLOS ONE

Dear Dr. Lee,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

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Kind regards,

Robert Jeenchen Chen, MD, MPH

Academic Editor

PLOS ONE

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: (No Response)

Reviewer #2: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: No

Reviewer #2: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

**********

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PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

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6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Major Compulsory Revisions:

1. The major flaw of the current study was that authors included only 260 patients

divided into 2 groups (130 patients in each group), and the relatively low incidence of

SSI (1.5% vs 2.3%); therefore, an estimated sample size analysis is warranted before

authors conducting this study to prevent small sample size study bias.

Reply: We sincerely appreciate the reviewer’s valuable comments. As mentioned in the

discussion of the study’s limitations, the sample size required was calculated at about

1134 patients in each group, which is practically impossible to achieve with a single

center retrospective design. In addition, since the purpose of this study was to conduct

a randomized control study using Collatamp, a subsequent multicenter study will be

conducted based on this study.

Query: Authors should mention in the limitations as the inadequate sample size might lead to min-interpretation of results.

Conclusion paragraph: We demonstrated that, in patients with colon or rectal cancer who undergo laparoscopic

resection, applying a gentamicin-collage sponge to the mini-laparotomy wound did not reduce

the frequency of SSIs, even in high-risk patients.

Authors were suggested to correct "who undergo laparoscopic resection" to "who undergo minimally invasive surgery".

Reviewer #2: The authors have responded to all previous comments appropriately. Small sample size is still be concerned.

**********

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Reviewer #1: No

Reviewer #2: No

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PLoS One. 2022 Mar 28;17(3):e0264513. doi: 10.1371/journal.pone.0264513.r004

Author response to Decision Letter 1

16 Dec 2021

Reviewer #1: Major Compulsory Revisions:

1. Query: Authors should mention in the limitations as the inadequate sample size might lead to min-interpretation of results.

Response: We appreciate the reviewer’s thoughtful comments. Accordingly, we have presented this as a limitation

2. Conclusion paragraph: We demonstrated that, in patients with colon or rectal cancer who undergo laparoscopic resection, applying a gentamicin-collage sponge to the mini-laparotomy wound did not reduce the frequency of SSIs, even in high-risk patients.

Authors were suggested to correct "who undergo laparoscopic resection" to "who undergo minimally invasive surgery".

Response: Accordingly, we have revised the manuscript to reflect your suggestion.

Attachment

Submitted filename: Response to the reviewers_final.docx

Click here for additional data file. (15.6KB, docx)

Decision Letter 2

Robert Jeenchen Chen

14 Feb 2022

Use of Gentamicin-Collagen Sponge (Collatamp® G) in minimally invasive colorectal cancer surgery: A propensity score-matched study

PONE-D-21-14973R2

Dear Dr. Lee,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

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Kind regards,

Robert Jeenchen Chen, MD, MPH

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

Reviewer #2: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: (No Response)

Reviewer #2: (No Response)

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: No

Acceptance letter

Robert Jeenchen Chen

18 Mar 2022

PONE-D-21-14973R2

Use of Gentamicin-Collagen Sponge (Collatamp® G) in minimally invasive colorectal cancer surgery: A propensity score-matched study

Dear Dr. Lee:

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org.

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Thank you for submitting your work to PLOS ONE and supporting open access.

Kind regards,

PLOS ONE Editorial Office Staff

on behalf of

Dr. Robert Jeenchen Chen

Academic Editor

PLOS ONE

Associated Data

    This section collects any data citations, data availability statements, or supplementary materials included in this article.

    Supplementary Materials

    Attachment

    Submitted filename: Response to the reviewers_final.docx

    Click here for additional data file. (15.6KB, docx)

    Data Availability Statement

    Our data from this study are available upon request owing to the restrictions (data contain potentially identifying information [birth dates]) by the Institutional Review Board of Uijeongbu St. Mary’s Hospital, The Catholic University of Korea, South Korea. Please contact our IRB committee for data access via e-mail (irbujb@catholic.ac.kr).

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